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Patent Searching and Data


Title:
CONSTRUCTS RELATING TO GENETIC DISORDERS
Document Type and Number:
WIPO Patent Application WO/2024/081592
Kind Code:
A2
Abstract:
Polynucleotides, expression constructs, compositions, kits and method relating to genetic disorders are disclosed. Some embodiments provided herein encompass variants of a protein that relate to a genetic disorder. Also contemplated are expression constructs that encode highly functional and/or stable protein variants. Also described herein are expression constructs that encode protein variants with reduced activity and/or stability. Also described herein are compositions, kits and methods for diagnosing and treating the genetic disorder. In some embodiments, the variants can relate to the treatment and/or diagnosis of genetic disorders.

Inventors:
LO RUSSELL S (US)
CROMIE GARETH A (US)
DUDLEY AIMÉE M (US)
Application Number:
PCT/US2023/076379
Publication Date:
April 18, 2024
Filing Date:
October 09, 2023
Export Citation:
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Assignee:
PACIFIC NORTHWEST RES INSTITUTE (US)
International Classes:
C12N9/88; C12Q1/6883
Attorney, Agent or Firm:
LOZAN, Vladimir (US)
Download PDF:
Claims:
CLAIMS 1. A protein having the amino acid sequence of any one of the SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110. 2. A protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C. 3. The protein of claims 1-2, wherein the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C exhibits higher activity when compared to the WT protein of SEQ ID NO:1. 4. The protein of any of the preceding claims, wherein the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 5% when compared to the function of wild-type protein of SEQ ID NO:1.

5. The protein of any of the preceding claims, wherein the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10% when compared to the function of wild-type protein of SEQ ID NO:1. 6. The protein of any of the preceding claims, wherein the point mutants comprise at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351. 7. A protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C. 8. The protein of claim 7, wherein the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C exhibits higher activity when compared to the WT protein of SEQ ID NO:1. 9. The protein of claims 7-8, wherein the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10% when compared to the function of wild- type protein of SEQ ID NO:1.

10. The protein of claims 7-9, wherein the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 50% when compared to the function of wild- type protein of SEQ ID NO:1. 11. The protein of claims 7-10, wherein the point mutants comprise at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 53, 120, 124, 143, 211, 266, 324, 325, 326, 350. 12. An expression vector comprising a polynucleotide sequence encoding for one or more of the proteins in any one or more of claims 1-11. 13. The expression vector of claim 12, wherein the sequence is a codon-optimized sequence. 14. The expression vector of claim 13, wherein the polynucleotide sequence comprises one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 5% when compared to the function of wild-type protein of SEQ ID NO:1. 15. The expression vector of claim 13, wherein the polynucleotide sequence comprises one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of wild-type protein of SEQ ID NO:1.

16. A composition of any of the preceding claims, wherein the protein is ornithine transcarbamylase (OTC). 17. A composition of any of the preceding claims, for use in the treatment of a genetic disorder. 18. A composition of any of the preceding claims, wherein the composition is administered to a subject having a genetic disorder in an amount effective to correct the genetic disorder or a symptom thereof in the subject. 19. A composition of claims 16-18, wherein the genetic disorder is OTC deficiency. 20. A method of enhancing the functionality of Ornithine transcarbamylase (OTC) protein in a subject, the method comprising: administering to the subject the protein or composition of any one of claims 1- 19, wherein the OTC deficiency or a symptom thereof is reduced after administration. 21. The method of claim 20, wherein the subject is a fetus, neonate, juvenile or adult. 22. The method of claim 20, wherein one or more expression vectors is administered to a subject in an amount effective to correct the OTC deficiency or a symptom thereof in the subject. 23. The method of claim 20, wherein the OTC is modified to exhibit an enhanced function. 24. The method of claim 20, wherein the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 to exhibit an enhanced function. 25. The method of claim 20, wherein the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110. 26. The method of claims 20-25, wherein the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 5% when compared to the function of WT protein of SEQ ID NO:1. 27. The method of claims 20-25, wherein the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143Cis enhanced by at least 50% when compared to the function of WT protein of SEQ ID NO:1. 28. The method of claims 20-25, wherein the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of WT protein of SEQ ID NO:1. 29. A method of screening for a protein variant, the method comprising: a) providing a population of yeast strains each expressing a protein of claims 1-11; b) growing the yeast strains on a minimal growth medium; c) screening the population of yeast strains expressing the protein variant for growth based on a growth score; d) identifying the protein variant based on the growth score that was screened for; and e) identifying a specific region or a position with an amino acid substitution of the protein variant that was identified based on the growth score, wherein the growth score of the protein variant is higher than the growth score of the WT protein. 30. The method of claim 29, wherein the position with an amino acid substitution is further substituted with another amino acid. 31. A method of screening for a protein variant, the method comprising: a) providing a population of yeast strains each expressing a protein of claims 1-11; b) growing the yeast strains on a minimal growth medium; c) screening the population of yeast strains expressing the protein variant for growth based on a growth score; d) identifying the protein variants based on the growth score that was screened for; and e) functionally classifying the identified protein variants based on the growth score. 32. The method of claim 31, wherein the growth score of the protein variant is higher than the growth score of the WT protein, lower than the growth score of the WT protein, or the same as the growth score of the WT protein. 33. A kit for determining a specific mode of treatment of a genetic disorder comprising: a look up table, wherein the look up table indicates specific amino acid substitutions that are commonly involved in a cellular mechanism; and one or more vectors comprising sequences of SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110. 34. The kit of claim 33, wherein the look up table comprises a list of mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C.

35. The kit of claim 33, wherein the genetic disorder is OTC deficiency. 36. A method of identifying a subject having a genetic disorder, the method comprising: detecting a presence of at least one mutation in the protein that is different in the subject with a genetic disorder as compared to a subject without the disorder, wherein the presence of at least one mutation indicates the presence of a genetic disorder in the subject. 37. A method of improving, ameliorating, or treating a genetic disorder, the method comprising: detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject; and administering to the subject the protein or composition of any one of claims 1- 19, wherein the genetic disorder or a symptom thereof is reduced after administration. 38. The method of one of claims 36 or 37, wherein the mutation is selected from a group consisting of: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I. 39. The method of claims 36-38, wherein the genetic disorder is OTC deficiency. 40. The method of one of claims 36 or 37, wherein the one mutation that indicates the presence of genetic disorder in the subject is selected from the mutations in Table 3. 41. The method of claim 40, wherein an engineered protein administered to the subject includes one or more of the mutations in Table 2. 42. A variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1, selected from the group consisting of any one of the mutations: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L, wherein when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. 43. A variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351, wherein when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. 44. A composition of claims 42-43, wherein the protein is ornithine transcarbamylase (OTC). 45. A method for identifying a subject having a genetic disorder, the method comprising: detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder that exhibits dominant negative interactions with a wildtype protein of SEQ ID NO:1, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject. 46. A method of improving, ameliorating, or treating a genetic disorder, the method comprising: detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder that exhibits dominant negative interactions with a wildtype protein of SEQ ID NO:1, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject; and administering to the subject the protein or composition of any one of claims 1- 19, wherein the genetic disorder or a symptom thereof is reduced after administration. 47. The method of claim 45 or 46, wherein the subject is a fetus, neonate, juvenile or adult. 48. The method of claim 45-47, wherein the mutation is selected from R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L. 49. A kit for identifying proteins with specific amino acid substitutions comprising: a look up table, wherein the look up table indicates proteins with specific amino acid substitutions that exhibit dominant negative interactions with a wildtype protein of SEQ ID NO:1. 50. The kit of claim 49, wherein the look up table comprises a list of mutations as follows: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L. 51. A method of screening for a protein variant that exhibits dominant negative interactions with a wildtype protein, the method comprising: a) providing a population of haploid yeast strains each expressing a protein variant of claims 42-43; b) mixing the population of haploid yeast strains expressing the protein variant with a haploid yeast strain expressing a WT protein to generate a population of diploid yeast strains each expressing a variant protein in combination with the WT protein; c) growing the diploid yeast strains on a minimal growth medium; d) screening the population of diploid yeast strains expressing a variant protein in combination with the WT protein for growth based on a growth score; and e) identifying a protein variant that exhibits dominant negative interactions with a wildtype protein based on the growth score that was screened for. 52. The method of claim 51, wherein the minimal growth medium lacks arginine.

Description:
PNDRI.014WO PATENT APPLICATION CONSTRUCTS RELATING TO GENETIC DISORDERS CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims priority to United States Provisional Patent Application No. 63/379116, filed October 11, 2022, the entire contents of which is incorporated by reference herein. STATEMENT REGARDING FEDERALLY SPONSORED R&D [0002] This invention was made with government support under Grant No. R01 GM134274 awarded by the National Institutes of Health/National Institute of General Medical Sciences. The government has certain rights in the invention. Field [0003] The present disclosure relates to polynucleotides, expression constructs, compositions, kits and methods relating to genetic disorders. Reference to Sequence Listing [0004] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled PNDRI.014WO.xml, which was created on October 6, 2023, which is 141,258 bytes in size. The information in the electronic Sequence Listing is hereby incorporated by reference in its entirety. Background [0005] OTC deficiency, the most common inherited urea cycle disorder, is caused by mutations in the X-linked gene that encodes ornithine transcarbamylase (OTC). This rare, but highly actionable disease can present with severe neonatal onset in males or with later onset in both males and females. Infants with neonatal onset appear normal at birth but rapidly develop hyperammonemia which can progress to coma, outcomes that can be prevented by rapid diagnosis and administration of ammonia scavengers. [0006] OTC was recently added to the American College of Medical Genetics list of genes for which secondary findings should be reported (PMID: 34012068). Existing biochemical assays for OTC deficiency have limitations, including the sensitivity and specificity of the citrulline assays used in newborn screening panels and the limited utility of enzymatic assays from liver biopsies in females. [0007] DNA sequencing-based diagnostics have the potential to reduce the morbidity and mortality associated with delayed treatment or underdiagnosis. However, because approximately 20-30% of OTC deficiencies occur de novo, and because only a minority of OTC variants are recurrent, DNA sequencing often returns novel sequence variants of uncertain significance (VUS). SUMMARY OF THE INVENTION [0008] This application is related to protein variants of OTC that harbor different amino acid substitutions. Any features, structures, or steps disclosed herein can be replaced with or combined with any other features, structures, or steps disclosed herein, or omitted. Further, for purposes of summarizing the disclosure, certain aspects, advantages, and features of the inventions have been described herein. It is to be understood that not necessarily any or all such advantages are achieved in accordance with any particular embodiment of the inventions disclosed herein. No individual aspects of this disclosure are essential or indispensable. [0009] In some embodiments, a protein having the amino acid sequence of any one of the SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. [0010] In some embodiments, a protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the protein with at least one of the point mutations exhibits higher activity when compared to the WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations is enhanced by at least 5% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations is enhanced by at least 10% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the point mutants comprising at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 is provided. [0011] In some embodiments, a protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C exhibits higher activity when compared to the WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 50% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the point mutants comprising at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 53, 120, 124, 143, 211, 266, 324, 325, 326, 350. [0012] In some embodiments, an expression vector which comprises a polynucleotide sequence of any one of the embodiments of the present application is provided. In some embodiments, an expression vector comprising a polynucleotide sequence encoding for one or more of the proteins of SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. In some embodiments, an expression vector comprises a codon-optimized sequence. [0013] In some embodiments, an expression vector comprising a polynucleotide sequence encoding for one or more of the proteins of any of the embodiments comprising one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the function of the protein with at least one of the point mutations is enhanced by at least 5% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of wild-type protein of SEQ ID NO:1. [0014] In some embodiments, a composition comprising the protein of any one of the SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. In some embodiments, the protein is ornithine transcarbamylase (OTC). [0015] In some embodiments, the composition is for use in the treatment of a genetic disorder. In some embodiments, the composition is administered to a subject having a genetic disorder in an amount effective to correct the genetic disorder or a symptom thereof in the subject. In some embodiments, the genetic disorder is OTC deficiency. [0016] In some embodiments, a method of enhancing the functionality of Ornithine transcarbamylase (OTC) protein in a subject is provided. The method comprises administering to the subject the protein or composition, wherein the OTC deficiency or a symptom thereof is reduced after administration. [0017] In some embodiments, the subject is a fetus, neonate, juvenile or adult. [0018] In some embodiments, a method of administering one or more expression vectors to a subject in an amount to correct the OTC deficiency or a symptom thereof in the subject is provided. [0019] In some embodiments, the OTC is modified to exhibit an enhanced function. [0020] In some embodiments, the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 to exhibit an enhanced function. [0021] In some embodiments, the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110. [0022] In some embodiments, the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 5% when compared to the function of WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations is enhanced by at least 50% when compared to the function of WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of WT protein of SEQ ID NO:1. [0023] In some embodiments, a method of screening for a protein variant is provided. In some embodiments, the method comprises providing a population of yeast strains each expressing the protein, growing the yeast strains on a minimal growth medium, screening the population of yeast strains expressing the protein variant for growth based on a growth score, identifying the protein variant based on the growth score that was screened for, and identifying a specific region or a position with an amino acid substitution of the protein variant that was identified based on the growth score, wherein the growth score of the protein variant is higher than the growth score of the WT protein. In some embodiments, the position with an amino acid substitution is further substituted with another amino acid. [0024] In some embodiments, a method of screening for a protein variant is provided. In some embodiments, the method comprises providing a population of yeast strains each expressing the protein, growing the yeast strains on a minimal growth medium, screening the population of yeast strains expressing the protein variant for growth based on a growth score, identifying the protein variant based on the growth score that was screened for, and functionally classifying the identified protein variants based on the growth score. In some embodiments, the growth score of the protein variant is higher than the growth score of the WT protein. In some embodiments, the growth score of the protein variant is lower than the growth score of the WT protein. In some embodiments, the growth score of the protein variant is same as the growth score of the WT protein. [0025] In some embodiments, a kit for determining a specific mode of treatment of a genetic disorder is provided. The kit comprises a look up table. The look up table indicates specific amino acid substitutions that are commonly involved in a cellular mechanism; and one or more vectors comprising sequences of SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. [0026] In some embodiments, the look up table comprising a list of mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. [0027] In some embodiments, the genetic disorder is OTC deficiency. [0028] In some embodiments, a method of identifying a subject having a genetic disorder is provided. The method comprises detecting a presence of at least one mutation in the protein that is different in the subject with the genetic disorder as compared to a subject without the disorder, wherein the presence of at least one mutation indicates the presence of the genetic disorder in the subject. [0029] In some embodiments, a method of improving, ameliorating, or treating a genetic disorder is provided. The method comprises detecting a presence of at least one mutation in the protein that is different in the subject with the genetic disorder as compared to a subject without the disorder, wherein the presence of at least one mutation indicates the presence of the genetic disorder in the subject. The method also comprises administering to the subject at least one protein variant or composition provided herein in the embodiments, wherein the genetic disorder or a symptom thereof is reduced after administration. [0030] In some embodiments, the mutation to be detected is selected from a group consisting of: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. [0031] In some embodiments, one mutation that indicates the presence of genetic disorder in the subject is selected from the mutations in Table 3. [0032] In some embodiments, an engineered protein administered to the subject including one or more of the mutations in Table 2 is provided. [0033] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1, selected from the group consisting of any one of the mutations: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. [0034] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. [0035] In some embodiments, a composition comprising a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1, selected from the group consisting of any one of the mutations: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the protein is ornithine transcarbamylase (OTC). [0036] In some embodiments, a method for identifying a subject having a genetic disorder is provided. In some embodiments, the method comprises detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder that exhibits dominant negative interactions with a wildtype protein of SEQ ID NO:1, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject. [0037] In some embodiments, a method of improving, ameliorating, or treating a genetic disorder is provided. In some embodiments, the method comprises detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder that exhibits dominant negative interactions with a wildtype protein of SEQ ID NO:1, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject and administering to the subject the protein or composition disclosed herein, wherein the genetic disorder or a symptom thereof is reduced after administration. In some embodiments, the subject is a fetus, neonate, juvenile or adult. In some embodiments, the mutation is selected from R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L. [0038] In some embodiments, a kit for identifying proteins with specific amino acid substitutions is provided. In some embodiments, the kit comprises a look up table, wherein the look up table indicates proteins with specific amino acid substitutions that exhibit dominant negative interactions with a wildtype protein of SEQ ID NO:1. In some embodiments, the look up table comprising a list of mutations as follows: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L is provided. [0039] In some embodiments, a method of screening for a protein variant that exhibits dominant negative interactions with a wildtype protein is provided. In some embodiments, the method comprises providing a population of haploid yeast strains each expressing a protein variant disclosed herein, mixing the population of haploid yeast strains expressing the protein variant with a haploid yeast strain expressing a WT protein to generate a population of diploid yeast strains each expressing a variant protein in combination with the WT protein, growing the diploid yeast strains on a minimal growth medium, screening the population of diploid yeast strains expressing a variant protein in combination with the WT protein for growth based on a growth score and identifying a protein variant that exhibits dominant negative interactions with a wildtype protein based on the growth score that was screened for. In some embodiments, the minimal growth medium lacks arginine. BRIEF DESCRIPTION OF THE DRAWINGS [0040] The foregoing and other features of the present disclosure will become more fully apparent from the following description, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only some embodiments in accordance with the disclosure and are therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings. [0041] Figure 1 illustrates the sequence of human OTC protein. [0042] Figure 2 illustrates the sequence of the human OTC protein where amino acid positions that can be substituted in the sequence are depicted with X. [0043] Figures 3 illustrates the sequence of human OTC protein variant of SEQ ID NOs: 3-20. [0044] Figures 4 illustrates the sequence of human OTC protein variant of SEQ ID NO: 21-40. [0045] Figures 5 illustrates the sequence of human OTC protein variant of SEQ ID NO: 41-60. [0046] Figures 6 illustrates the sequence of human OTC protein variant of SEQ ID NO: 61-80. [0047] Figures 7 illustrates the sequence of human OTC protein variant of SEQ ID NO: 81-100. [0048] Figures 8 illustrates the sequence of human OTC protein variant of SEQ ID NO: 101-110. [0049] Figure 9 illustrates the sequence of the expression construct set forth in GenBank accession No: ON872185 [0050] Figure 10 shows the results of a quantitative yeast assay for OTC function in the absence of arginine. Growth in the absence of exogenously supplied arginine, for wildtype strain (codon optimized human OTC gene) and strains with amino acid substitute mutations in human OTC. The growth values (y-axis) plotted as points on a scatter plot ordered by their amino acid position (x-axis). [0051] Figure 11 shows the results of a quantitative yeast assay of OTC variants in the absence of arginine. Growth in the absence of arginine for yeast haploid OTC variants and heterozygous diploid yeast strains (yOTC variant/wild type yOTC). The growth values (y- axis) are plotted for the respective yeast haploid OTC variants and heterozygous diploid yeast strains (yOTC variant/wild type yOTC) (x-axis). Growth values are expressed relative to the relevant (haploid or heterozygous diploid) wildtype yOTC control with a value of 1.0. DETAILED DESCRIPTION [0052] The currently existing biochemical assays for detecting OTC deficiency are citrulline assays used in the newborn screening panels and enzymatic assays from liver biopsies in females. These assays have limitations, including the sensitivity and specificity of the citrulline assays used in newborn screening panels and the limited utility of enzymatic assays from liver biopsies in females. In addition, only a minority of OTC variants are recurrent and DNA sequencing-based diagnostics often returns novel sequence variants of uncertain significance (VUS). [0053] Identification of protein variants with specific attributes can be used to stratify patients for specific therapeutics. Because it is not currently possible to computationally predict the functional consequences of all amino acid substitution mutations, results from functional assays, such as those described here for OTC, are needed to accurately and quantitatively determine the degree to which an amino acid substitution will (or will not) alter a protein’s activity, stability, or both. [0054] In addition, there is also limited data about the extent to which the activity of wildtype OTC introduced by enzyme replacement therapy might be negatively influenced by the different OTC variants encoded by a patient’s genome. Such dominant negative interactions occur when expression of a protein variant disrupts the function of the wildtype protein resulting in combined activity that is lower than that expected given the activity of each variant individually. The information from the results of functional assays, such as those described here for OTC, are needed to understand the extent to which dominant negative interactions are likely to occur and enable the prioritization of potentially problematic alleles for further study in mammalian cell or animal models. [0055] Provided herein are protein variants of OTC. In some embodiments, they can be used for application in which protein variants with increased activity and/or stability are desired. Also disclosed herein are protein variants with reduced activity and/or stability that can be used to diagnose OTC deficiency. Also disclosed herein are protein variants that exhibit dominant negative interactions with a wildtype OTC protein. In some embodiments, the expression of a protein variant disrupts the function of the wildtype OTC protein resulting in combined activity that is lower than that expected given the activity of each variant individually. In some embodiments, protein variants with increased activity and/or stability can be used to replace or supplement the protein variants with reduced activity,stability and/or the protein variants that exhibit dominant negative interactions with a wildtype OTC protein —in some embodiments, this identification can then be used to then treat the subject as provided herein (e.g., via an increase in activity and/or function of OTC). [0056] In some embodiments, a method of improving, ameliorating, or treating a genetic disorder is provided. The method comprises detecting the presence of at least one mutation that results in the protein variant with reduced activity and/or stability that is different in the subject with genetic disorder as compared to a subject without the disorder , wherein the presence of at least one mutation that results in the protein variant with reduced activity and/or stability indicates the presence of genetic disorder in the subject. In some embodiments, the method comprises detecting the presence of at least one protein coding variant that exhibits dominant negative interactions with a wildtype protein and is different in the subject with the genetic disorder as compared to a subject without the disorder. The method further comprises administering a composition comprising at least one protein variant with increased activity and/or stability to the subject, wherein the genetic disorder or a symptom thereof is reduced after administration. Terminology [0057] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. [0058] As used herein, “a” or “an” may mean one or more than one. [0059] “About” as used herein when referring to a measurable value is meant to encompass variations of ±20% or ±10%, more preferably ±5%, even more preferably ±1%, and still more preferably ±0.1 % from the specified value. [0060] Conditional language, such as “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements, and/or steps. Thus, such conditional language is not generally intended to imply that features, elements, and/or steps are in any way required for one or more embodiments. [0061] The terms “comprising,” “including,” “having,” and the like are synonymous and are used inclusively, in an open-ended fashion, and do not exclude additional elements, features, acts, operations, and so forth. Also, the term “or” is used in its inclusive sense (and not in its exclusive sense) so that when used, for example, to connect a list of elements, the term “or” means one, some, or all of the elements in the list. [0062] The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. [0063] Numbers preceded by a term such as “approximately”, “about”, and “substantially” as used herein include the recited numbers (e.g., about 10% = 10%), and also represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, and “substantially” may refer to an amount that is within less than 10% of, within less than 5% of, within less than 1% of, within less than 0.1% of, and within less than 0.01% of the stated amount. [0064] “Polynucleotide,” as described herein refers to “nucleic acid” or “nucleic acid molecule,” such as deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), oligonucleotides, fragments generated by the polymerase chain reaction (PCR), and fragments generated by any of ligation, scission, endonuclease action, and exonuclease action. Nucleic acid molecules can be composed of monomers that are naturally- occurring nucleotides (such as DNA and RNA), or analogs of naturally- occurring nucleotides (e.g, enantiomeric forms of naturally- occurring nucleotides), or a combination of both. Modified nucleotides can have alterations in sugar moieties and/or in pyrimidine or purine base moieties. Sugar modifications include, for example, replacement of one or more hydroxyl groups with halogens, alkyl groups, amines, and azido groups, or sugars can be functionalized as ethers or esters. Moreover, the entire sugar moiety can be replaced with sterically and electronically similar structures, such as aza-sugars and carbocyclic sugar analogs. Examples of modifications in a base moiety include alkylated purines and pyrimidines, acylated purines or pyrimidines, or other well- known heterocyclic substitutes. Nucleic acid monomers can be linked by phosphodiester bonds or analogs of such linkages. Analogs of phosphodiester linkages include phosphorothioate, phosphorodithioate, phosphoroselenoate, phosphorodiselenoate, phosphoroanilothioate, phosphoranilidate, phosphoramidate, and the like. The term “nucleic acid molecule” also includes so-called “peptide nucleic acids,” which comprise naturally occurring or modified nucleic acid bases attached to a polyamide backbone. Nucleic acids can be either single stranded or double stranded. In some alternatives, a nucleic acid sequence encoding a fusion protein is provided. In some alternatives, the nucleic acid is RNA or DNA. [0065] The terms “peptide”, “polypeptide”, and “protein” as used herein have their plain and ordinary meaning as understood in light of the specification and refer to macromolecules comprised of amino acids linked by peptide bonds. The numerous functions of peptides, polypeptides, and proteins are known in the art, and include but are not limited to enzymes, structure, transport, defense, hormones, or signaling. Peptides, polypeptides, and proteins are often, but not always, produced biologically by a ribosomal complex using a nucleic acid template, although chemical syntheses are also available. By manipulating the nucleic acid template, peptide, polypeptide, and protein mutations such as substitutions, deletions, truncations, additions, duplications, or fusions of more than one peptide, polypeptide, or protein can be performed. These fusions of more than one peptide, polypeptide, or protein can be joined in the same molecule adjacently, or with extra amino acids in between, e.g. linkers, repeats, epitopes, or tags, or any other sequence that is, is about, is at least, is at least about, is not more than, or is not more than about, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, or 300 residues long, or any length in a range defined by any two of the aforementioned lengths. [0066] “Hyperactive variant” as described herein refers to a protein with at least one amino acid substitution that has increased activity as compared to wild type or native protein. Hyperactive variant exhibits an enhanced functionality, abundance, activity, specificity, affinity or a combination of the aforementioned parameters as compared to wild type or native protein. [0067] The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, gamma-carboxyglutamate, and O-phosphoserine. Amino acid analogs refer to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an .alpha.- carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid. [0068] The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, gamma-carboxyglutamate, and O-phosphoserine. Amino acid analogs refer to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an .alpha.- carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid. [0069] “Expression construct” or “construct” or “an expression vector” or a “vector” as described herein, is a nucleic acid used to introduce heterologous nucleic acids into a cell that has regulatory elements to provide expression of the heterologous nucleic acids in the cell. Typically, an expression vector comprises a transcriptional promoter, a gene, and a transcription terminator. Gene expression is usually placed under the control of a promoter, and such a gene is said to be “operably linked to” the promoter. Similarly, a regulatory element and a core promoter are operably linked if the regulatory element modulates the activity of the core promoter. The constructs described herein include but are not limited to plasmid, minicircles, yeast, and viral genomes. [0070] A single copy of the construct is inserted stably into the yeast genome (at either the same position as the yeast gene, which has been deleted or at a neutral position in the genome, e.g. the HO locus). In the embodiments herein, the construct is a “linear DNA molecule (double or single stranded) that can be integrated into the yeast nuclear or mitochondrial genome by homologous recombination. These constructs may be synthesized in vitro by a commercial gene synthesis company (e.g. Twist Biosciences or IDT). As such the nucleic acid sequence could be the human sequence or a yeast optimized version that encodes the same protein sequence. [0071] “Coding for" or “encoding” have their plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, the property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other macromolecules such as a defined sequence of amino acids. Thus, a gene codes for a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. [0072] The terms “identical” or percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, refer to two or more sequences or subsequences that are the same sequences. Two sequences are “substantially identical” if two sequences have a specified percentage of amino acid residues or nucleotides that are the same (for example, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity over a specified region, or, when not specified, over the entire sequence of a reference sequence), when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Some embodiments provided herein provide polypeptides or polynucleotides that are substantially identical to the polypeptides or polynucleotides, respectively, exemplified herein. Optionally, the identity exists over a region that is at least about 15, 25 or 50 nucleotides in length, or more preferably over a region that is 100 to 500 or 1000 or more nucleotides in length, or over the full length of the reference sequence. With respect to amino acid sequences, identity or substantial identity can exist over a region that is at least 5, 10, 15 or 20 amino acids in length, optionally at least about 25, 30, 35, 40, 50, 75 or 100 amino acids in length, optionally at least about 150, 200 or 250 amino acids in length, or over the full length of the reference sequence. With respect to shorter amino acid sequences, e.g., amino acid sequences of 20 or fewer amino acids, in some embodiments, substantial identity exists when one or two amino acid residues are conservatively substituted, according to the conservative substitutions defined herein. [0073] Moreover, while illustrative embodiments have been described herein, the scope of any and all embodiments having equivalent elements, modifications, omissions, combinations (e.g., of aspects across various embodiments), adaptations and/or alterations as would be appreciated by those in the art based on the present disclosure. The limitations in the claims are to be interpreted broadly based on the language employed in the claims and not limited to the examples described in the present specification or during the prosecution of the application, which examples are to be construed as non-exclusive. Further, the actions of the disclosed processes and methods may be modified in any manner, including by reordering actions and/or inserting additional actions and/or deleting actions. It is intended, therefore, that the specification and examples be considered as illustrative only, with a true scope and spirit being indicated by the claims and their full scope of equivalents. [0074] The terms “individual”, “subject”, “host,” or “patient” as used herein have their usual meaning as understood by those skilled in the art and thus includes a human or a non-human mammal. The term “mammal” is used in its usual biological sense. Thus, it specifically includes, but is not limited to, primates, including simians (chimpanzees, apes, monkeys), humans, cattle, horses, sheep, goats, swine, rabbits, dogs, cats, rodents, rats, mice, or guinea pigs. The subject as described in the embodiments herein may be a fetus, neonate, juvenile or adult. “Fetus” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a prenatal human between its embryonic state and its birth. “Neonate” refers to a newborn child. “Juvenile” refers to a person under the established age of 18 years. “Adult” refers to a person any age over 18. [0075] “Look-up table” has its plain and ordinary meaning when read in light of the specification, and may include but is not limited to, for example, a table prepared with a list or combination of protein variants that may exhibit increased or decreased levels of activity and/or stability. The data on the look-up table also provide different predicted thresholds for determining the functions of different point mutations as there are different thresholds for combinations of alleles for different diseases. [0076] “Cell growth” also referred to as the “growth value”, is an experimentally measured amount of the extent to which yeast cells are able to grow under specific environmental conditions. In some embodiments, cell growth, also the “growth value”, is measured by optical density of a liquid culture. In some embodiments, cell growth, also the “growth value”, is measured by the area of a “patch” or “spot” of cells growing on solid media, the number of pixels of a “patch” or “spot” of cells growing on solid media, the intensity of the pixels in a “patch” or “spot” of cells growing on solid media, the change in any of these parameters over time, or a combination of any of the aforementioned parameters. [0077] As used herein, by “pharmaceutically acceptable” or “pharmacologically compatible” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to a subject without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers or excipients have preferably met the required standards of toxicological and manufacturing testing and/or are included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug administration. [0078] “Codon optimization” or “codon optimized” refers to changes made in the nucleotide sequence so that it is more likely to be expressed at a relatively high level and translated at a higher efficiency as compared to the non-codon optimized sequence. Codon optimization does not change the amino acid for which the codon encodes. [0079] “Codon harmonization” or “codon harmonized” refers to changes made in a nucleotide sequence that does not change the identity of the amino acid encoded by the codon. Codon harmonization preserves codon preferences of the original genes and seeks to match the codon frequency at an amino acid position between two orthologous genes. [0080] The term “dominant negative variant” is a version of a protein that interferes with the function of another protein. Another protein can be the same or different than the protein that harbors the dominant negative variant. A dominant negative variant can be a full-length protein, a protein with one or more amino acid mutations, a truncation, a deletion, or a fusion of wild type or mutant proteins. [0081] As used herein, “treatment” or “therapy” of a disease or condition refers to reducing the severity, frequency, or occurrence of at least one symptom of that disease or condition, compared to a similar but untreated patient. Treatment can also refer to reducing, halting, slowing, or reversing the progression of a disease or condition, compared to a similar but untreated patient. Treatment may further comprise addressing the root cause of the disease and/or one or more symptoms. The term “prevent” does not require the absolute prohibition of the disorder or disease. [0082] The terms “amount effective” “effective amount” or “effective dose” as used herein have their usual meaning as understood by those skilled in the art and refer to that amount of a recited composition or compound that results in an observable biological effect. Actual dosage levels of active ingredients in an active composition of the presently disclosed subject matter can be varied so as to administer an amount of the active composition or compound that is effective to achieve the desired response for a particular subject and/or application. The selected dosage level will depend upon a variety of factors including, but not limited to, the activity of the composition, formulation, route of administration, combination with other drugs or treatments, severity of the condition being treated, and the physical condition and prior medical history of the subject being treated. In some embodiments, a minimal dose is administered, and dose is escalated in the absence of dose-limiting toxicity to a minimally effective amount. Determination and adjustment of an effective dose, as well as evaluation of when and how to make such adjustments, are contemplated herein. In the case of OTC deficiency, an effective amount of protein or composition comprising a protein as disclosed herein, can increase the activity of the deficient protein involved in OTC deficiency. In some embodiments, the therapeutically effective amount of protein or composition comprising a protein as disclosed herein, can increase the stability of the deficient protein involved in OTC deficiency. In some embodiments, the therapeutically effective amount is an amount that extends the survival of a subject. In some embodiments, the therapeutically effective amount is an amount that reduces one or more symptoms associated with the OTC deficit in the subject. [0083] “Conservative substitutions” involve the replacement of an amino acid with a different amino acid having similar properties. For example, an aliphatic residue may be replaced by another aliphatic residue, a non-polar residue may be replaced by another non- polar residue, an acidic residue may be replaced by another acidic residue, a basic residue may be replaced by another basic residue, a polar residue may be replaced by another polar residue or an aromatic residue may be replaced by another aromatic residue. “Non-conservative substitutions” involve the replacement of an amino acid with a different amino acid having different properties. Amino acids may be grouped into different classes according to common side-chain properties: a. hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; b. neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; c. acidic: Asp, Glu; d. basic: His, Lys, Arg; e. residues that influence chain orientation: Gly, Pro; aromatic: Trp, Tyr, Phe. Non-conservative substitutions will entail exchanging a member of one of these classes for another class. [0084] In some embodiments, a protein having the amino acid sequence of any one of the SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. [0085] In some embodiments, a protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the protein has at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 100%, or any integer that is between 80 and 100%, identity to SEQ ID NO: 1 (wild type sequence). In some embodiments, the protein has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 100%, or any integer that is between 70 and 100%, identity to SEQ ID NO: 1. In some embodiments, the protein has at least 80% identity to SEQ ID NO:1. In some embodiments, the protein has at least 90% identity to SEQ ID NO:1. [0086] In some embodiments, the protein variants having the amino acid sequence of the SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 can differ from a wild type sequence of Figure 1 and SEQ ID NO:1 by substitution of 1 amino acid, 2, 3, 4, 5-10, 10-20 or 20-30 or 30-40, 40-50, 50-60, 60-70 or 70-80 amino acids. In some embodiments, a variant sequence can comprise the wild type sequence of Figure 1 and SEQ ID NO:1 with 1 residue, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more residues substituted. For example, 5, 10, 15, up to 20, up to 30 or up to 40, up to 50, up to 60, up to 70, up to 80 residues can be substituted (using the substitutions specified herein, especially those that increase activity of OTC). In some embodiments, a variant sequence can have 1 residue, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30 or more residues substituted with a conservative amino acid. In other embodiments, a variant sequence can have 1 residue, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30 or more residues substituted with a non-conservative amino acid. In some embodiments, any one or more of the mutations listed in any one of Table 1 and/or 2 can be combined, including 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90100 or more of the point mutations listed in these tables. [0087] In some embodiments, the mutants provided herein are mutants that confer increased activity and/or stability to the protein. In some embodiments, the mutants provided herein can confer an enhanced function, stability, or activity to the protein. In some embodiments, the mutants provided herein are rescue mutants. In some embodiments, the mutants provided herein can rescue the altered function, stability, or activity of the protein. In other embodiments, the mutations result in the opposite. [0088] In some embodiments, the mutants specified herein can be used to enhance or rescue the function, stability or activity of the protein if the ratio ofactivity of the protein variant to wildtype is 1, 1.05, 1.1, 1.15, 1.2, 1.25 or higher (e.g., from any of the noted tables). [0089] In some embodiments, the mutants specified herein can be used to enhance or rescue the function, stability or activity of the protein if the ratio of activity of the protein variant to wild-type protein is higher than 0.95. [0090] In some embodiments, the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C exhibits higher activity when compared to the WT protein of SEQ ID NO:1. In some embodiments, the activity of the protein can comprise but is not limited to enzymatic activity, expression levels, catalytic activity, and/or binding activity. In some embodiments, at least one or more of the point mutations results in a change in activity of the protein as compared to the wild-type protein. In some embodiments, the activity is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%,200%, 300%, 400% or greater or any integer that is between 1 and 400%, more than the activity of the wild-type protein. In some embodiments, the ratio of activity of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of activity of the protein variant to wild-type protein is at least 1, 1.05, 1.1, 1.15, 1.2, 1.25 or higher. [0091] In some embodiments, the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 5% when compared to the function of wild-type protein of SEQ ID NO:1. [0092] In some embodiments, the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10, 20, 30, 40, 50, 100% or more when compared to the function of wild-type protein of SEQ ID NO:1. [0093] In some embodiments, the functionality is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100,%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, more than the functionality of the wild-type protein. In some embodiments, the ratio of functionality between the wild-type protein and the protein variant is 1 or more than 1. In some embodiments, the ratio of functionality of the protein variant to wild-type protein is 1, 1.01, 1.02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2 or higher as listed in Tables 1 and/or 2. [0094] In some embodiments, at least one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C results in a change in expression of the protein as compared to the wild-type protein. In some embodiments, the functionality is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any integer that is between 1 and 400%, more than the expression of the wild-type protein. In some embodiments, the ratio of expression of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of expression of the protein variant to wild-type protein is 1, 1.05, 1.1, 1.15, 1.2, 1.25 or higher. [0095] In some embodiments, at least one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C results in a change in abundance of the protein as compared to the wild-type protein. In some embodiments, the abundance is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any integer that is between 1 and 400%, more than the abundance of the wild-type protein. In some embodiments, the ratio of abundance of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of abundance of the protein variant to wild-type protein is 1, 1.05, 1.1, 1.15, 1.2, 1.25 or higher. [0096] In some embodiments, at least one or more of the point mutations results in a change in specificity of the protein as compared to the wild-type protein. In some embodiments, the specificity is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any integer that is between 1 and 400%, more than the specificity of the wild-type protein. In some embodiments, the ratio of specificity of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of specificity of the protein variant to wild-type protein is 1, 1.05, 1.1, 1.15, 1.2, 1.25 or higher. [0097] In some embodiments, at least one or more of the point mutations results in a change in affinity of the protein as compared to the wild-type protein. In some embodiments, the abundance is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any integer that is between 1 and 400%, more than the affinity of the wild-type protein. In some embodiments, the ratio of affinity between the wild-type protein and the protein variant is 1 or more than 1. In some embodiments, the ratio of affinity of the protein variant to wild-type protein is 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 2, 2.5, 3, 3.5, or 4 or more. [0098] In some embodiments, point mutations result in a change in functionality, abundance, activity, specificity, affinity or a combination of the aforementioned parameters. [0099] In some embodiments, the point mutants comprising at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 is provided. [0100] In some embodiments, the amino acid at least one position denoted by X in Figure 2 can be substituted. In some embodiments, the amino acid in 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more positions denoted by X can be substituted. For example, the amino acid in 5, 10, 15, up to 20, up to 30 or up to 40, up to 50, up to 60, up to 70, up to 80 positions denoted by X can be substituted. In some embodiments, the amino acid at the positions denoted by X in Figure 2, 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 can be substituted by a conservative substitution. In some embodiments, the amino acid at the positions denoted by X in Figure 2, 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 can be substituted by a non- conservative substitution. In some embodiments, the amino acid at the positions denoted by X in Figure 2, 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 can be substituted by a combination of conservative and non- conservative substitutions. [0101] In some embodiments, a protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the protein has at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 100%, or any integer that is between 80 and 100%, identity to SEQ ID NO: 1 (wild type sequence). In some embodiments, the protein has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 100%, or any integer that is between 70 and 100%, identity to SEQ ID NO: 1. In some embodiments, the protein has at least 80% identity to SEQ ID NO:1. In some embodiments, the protein has at least 90% identity to SEQ ID NO:1. [0102] In some embodiments, a protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the protein has at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 100%, or any integer that is between 80 and 100%, identity to SEQ ID NO: 1 (wild type sequence). In some embodiments, the protein has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 100%, or any integer that is between 70 and 100%, identity to SEQ ID NO: 1. In some embodiments, the protein has at least 80% identity to SEQ ID NO:1. In some embodiments, the protein has at least 90% identity to SEQ ID NO:1. [0103] In some embodiments, the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C exhibits higher activity when compared to the WT protein of SEQ ID NO:1. In some embodiments, the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C exhibits higher activity when compared to the WT protein of SEQ ID NO:1. In some embodiments, the activity of the protein can comprise but is not limited to enzymatic activity, expression levels, catalytic activity, and/or binding activity. In some embodiments, at least one or more of the point mutations results in a change in activity of the protein as compared to the wild-type protein. In some embodiments, the activity is at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%,200%, 300%, 400% or greater or any integer that is between 1 and 400%, more than the activity of the wild-type protein. In some embodiments, the ratio of activity of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of activity of the protein variant to wild- type protein is at least 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.4, 1.5 or higher. In some embodiments, the ratio of activity of the protein variant to wild-type protein is 1.2. In some embodiments, the ratio of activity of the protein variant to wild-type protein is 1.25. [0104] In some embodiments, the mutants specified herein can be used to enhance or rescue the function, stability or activity of the protein if the ratio of activity of the protein variant to wild-type protein is higher than 1.1. In some embodiments, the mutants specified herein can be used to enhance or rescue the function, stability or activity of the protein if the ratio of activity of the protein variant to wild-type protein is higher than 1.2. In some embodiments, the mutants specified herein can be used to enhance or rescue the function, stability or activity of the protein if the ratio of activity of the protein variant to wild-type protein is higher than 1.25. In some embodiments, the mutants specified herein can be used to enhance or rescue the function, stability or activity of the protein if the ratio of activity of the protein variant to wild-type protein is higher than 1.3. In some embodiments, the mutants specified herein can be used to enhance or rescue the function, stability or activity of the protein if the ratio of activity of the protein variant to wild-type protein is higher than 1.4. [0105] In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10% when compared to the function of wild-type protein of SEQ ID NO:1. [0106] In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 50% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 50% when compared to the function of wild-type protein of SEQ ID NO:1. [0107] In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10, 20, 30, 40, 50, 100% or more when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10, 20, 30, 40, 50, 100% or more when compared to the function of wild-type protein of SEQ ID NO:1. [0108] In some embodiments, the functionality is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100,%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, more than the functionality of the wild-type protein. In some embodiments, the ratio of functionality of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of functionality of the protein variant to wild-type protein is 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2, 1.3, 1.4 or higher as listed in Tables 1 and/or 2. [0109] In some embodiments, at least one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C results in a change in expression of the protein as compared to the wild-type protein. In some embodiments, at least one or more of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C results in a change in expression of the protein as compared to the wild-type protein. In some embodiments, the functionality is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any integer that is between 1 and 400%, more than the expression of the wild-type protein. In some embodiments, the ratio of expression of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of expression of the protein variant to wild-type protein is 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.4 or higher. [0110] In some embodiments, at least one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C results in a change in abundance of the protein as compared to the wild-type protein. In some embodiments, at least one or more of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C results in a change in abundance of the protein as compared to the wild-type protein. In some embodiments, the abundance is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any integer that is between 1 and 400%, more than the abundance of the wild-type protein. In some embodiments, the ratio of abundance of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of abundance of the protein variant to wild-type protein is 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.4 or higher. [0111] In some embodiments, at least one or more of the point mutations results in a change in specificity of the protein as compared to the wild-type protein. In some embodiments, the specificity is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any integer that is between 1 and 400%, more than the specificity of the wild-type protein. In some embodiments, the ratio of specificity of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of specificity of the protein variant to wild-type protein is 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.4 or higher. [0112] In some embodiments, at least one or more of the point mutations results in a change in affinity of the protein as compared to the wild-type protein. In some embodiments, the abundance is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any integer that is between 1 and 400%, more than the affinity of the wild-type protein. In some embodiments, the ratio of affinity of the protein variant to wild- type protein is 1 or more than 1. In some embodiments, the ratio of affinity of the protein variant to wild-type protein is 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 2, 2.5, 3, 3.5, or 4 or more. [0113] In some embodiments, point mutations result in a change in functionality, abundance, activity, specificity, affinity or a combination of the aforementioned parameters. [0114] In some embodiments, the point mutants comprising at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 is provided. In some embodiments, the amino acid in at least one of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in at least two of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in at least three of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in at least four of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in at least five of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in at least six of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in at least seven of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in at least eight of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in at least nine of the positions of SEQ ID NO:1, 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted. In some embodiments, the amino acid in 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 positions of SEQ ID NO:1 can be substituted. [0115] In some embodiments, the point mutants comprising at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 is provided. In some embodiments, the amino acid in at least one of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in at least two of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in at least three of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in at least four of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in at least five of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in at least six of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in at least seven of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in at least eight of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in at least nine of the positions of SEQ ID NO:1, 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted. In some embodiments, the amino acid in 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 positions of SEQ ID NO:1 can be substituted. [0116] In some embodiments, the amino acid at the positions of SEQ ID NO:1, selected from the group consisting of 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted by a conservative substitution. In some embodiments, the amino acid at the positions of SEQ ID NO:1, selected from the group consisting of 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted by a non- conservative substitution. In some embodiments, the amino acid at the positions of SEQ ID NO:1, selected from the group consisting of 53, 120, 124, 143, 211, 266, 324, 325, 326, 350 can be substituted by a combination of conservative and non- conservative substitutions. [0117] In some embodiments, the amino acid at the positions of SEQ ID NO:1, selected from the group consisting of 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted by a conservative substitution. In some embodiments, the amino acid at the positions of SEQ ID NO:1, selected from the group consisting of 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted by a non- conservative substitution. In some embodiments, the amino acid at the positions of SEQ ID NO:1, selected from the group consisting of 53, 56, 101, 114, 120, 124, 134, 143, 163, 211, 217, 255, 257, 264, 266, 267, 285, 286, 307, 324, 325, 326, 333, 340, 350 can be substituted by a combination of conservative and non- conservative substitutions. [0118] In some embodiments, an expression vector which comprises a polynucleotide sequence of any one of the embodiments of the present application is provided. In some embodiments, the polynucleotide sequence is a human sequence. In other embodiments, the polynucleotide sequence is a yeast optimized version that encodes the human sequence. [0119] In some embodiments, an expression vector comprising a polynucleotide sequence encoding for one or more of the proteins of SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. [0120] In some embodiments, an expression vector comprises a codon-optimized sequence. In other embodiments, the expression vector comprises a sequence that is not codon- optimized. [0121] In some embodiments, the expression vector as set forth in GenBank accession No. ON872185, and as depicted in SEQ ID NO: 111 and Figure 9 including 1-6055= Cloning vector AB614_yOTC, 1-1335= pUC19 sequence, 1344-1652= HO-L recombination- directing sequence derived from Saccharomyces cerevisiae, 1656-2066= ARG3 promoter from S. cerevisiae, 2067-3038= Homo sapiens ornithine transcarbamylase codon, optimized for expression in S. cerevisiae, 3039-3429= TRP2 terminator from S. cerevisiae, 3440-3818= TEF promoter from A. gossypii, 3819-4391= confers clonNAT resistance, 4397-4594= TEF terminator from A. gossypii, 4595-4679= Vector sequence from plasmid pFA6a-natMX6, 4680-4715= HO-R recombination-directing sequence derived from S. cerevisiae and 4722- 6055= pUC19 sequence can be used. In some embodiments, base pairs 1656-4679 of the expression vector can be inserted into the yeast genome to allow the expression of wild-type ornithine transcarbamylase or a mutant ornithine transcarbamylase. In some embodiments, 1656-2066= ARG3 promoter from S. cerevisiae, 3039-3429= TRP2 terminator from S. cerevisiae, 3440-3818= TEF promoter from A. gossypii, 3819-4391= confers clonNAT resistance, 4397-4594= TEF terminator from A. gossypii, 4595-4679= Vector sequence from plasmid pFA6a-natMX6 are needed to direct the integration and drive expression of the ornithine transcarbamylase in the yeast genome. In some embodiments, 1656-2066= ARG3 promoter from S. cerevisiae, 3039-3429= TRP2 terminator from S. cerevisiae, 3440-3818= TEF promoter from A. gossypii, 3819-4391= confers clonNAT resistance, 4397-4594= TEF terminator from A. gossypii, 4595-4679= Vector sequence from plasmid pFA6a-natMX6 are not needed to direct the integration and drive expression of the ornithine transcarbamylase in the human genome. In some embodiments, an expression vector comprising base pairs 2067- 3038 that correspond to the coding sequence of human ornithine transcarbamylase, can be used for genetic editing in human genome. In some embodiments, any expression vector that can introduce a gene according to embodiments provided herein into the yeast or human genome can be used. [0122] In some embodiments, an expression vector comprising a polynucleotide sequence encoding for one or more of the proteins of any of the embodiments comprising one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. The function of the protein variants encoded by the expression vector is enhanced by at least 5% when compared to the function of wild-type protein of SEQ ID NO:1. [0123] In some embodiments, the functionality is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100,%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, more than the functionality of the wild-type protein. In some embodiments, the ratio of functionality of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of functionality of the protein variant to wild-type protein is 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2 or higher as listed in Tables 1 and/or 2. [0124] In some embodiments, an expression vector comprising a polynucleotide sequence encoding for one or more of the proteins of any of the embodiments comprising one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the functionality is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100,%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, more than the functionality of the wild-type protein. In some embodiments, the ratio of functionality of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of functionality of the protein variant to wild- type protein is 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2, 1.3, 1.4 or higher as listed in Tables 1 and/or 2. [0125] In some embodiments, an expression vector comprising a polynucleotide sequence encoding for one or more of the proteins of any of the embodiments comprising one or more of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of wild-type protein of SEQ ID NO:1. In some embodiments, the functionality is at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100,%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, more than the functionality of the wild-type protein. In some embodiments, the ratio of functionality of the protein variant to wild-type protein is 1 or more than 1. In some embodiments, the ratio of functionality of the protein variant to wild-type protein is 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2, 1.3, 1.4 or higher as listed in Tables 1 and/or 2. [0126] In some embodiments, a composition comprising the protein of any one of the SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. [0127] In some embodiments, a composition comprising an expression vector comprising a polynucleotide sequence encoding for one or more of the proteins of SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. [0128] In some embodiments, a composition is provided comprising a protein described above and a pharmaceutically acceptable carrier. In some embodiments, a composition is provided comprising an expression vector encoding a protein according to any of the embodiments described above and a pharmaceutically acceptable carrier. [0129] In some embodiments, the protein is Ornithine Transcarbamylase (OTC). [0130] In some embodiments, the composition is for use in the treatment of a genetic disorder. [0131] In some embodiments, the composition comprising a protein variant comprising one or more point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the ratio of functionality of the protein variant used in the treatment of a genetic disorder exhibit to wild-type protein is 1 or more than 1. For example, a protein variant with a functionality ratio of 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2 or higher as listed in Tables 1 and/or 2 can be used in the treatment of a genetic disorder. In some embodiments, two or more protein variants with the same functionality ratios can be used in the treatment of the genetic disorder. In other embodiments, two or more protein variants with different functionality ratios can be used in the treatment of the genetic disorder. [0132] In some embodiments, the composition comprising a protein variant comprising one or more point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the ratio of functionality between the wild-type protein and the protein variant used in the treatment of a genetic disorder exhibit is 1 or more than 1. For example, a protein variant with a functionality ratio of 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2, 1.3, 1.4 or higher as listed in Tables 1 and/or 2 can be used in the treatment of a genetic disorder. In some embodiments, two or more protein variants with the same functionality ratios can be used in the treatment of the genetic disorder. In other embodiments, two or more protein variants with different functionality ratios can be used in the treatment of the genetic disorder. [0133] In some embodiments, the composition comprising a protein variant comprising one or more point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the ratio of functionality of the protein variant used in the treatment of a genetic disorder exhibit to wild-type protein is 1 or more than 1. For example, a protein variant with a functionality ratio of 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2, 1.3, 1.4 or higher as listed in Tables 1 and/or 2 can be used in the treatment of a genetic disorder. In some embodiments, two or more protein variants with the same functionality ratios can be used in the treatment of the genetic disorder. In other embodiments, two or more protein variants with different functionality ratios can be used in the treatment of the genetic disorder. [0134] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times that of the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of individual functionality of the wild-type protein. [0135] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.5 times or less than 0.5 times than that of individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0136] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.4 times or less than 0.4 times than that of the individual functionality of the WT variant. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0137] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.3 times or less than 0.3 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0138] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0139] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0140] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0141] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1 selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0142] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1 selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual functionality of the WT protein variant. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0143] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1 selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0144] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1 selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351 is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0145] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R92P, S90G is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0146] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R92P, S90G is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein . [0147] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R92P, S90G is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0148] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R92P, S90G is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0149] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R92P, S90G, S90R, H117R, A137T, R141Q, H168R, H168P, P169S, Q171R and D263H is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0150] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R92P, S90G, S90R, H117R, A137T, R141Q, H168R, H168P, P169S, Q171R and D263H is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0151] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R92P, S90G, S90R, H117R, A137T, R141Q, H168R, H168P, P169S, Q171R and D263H is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT protein and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0152] In some embodiments, a variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1: R92P, S90G, S90R, H117R, A137T, R141Q, H168R, H168P, P169S, Q171R and D263H is provided. In some embodiments, when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. In some embodiments, the combined functionality of the WT and the variant protein is reduced by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, when compared to the individual functionality of the wild-type protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0 times than that of the individual functionality of the WT protein. In some embodiments, the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0153] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0154] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0155] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0 times than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual activity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower as compared to the individual activity of the WT protein. [0156] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual activity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual activity of the WT protein. [0157] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual activity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual activity of the WT protein. [0158] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0 times than that of the individual activity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual activity of the WT protein. [0159] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual stability of the WT protein. [0160] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual stability of the WT protein. [0161] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual stability of the WT protein. [0162] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0 times than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual stability of the WT protein. [0163] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual abundance of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual abundance of the WT protein. [0164] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual abundance of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual abundance of the WT protein. [0165] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual abundance of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual abundance of the WT protein. [0166] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0 times than that of the individual abundance of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual abundance of the WT protein. [0167] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual specificity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual specificity of the WT protein. [0168] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual specificity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual specificity of the WT protein. [0169] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual specificity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual specificity of the WT protein. [0170] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0 times than that of the individual specificity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual specificity of the WT protein. [0171] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual affinity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual affinity of the WT protein. [0172] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual affinity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual affinity of the WT protein. [0173] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual affinity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual affinity of the WT protein. [0174] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0 times than that of the individual affinity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual affinity of the WT protein. [0175] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. [0176] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. [0177] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. [0178] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein is ornithine transcarbamylase (OTC). [0179] In some embodiments, a composition comprising at least one protein variant of enhanced functionality is administered for the treatment of the genetic disorder. In some embodiments, the composition is administered once for the treatment of the genetic disorder. In some embodiments, the composition is administered more than once for the treatment of the genetic disorder. In some embodiments, a composition used in the first treatment and the composition used in the subsequent treatments comprise the same protein variants. In some embodiments, a composition used in the first treatment and the composition used in the subsequent treatments comprise different protein variants. In some embodiments, a composition used in the first treatment and the composition used in the subsequent treatments comprise a combination of same protein variants and different protein variants. [0180] In some embodiments, a composition comprising a protein variant or an expression vector encoding the protein variant described herein can be used in combination with other known agents and therapies. Administered "in combination", as used herein, means that two (or more) different treatments are delivered to the subject during the course of the subject's affliction with the disorder, e.g., the two or more treatments are delivered after the subject has been diagnosed with the disorder and before the disorder has been cured or eliminated or treatment has ceased for other reasons. In some embodiments, the delivery of one treatment is still occurring when the delivery of the second begins, so that there is overlap in terms of administration. This is sometimes referred to herein as "simultaneous" or "concurrent delivery". In other embodiments, the delivery of one treatment ends before the delivery of the other treatment begins. In some embodiments of either case, the treatment is more effective because of combined administration. For example, the second treatment is more effective, e.g., an equivalent effect is seen with less of the second treatment, or the second treatment reduces symptoms to a greater extent, than would be seen if the second treatment were administered in the absence of the first treatment, or the analogous situation is seen with the first treatment. In some embodiments, delivery is such that the reduction in a symptom, or other parameter related to the disorder is greater than what would be observed with one treatment delivered in the absence of the other. The effect of the two treatments can be partially additive, wholly additive, or greater than additive. The delivery can be such that an effect of the first treatment delivered is still detectable when the second is delivered. [0181] In some embodiments, the first treatment comprises administering a protein variant or a protein comprising a combination of point mutations to the subject. In one aspect, the subsequent treatments comprise, administering the same protein variant or the protein comprising the same combination of point mutations to the subject as the first treatment. In other embodiments, the subsequent treatments comprise, administering a different protein variant or the protein comprising a different combination of point mutations to the subject as the first treatment. [0182] In certain instances, the treatment with protein variants can be combined with other treatments such as dialysis, treatment with supplements of sugars, fats, and amino acids, medicines to remove extra ammonia, nitrogen, and combinations thereof. In some embodiments, excess ammonia is reduced by treating the subject with sodium benzoate, sodium phenylacetate, sodium phenylbutyrate or combinations thereof. In some embodiments, the genetic disorder is OTC deficiency. [0183] In some embodiments, the composition comprising the protein variant is administered to a subject having a genetic disorder in an amount effective to correct the genetic disorder or a symptom thereof in the subject. [0184] In some embodiments, the genetic disorder is OTC deficiency. [0185] In some embodiments, one or more expression vectors encoding a protein variant according to any of the embodiments is administered to a subject having a genetic disorder in an amount effective to correct the genetic disorder or a symptom thereof in the subject. [0186] In some embodiments, a variant sequence that is administered to a subject having a genetic disorder differs from the wild type sequence of SEQ ID NO:1 by 1 by substitution of 1 amino acid, 2, 3, 4, 5-10, 10-20, 20-30 or 30-40, 40-50, 50-60, 60-70 or 70- 80 amino acids. In some embodiments, a variant sequence can comprise the wild type sequence of Figure 1 and SEQ ID NO:1 with 1 residue, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more residues substituted. For example, 5, 10, 15, up to 20, up to 30 or up to 40, up to 50, up to 60, up to 70, up to 80 residues can be substituted. In some embodiments, one variant sequence comprising up to 5, 10, 15, 20, 30 or up amino acid substitutions can be administered. In other embodiments, a combination of variant sequences of SEQ ID NOS: 3-110 can be administered. In some embodiments, any one or more of the mutations listed in any one of Table 1 and/or 2 can be combined, including 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90100 or more of the point mutations listed in these tables. In some embodiments, any one or more of the loss of function mutants in tables 1 and/or 3 can be combined. [0187] In some embodiments, the subject is a mammal, such as a rodent (e.g. a guinea pig, a hamster, a rat, a mouse), murine (e.g. a mouse), canine (e.g. a dog), feline (e.g. a cat), equine (e.g. a horse), a primate, simian (e.g. a monkey or ape), a monkey (e.g. marmoset, baboon), an ape (e.g. gorilla, chimpanzee, orangutan, gibbon), or a human. In some embodiments, the subject is a human. In other embodiments, non-human mammals, especially mammals that are conventionally used as models for demonstrating therapeutic efficacy in humans (e.g. murine, primate, porcine, canine, or rabbit animals) is employed. In some embodiments, the subject is a fetus, neonate, juvenile or adult. In some embodiments, the subject has a total lack of Ornithine Transcarbamylase (OTC). In some embodiments the subject has a partial lack of Ornithine Transcarbamylase (OTC). In some embodiments, the subject is suspected of having OTC deficiency. A subject experiences symptoms consistent with a diagnosis of OTC deficiency. A subject does not experience any symptoms or exhibits symptoms not consistent with OTC deficiency. A subject can be diagnosed with OTC deficiency based on DNA sequencing-based methods. A subject can be diagnosed with OTC deficiency based on biochemical assays. A subject does not have OTC deficiency that is detectable by DNA sequencing-based methods and/or biochemical assays. In some embodiments, the subject is at a higher risk of having OTC deficiency. In some embodiments, the subject has a family history of OTC deficiency. In some embodiments, the subject has a genetic predisposition to OTC deficiency. In some embodiments, the subject is not at a higher risk of having OTC deficiency. [0188] In accordance with embodiments described herein, the composition comprising the protein variant can be administered by any suitable route of administration. Without limitation, the composition comprising the protein variant can be administered to the subject via oral administration, rectum administration, transdermal administration, intramuscular administration, intravenous administration, intranasal administration, or inhalation. In some embodiments, the composition comprising the protein variant is administered to liver cells. In other embodiments, the composition comprising the protein variant is administered into blood, spleen or lung. In some embodiments, the composition comprising the protein variant can be administered by injection or in the form of a tablet, capsule, or a drink. In some embodiments, the composition comprising the protein variants of the present invention can also be used for gene therapy, using standard gene delivery protocols. Methods for gene delivery are known in the art. See, e.g., U.S. Pat. Nos.5,399,346, 5,580,859, incorporated by reference herein in their entireties. In some embodiments, gene therapy is mediated by gene editing enzyme systems. Some non-limiting examples of the gene editing enzyme systems include CRISPR/Cas9 system, a zinc finger nuclease system, a transcription activator like effector nucleases (TALENs) system, a homing endonucleases (HE) system or a meganuclease system. [0189] As described herein, administration of a composition comprising the protein variant can correct, treat, inhibit, or ameliorate OTC deficiency or symptoms associated thereof. A few non-limiting examples of symptoms associated with OTC deficiency are vomiting, increased sleeping, progression to lethargy and coma, inability to feed, migraines, developmental delays and confusion. As disclosed herein, correct is used in a broad sense to refer to replacement or suppression of a protein variant associated with OTC deficiency. In some embodiments, replacement of a protein variant associated with OTC deficiency is performed by genetic therapy. In some embodiments, the protein variant is replaced by a wild- type protein. In other embodiments, the protein variant is replaced by a highly functional protein variant. As disclosed herein, amelioration is used in a broad sense to refer to at least a reduction in the magnitude of a parameter, e.g., symptom, associated with the pathological condition being treated. In some embodiments, the method can completely inhibit, e.g., prevented from happening, or stopped, e.g., terminated, such that the host no longer suffers from the pathological condition, or at least one or more of the symptoms that characterize the pathological condition. In some embodiments, the method can delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. [0190] When an “effective amount” is indicated, the precise amount of the compositions of the present invention to be administered can be determined by a physician with consideration of individual differences in age, gender, weight, extent of symptoms, progression of disease, and condition of the subject. [0191] In some embodiments, a method of enhancing the functionality of Ornithine transcarbamylase (OTC) protein in a subject is provided. The method comprises administering to the subject the protein or composition, wherein the OTC deficiency or a symptom thereof is reduced after administration. [0192] In some embodiments, enhancing the functionality of OTC can enhance the abundance, activity, specificity, binding affinity of OTC or a combination of the aforementioned parameters. In some embodiments, the activity of the protein can comprise but not limited to enzymatic activity, non-enzymatic activity, catalytic activity, non-catalytic activity and binding activity. In some embodiments, the functionality of OTC protein in the subject before administration is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, lower than the functionality of the wild-type protein. In some embodiments, the ratio of functionality between the wild-type protein and the protein variant before administration is 0.95, 0.94, 0.93, 0.92, 0.91 or lower. In some embodiments, the functionality of the OTC protein is increased after administration by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, more than the functionality of the wild-type protein. In some embodiments, the ratio of functionality of the protein variant to wild-type protein after administration is 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2 or higher. [0193] In some embodiments, the subject is a fetus, neonate, juvenile or adult. [0194] In some embodiments, a method of administering one or more expression vectors to a subject in an amount to correct the OTC deficiency or a symptom thereof in the subject is provided. [0195] In some embodiments, the OTC is modified to exhibit an enhanced function. [0196] In some embodiments, the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 to exhibit an enhanced function. [0197] In some embodiments, the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110. [0198] In some embodiments, the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 [0199] In some embodiments, the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 5% when compared to the function of WT protein of SEQ ID NO:1. [0200] In some embodiments, the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 50% when compared to the function of WT protein of SEQ ID NO:1. [0201] In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 25% when compared to the function of WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of WT protein of SEQ ID NO:1. [0202] In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 50% when compared to the function of WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 50% when compared to the function of WT protein of SEQ ID NO:1. [0203] In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 30% when compared to the function of WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 40% when compared to the function of WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 50% when compared to the function of WT protein of SEQ ID NO:1. [0204] In some embodiments, the function of the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 30% when compared to the function of WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 40% when compared to the function of WT protein of SEQ ID NO:1. In some embodiments, the function of the protein with at least one of the point mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C listed in Tables 1 and/or 2 is enhanced by at least 50% when compared to the function of WT protein of SEQ ID NO:1. [0205] In some embodiments, the function of the OTC protein is enhanced by at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any values in between 5% and 400%. In some embodiments, the functionality of OTC protein in the subject before administration is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, lower than the functionality of the wild-type protein. In some embodiments, the ratio of functionality of the protein variant to wild-type protein before administration is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower. In some embodiments, the functionality of the OTC protein is increased after administration by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, more than the functionality of the wild-type protein. In some embodiments, the ratio of functionality of the protein variant to wild-type protein after administration is 1, 1.01, 1.02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2, 1.3, 1.4 or higher. In some embodiments, a subject with a mutant protein that is lower than wild-type (e.g., any of the 0.95 values or lower in the tables in the present document) can be remedied by adding a mutant protein that is higher than wild type (e.g., any of the 1.0 or higher values in the tables of the present document). In some embodiments, a subject with a mutant protein that is lower than wild-type (e.g., any of the 0.95 values or lower in the tables in the present document) can be remedied by adding a mutant protein that is higher than wild type (e.g., any of the 1.2 or higher values in the tables of the present document). In some embodiments, a subject with a mutant protein that is lower than wild-type (e.g., any of the 0.95 values or lower in the tables in the present document) can be remedied by adding a mutant protein that is higher than wild type (e.g., any of the 1.25 or higher values in the tables of the present document). In some embodiments, a subject with a mutant protein that is lower than wild-type (e.g., any of the 0.95 values or lower in the tables in the present document) can be remedied by adding a mutant protein that is higher than wild type (e.g., any of the 1.3 or higher values in the tables of the present document). [0206] In some embodiments, the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 to exhibit an enhanced stability. [0207] In some embodiments, the OTC is replaced or supplemented by one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C to exhibit an enhanced stability. [0208] In some embodiments, the stability of the OTC protein is enhanced by at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400% or any values in between 5% and 400%. In some embodiments, the stability of OTC protein in the subject before administration is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, lower than the stability of the wild-type protein. In some embodiments, the ratio of stability of the protein variant to wild-type protein before administration is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower. In some embodiments, the stability of the OTC protein is increased after administration by at least 1%, 5% 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 250%, 300%, 400% or any integer that is between 1 and 400%, more than the stability of the wild-type protein. In some embodiments, the ratio of stability of the protein variant to wild-type protein after administration is 1, 1.01, 1,02, 1.03, 1.04, 1.05, 1.1, 1.15, 1.2, 1.3, 1.4 or higher. [0209] In some embodiments, a kit for determining a specific mode of treatment of a genetic disorder is provided. The kit comprises a look up table. The look up table indicates specific amino acid substitutions that are commonly involved in a cellular mechanism; and one or more vectors comprising sequences of SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 is provided. [0210] In some embodiments, the look up table comprising a list of mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the table contains mutations that confer reduced activity and/or stability to the protein. (table 3 or those in table 1 with lower than 0.95 ratio). In some embodiments, the table contains mutations that confer increased activity and/or stability to the protein (those in table 2 or those in table 1 with 1.05 or greater than 1.05). [0211] In some embodiments, the look up table comprising a list of mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the look up table comprising a list of mutations as follows: T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is provided. In some embodiments, the table contains mutations that confer reduced activity and/or stability to the protein. (table 3 or those in table 1 with lower than 0.95 ratio). In some embodiments, the table contains mutations that confer increased activity and/or stability to the protein (those in table 2 or those in table 1 with 1.05 or greater than 1.05). In some embodiments, the table contains mutations that confer increased activity and/or stability to the protein (those in table 2 or those in table 1 with 1.2 or greater than 1.2). In some embodiments, the table contains mutations that confer increased activity and/or stability to the protein (those in table 2 or those in table 1 with 1.25 or greater than 1.25). In some embodiments, the table contains mutations that confer increased activity and/or stability to the protein (those in table 2 or those in table 1 with 1.3 or greater than 1.3). In some embodiments, the table contains mutations that confer increased activity and/or stability to the protein (those in table 2 or those in table 1 with 1.4 or greater than 1.4). [0212] In some embodiments, a kit for identifying proteins with specific amino acid substitutions is provided. The kit comprises a lookup table. In some embodiments, the look up table indicates proteins with specific amino acid substitutions that exhibit dominant negative interactions with a wildtype protein of SEQ ID NO:1. [0213] In some embodiments, the look up table comprising a list of mutations as follows: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L is provided. [0214] In some embodiments, the lookup table contains mutations that exhibit a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the mutant is 0.8 times or less than 0.8 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the mutant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the mutant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. [0215] In some embodiments, the lookup table lists a panel comprising a plurality of protein variants and their effect on functionality of protein. In some embodiments, the look up table can be referred to provide information on amino acid substitution that has a dominant negative interaction with WT protein. In some embodiments, the lookup table can be referred to select an amino acid substitution that reduces, alleviates, or limits the symptoms associated with the genetic disorder. In other embodiments, the look up table can be referred to provide functional information to select alternative functional amino acid substitutions when reverting a pathogenic amino acid substitution mutation back to the reference amino acid is not possible. A region of the protein can be selected where the frequency of amino acid substitution is significantly greater in subjects with the genetic disorder than found in a reference population without the disorder. In some embodiments, the look up table can be referred to limit a region of protein for gene therapy. [0216] In some embodiments, the genetic disorder is OTC deficiency. [0217] In some embodiments, a method of identifying a subject having a genetic disorder is provided. The method comprises detecting a presence of at least one mutation in the protein that is different in the subject with the genetic disorder as compared to a subject without the disorder, wherein the presence of at least one mutation indicates the presence of the genetic disorder in the subject. [0218] In some embodiments, a method for identifying a subject having a genetic disorder is provided. The method comprises detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disease that exhibits dominant negative interactions with a wildtype protein of SEQ ID NO:1, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject. [0219] In some embodiments, the presence of at least one mutation can be used to indicate the presence of the genetic disorder in high-risk patient population earlier than is possible for existing methods of genetic disorder detection. In some embodiments, the presence of at least one mutation can be used to indicate the presence of genetic disorder in subjects who are not at risk of developing the genetic disorder. In some embodiments, the presence of at least one mutation in the subject indicates that the subject is genetically pre-disposed to developing the genetic disorder. In some embodiments, the presence of at least one mutation in the subject indicates that the subject is at the early stages of developing the genetic disorder. In some embodiments, the presence of at least one mutation in the subject indicates that the subject is at an advanced stage of genetic disorder. [0220] In some embodiments, the ratio of functionality of the wild-type protein and the protein variant with at least one mutation that is detected in the subject is 0.95 or less than 0.95. In some embodiments, the ratio of functionality of the wild-type protein and the protein variant with at least one mutation that is detected in the subject is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower as listed in Tables 1 and/or 3. [0221] In some embodiments, one or more regions of the protein can comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80 or more of amino acid substitutions. Many of these amino acid substitutions can be clinically actionable, such that an observed anomaly can be indicative of a genetic disorder. In some embodiments, the anomaly can be a decreased function of a protein as compared to normal reference subjects. In some embodiments, the anomaly can be a decreased stability of a protein as compared to normal reference subjects. [0222] In some embodiments, a method of improving, ameliorating, or treating a genetic disorder is provided. The method comprises detecting a presence of at least one mutation in the protein that is different in the subject with the genetic disorder as compared to a subject without the disorder, wherein the presence of at least one mutation indicates the presence of the genetic disorder in the subject. The method also comprises administering to the subject at least one protein variant or composition provided herein in the embodiments, wherein the genetic disorder or a symptom thereof is reduced after administration. [0223] In some embodiments, a method of improving, ameliorating, or treating a genetic disorder is provided. The method comprises detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder that exhibits dominant negative interactions with a wildtype protein of SEQ ID NO:1, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject. The method also comprises administering to the subject the protein or composition disclosed herein, wherein the genetic disorder or a symptom thereof is reduced after administration. In some embodiments, the subject is a fetus, neonate, juvenile or adult. [0224] In some embodiments, the mutation to be detected is selected from a group consisting of: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I is provided. [0225] In some embodiments, the mutants provided herein are mutants that result in protein variants of reduced activity and/or stability. [0226] In some embodiments, the mutants are classified as mutants that result in protein variants of reduced activity and/or stability if the ratio of activity of the protein variant to the wild-type protein is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower. [0227] In some embodiments, the mutants are classified as mutants that result in protein variants of reduced activity and/or stability if the ratio of activity of the protein variant to the wild-type protein is less than 1. [0228] In some embodiments, the functionality of the mutants that result in protein variants of reduced activity and/or stability is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, less than the functionality of the wild-type protein. In some embodiments, the ratio of functionality of the protein variant to the wild-type protein is 0.95 or less than 0.95. In some embodiments, the ratio of functionality of the protein variant of reduced activity and/or stability to the wild-type protein is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower as listed in Tables 1 and/or 3. [0229] In some embodiments, the activity of the mutants that result in protein variants of reduced activity and/or stability is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, , less than the activity of the wild-type protein. In some embodiments, the ratio of activity of the protein variant to the wild-type protein is 0.95 or less than 0.95. In some embodiments, the ratio of activity of the protein variant of reduced activity and/or stability to the wild-type protein is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower. In some embodiments, the activity of the protein can comprise but not limited to enzymatic activity, non-enzymatic activity, catalytic activity, non-catalytic activity and binding activity. [0230] In some embodiments, the expression of the mutants that result in protein variants of reduced activity and/or stability is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, less than the expression of the wild-type protein. In some embodiments, the ratio of expression of the protein variant to the wild-type protein is 0.95 or less than 0.95. In some embodiments, the ratio of expression of the protein variant of reduced activity and/or stability to the wild-type protein is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower. [0231] In some embodiments, the abundance of the mutants that result in protein variants of reduced activity and/or stability is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, less than the abundance of the wild-type protein. In some embodiments, the ratio of abundance of the protein variant to the wild-type protein is 0.95 or less than 0.95. In some embodiments, the ratio of abundance of the protein variant of reduced activity and/or stability to the wild-type protein is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower. [0232] In some embodiments, the specificity of the mutants that result in protein variants of reduced activity and/or stability is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, less than the specificity of the wild-type protein. In some embodiments, the ratio of specificity of the protein variant to the wild-type protein is 0.95 or less than 0.95. In some embodiments, the ratio of specificity of the protein variant of reduced activity and/or stability to the wild-type protein is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower. [0233] In some embodiments, the affinity of the mutants that result in protein variants of reduced activity and/or stability is at least 0%, 1%, 5% 10%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or any integer that is between 1 and 95%, less than the affinity of the wild-type protein. In some embodiments, the ratio of affinity of the protein variant to the wild-type protein is 0.95 or less than 0.95. In some embodiments, the ratio of affinity of the protein variant of reduced activity and/or stability to the wild-type protein is 0.95, 0.9, 0.85, 0.8, 0.75, 0.7, 0.6 or lower. [0234] In some embodiments, mutants that result in protein variants of reduced activity and/or stability exhibit a change in functionality, abundance, activity, specificity, affinity or a combination of the aforementioned parameters as compared to the wild-type. [0235] In some embodiments, the presence of one or more mutants that result in protein variants of reduced activity and/or stability in the subject can indicate the presence of a genetic disorder in the subject. In some embodiments, a composition comprising one or more mutants that result in protein variants of increased activity and/or stability as provided in the embodiments is administered to the subject with the genetic disorder. In some embodiments, the administration of one or more mutants that result in protein variants of increased activity and/or stability can replace one or more mutants that result in protein variants of reduced activity and/or stability in the subject. In other embodiments, the administration of one or more mutants that result in protein variants of increased activity and/or stability can suppress one or more mutants that result in protein variants of reduced activity and/or stability in the subject. In other embodiments, the administration of one or more mutants that result in protein variants of increased activity and/or stability can enhance the functionality of the mutants that result in protein variants of reduced activity and/or stability in the subject. [0236] In some embodiments, the genetic disorder is OTC deficiency. [0237] In some embodiments, the presence of at least one mutation that indicates the presence of genetic disorder in the subject is selected from the mutations in Table 3. [0238] In some embodiments, an engineered protein administered to the subject includes one or more of the mutations in Table 2. [0239] In some embodiments, a method of screening for a protein variant is provided. The method comprises providing a population of yeast strains each expressing a protein of the embodiments disclosed herein, growing the yeast strains on a minimal growth medium, screening the population of yeast strains expressing the protein variant for growth based on a growth score, identifying the protein variant based on the growth score that was screened for and identifying a specific region or a position with an amino acid substitution of the protein variant that was identified based on the growth score, wherein the growth score of the protein variant is higher than the growth score of the WT protein. [0240] In some embodiments, the identified position with an amino acid substitution is further substituted with another amino acid. [0241] In some embodiments, the identified position with an amino acid substitution is further substituted with a conservative amino acid. In some embodiments, the identified position with an amino acid substitution is further substituted with a non- conservative amino acid. [0242] In some embodiments, a method of screening for a protein variant is provided. The method comprises providing a population of yeast strains each expressing a protein of the embodiments disclosed herein, growing the yeast strains on a minimal growth medium, screening the population of yeast strains expressing the protein variant for growth based on a growth score, identifying the protein variant based on the growth score that was screened for and functionally classifying the identified protein variants based on the growth score. [0243] In some embodiments, a method of screening for a protein variant that exhibits dominant negative interaction with a wildtype protein is provided. The method comprises providing a population of haploid yeast strains each expressing a protein of the embodiments disclosed herein, mixing the population of haploid yeast strains expressing the protein variant with a haploid yeast strain expressing a WT protein to generate a population of diploid yeast strains each expressing a variant protein in combination with the WT protein, growing the diploid yeast strains on a minimal growth medium, screening the population of diploid yeast strains expressing a variant protein in combination with the WT protein for growth based on a growth score and identifying a protein variant that exhibits dominant negative interactions with a wildtype protein based on the growth score that was screened for. [0244] In some embodiments, the yeast is a budding yeast. In some embodiments, a yeast that relies on sexual agglutination for mating is used. In some embodiments, the yeast is Saccharomyces cerevisiae. In some embodiments, the yeast is selected from Saccharomyces exiguous, Saccharomyces eubayanus, Saccharomyces pastorianus, Schizosaccharomyces pombe, or combinations thereof. In some embodiments, the yeast is haploid. In some embodiments, the yeast is diploid. In some embodiments, the yeast is MATa. In some embodiments, the yeast is MATĮ. In some embodiments, the yeast is MATa/Į. [0245] In some embodiments, the yeast strains are grown in a liquid growth medium. In some embodiments, the yeast cells are grown in a solid growth medium. In some embodiments, the yeast strains are grown in the liquid growth medium and solid growth medium. In some embodiments, the yeast strains are grown for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 22, 24, 25, 26, 27, 28, 29, 30, 35, 40 hours, or any number of hours that is between 1 and 40. In some embodiments, the year strains are grown for 1, 2, 3, 4, 5 days, or any number of days that is between 1 and 5. In some embodiments, the yeast strains are grown at 27° C. In some embodiments, the yeast strains are grown at 30° C. In some embodiments, the yeast strains are grown at 37° C. In some embodiments, the yeast strains are grown at 20, 22, 23, 24, 25, 26, 28, 29, 31, 32, 33, 34, 35, 36, 38, 40° C or any temperature that is between 20 and 40° C. In some embodiments, the yeast strains are grown at a particular temperature and are subsequently shifted to be grown at a lower temperature. In some embodiments, the yeast strains are grown at a particular temperature and are subsequently shifted to be grown at a higher temperature. [0246] In some embodiments, the minimal growth medium lacks arginine. In some embodiments the minimal growth medium lacks an amino acid. In some embodiments, the minimal growth medium lacks arginine (Arg). In some embodiments, the minimal growth medium lacks one or more of aspartic acid (Asp), lysine (Lys), proline (Pro), glutamic acid (Glu), alanine (Ala), methionine (Met), serine (Ser), threonine (Thr), glycine (Gly), asparagine (Asn), isoleucine (Ile), leucine (Leu), phenylalanine (Phe), valine (Val), tryptophan (Trp), tyrosine (Tyr), glutamine (Gln), histidine (His), cysteine (Cys); a derivative thereof; or a salt thereof. [0247] In some embodiments, the yeast strains expressing the protein variant are screened based on a growth score. In some embodiments, the growth score of the protein variant is relative to the growth score of the wild type protein. [0248] In some embodiments, the growth score of the protein variant is higher than the growth score of the WT protein. In some embodiments, the growth score of the protein variant is lower than the growth score of the WT protein. In some embodiments, the growth score of the protein variant is the same as the growth score of the WT protein. [0249] In some embodiments, the growth score of the variant is 1 or lower than 1. In some embodiments, the growth score of the variant is 1 or greater than 1. In some embodiments, the growth score of the variant is 0, 0.001, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2 or higher. [0250] In some embodiments, the variant is identified based on the growth score that was screened for. In some embodiments, the growth score of the protein variant is higher than the growth score of the WT protein. In some embodiments, the ratio of the growth score of the variant to wild-type is 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10 or higher. In some embodiments, the growth score of the protein variant is lower than the growth score of the WT protein. In some embodiments, the ratio of the growth score of the variant to wild-type is 0, 0.001, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 0.96, 0.97, 0.98, 0.99 or lower. [0251] In some embodiments, the identified protein variants are functionally classified based on the growth score. In some embodiments, the protein variants are classified as variants exhibiting an enhanced function if the ratio of the growth score of the variant to wild-type is 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10 or higher. In some embodiments, the protein variants are classified as variants exhibiting a reduced function if the ratio of the growth score of the variant to wild-type is 0, 0.001, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 0.96, 0.97, 0.98, 0.99 or lower. In some embodiments, the protein variants are classified as variants exhibiting an enhanced activity if the ratio of the growth score of the variant to wild-type is 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10 or higher. In some embodiments, the protein variants are classified as variants exhibiting a reduced activity if the ratio of the growth score of the variant to wild-type is 0, 0.001, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 0.96, 0.97, 0.98, 0.99 or lower. [0252] In some embodiments, the protein variants are classified as variants exhibiting an enhanced specificity if the ratio of the growth score of the variant to wild-type is 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10 or higher. In some embodiments, the protein variants are classified as variants exhibiting a reduced specificity if the ratio of the growth score of the variant to wild-type is 0, 0.001, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 0.96, 0.97, 0.98, 0.99 or lower. In some embodiments, the protein variants are classified as variants exhibiting an enhanced affinity if the ratio of the growth score of the variant to wild-type is 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10 or higher. In some embodiments, the protein variants are classified as variants exhibiting a reduced affinity if the ratio of the growth score of the variant to wild-type is 0, 0.001, 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 0.96, 0.97, 0.98, 0.99 or lower. [0253] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0254] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0255] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0256] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0 times than that of the individual functionality of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality of the WT protein. [0257] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual activity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual activity of the WT protein. [0258] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual activity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual activity of the WT protein. [0259] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual activity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual activity of the WT protein. [0260] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0 times than that of the individual activity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined activity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual activity of the WT protein. [0261] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual abundance of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual abundance of the WT protein. [0262] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual abundance of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual abundance of the WT protein. [0263] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual abundance of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual abundance of the WT protein. [0264] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0 times than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined stability of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual stability of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0 times than that of the individual abundance of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined abundance of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual abundance of the WT protein. [0265] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual specificity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual specificity of the WT protein. [0266] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual specificity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual specificity of the WT protein. [0267] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual specificity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual specificity of the WT protein. [0268] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0 times than that of the individual specificity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined specificity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual specificity of the WT protein. [0269] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual affinity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual affinity of the WT protein. [0270] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual affinity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual affinity of the WT protein. [0271] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual affinity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual affinity of the WT protein. [0272] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0 times than that of the individual affinity of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined affinity of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual affinity of the WT protein. [0273] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8 times or less than 0.8 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. [0274] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.2 times or less than 0.2 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. [0275] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.1 times or less than 0.1 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. [0276] In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0 times than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. In some embodiments, the protein variant exhibits a dominant negative interaction with the WT protein if the ratio of combined functionality, specificity, abundance, activity, affinity or combination thereof of the wild-type protein and the protein variant is 0.8, 0.75, 0.7, 0.65, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, 0.05, 0.04, 0.03, 0.02, 0.01, 0.001, 0 times or lower than that of the individual functionality, specificity, abundance, activity, affinity or combination thereof of the WT protein. Development of an assay for determining high functional protein variants [0277] As provided herein, an assay was developed to determine the impact of different protein variants on the functionality and stability of OTC. [0278] A construct encoding the protein variant can be used for expression in a yeast system that has been knocked out of the yeast homolog. For example, the yeast can be genetically engineered to have the gene ARG3, the yeast ortholog of human OTC protein, knocked out. The yeast can then be genetically engineered to express OTC from a nucleic acid. Expression constructs for yeast are known by those of skill in the art and may have a strong yeast promoter/terminator and may comprise a yeast selectable marker cassette. [0279] An assay can then be run to determine the yeast cells growth in comparison to a yeast cell expressing the wild type OTC or a yeast cell expressing a OTC gene that has no mutations. Loss of function or enhanced functionality of the yeast enzymes produces a quantitative and easily measured trait, poor growth in the absence of arginine supplementation. Kits [0280] Also provided herein are kits including the expression constructs, and protein sequences provided and described herein as well as written instructions for making and using the same. Thus, for example, provided herein is a kit comprising one or more of: a protein sequence as described herein; and/or an expression construct as described herein. [0281] A look up table is also provided for use with the kit to assess the combination of mutations that indicate enhanced functionality or stability. The look-up table is a table that correlates one form of data to another form, or one or more forms of data to a predicted outcome to which the data is relevant, such as phenotype or trait. For example, a look-up table can comprise a correlation between allelic data for at least one protein that is involved in a metabolic pathway and a particular trait or phenotype, such as a particular disease diagnosis, that an individual who comprises the particular allelic data is likely to display, or is more likely to display than individuals who do not comprise the particular allelic data. Look- up tables can be multidimensional, for example, without being limiting, they can contain information about multiple alleles for a particular protein or proteins simultaneously, or they can contain information about multiple protein variants, such as mutational variants, and they can also comprise other factors, such as particulars about diseases diagnoses, therapeutic methods or drugs to be used with a particular disease. In some embodiments, the look-up table comprises correlations between at least one allele and a disease. [0282] A look-up table can be generated by the individual assessment of protein variants or by studies of cells that have the mutated form of the protein that is to be tested. [0283] Some embodiments of the present disclosure provided herein are described by way of the following exemplary numbered arrangements: 1. A protein having the amino acid sequence of any one of the SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110. 2. A protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C. 3. The protein of arrangements 1-2, wherein the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C exhibits higher activity when compared to the WT protein of SEQ ID NO:1. 4. The protein of any of the preceding arrangements, wherein the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 5% when compared to the function of wild-type protein of SEQ ID NO:1. 5. The protein of any of the preceding arrangements, wherein the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10% when compared to the function of wild-type protein of SEQ ID NO:1. 6. The protein of any of the preceding arrangements, wherein the point mutants comprise at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351. 7. A protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence), comprising one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C. 8. The protein of arrangement 7, wherein the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C exhibits higher activity when compared to the WT protein of SEQ ID NO:1. 9. The protein of arrangements 7-8, wherein the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 10% when compared to the function of wild-type protein of SEQ ID NO:1. 10. The protein of arrangements 7-9, wherein the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 50% when compared to the function of wild-type protein of SEQ ID NO:1. 11. The protein of arrangements 7-10, wherein the point mutants comprise at least one amino acid change at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 53, 120, 124, 143, 211, 266, 324, 325, 326, 350. 12. An expression vector comprising a polynucleotide sequence encoding for one or more of the proteins in any one or more of arrangements 1-11. 13. The expression vector of arrangement 12, wherein the sequence is a codon-optimized sequence. 14. The expression vector of arrangement 13, wherein the polynucleotide sequence comprises one or more of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 5% when compared to the function of wild-type protein of SEQ ID NO:1. 15. The expression vector of arrangement 13, wherein the polynucleotide sequence comprises one or more of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of wild-type protein of SEQ ID NO:1. 16. A composition of any of the preceding arrangements, wherein the protein is ornithine transcarbamylase (OTC). 17. A composition of any of the preceding arrangements, for use in the treatment of a genetic disorder. 18. A composition of any of the preceding arrangements, wherein the composition is administered to a subject having a genetic disorder in an amount effective to correct the genetic disorder or a symptom thereof in the subject. 19. A composition of arrangements 16-18, wherein the genetic disorder is OTC deficiency. 20. A method of enhancing the functionality of Ornithine transcarbamylase (OTC) protein in a subject, the method comprising: administering to the subject the protein or composition of any one of arrangements 1-19, wherein the OTC deficiency or a symptom thereof is reduced after administration. 21. The method of arrangement 20, wherein the subject is a fetus, neonate, juvenile or adult. 22. The method of arrangement 20, wherein one or more expression vectors is administered to a subject in an amount effective to correct the OTC deficiency or a symptom thereof in the subject. 23. The method of arrangement 20, wherein the OTC is modified to exhibit an enhanced function. 24. The method of arrangement 20, wherein the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 to exhibit an enhanced function. 25. The method of arrangement 20, wherein the OTC is replaced or supplemented by one or more polynucleotide sequences encoding SEQ ID NOS: SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110. 26. The method of arrangements 20-25, wherein the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 5% when compared to the function of WT protein of SEQ ID NO:1. 27. The method of arrangements 20-25, wherein the function of the protein with at least one of the point mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143Cis enhanced by at least 50% when compared to the function of WT protein of SEQ ID NO:1. 28. The method of arrangements 20-25, wherein the function of the protein with at least one of the point mutations as follows: Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C is enhanced by at least 25% when compared to the function of WT protein of SEQ ID NO:1. 29. A method of screening for a protein variant, the method comprising: a) providing a population of yeast strains each expressing a protein of arrangements 1-11; b) growing the yeast strains on a minimal growth medium; c) screening the population of yeast strains expressing the protein variant for growth based on a growth score; d) identifying the protein variant based on the growth score that was screened for; and e) identifying a specific region or a position with an amino acid substitution of the protein variant that was identified based on the growth score, wherein the growth score of the protein variant is higher than the growth score of the WT protein. 30. The method of arrangement 29, wherein the position with an amino acid substitution is further substituted with another amino acid. 31. A method of screening for a protein variant, the method comprising: a) providing a population of yeast strains each expressing a protein of arrangements 1-11; b) growing the yeast strains on a minimal growth medium; c) screening the population of yeast strains expressing the protein variant for growth based on a growth score; d) identifying the protein variants based on the growth score that was screened for; and e) functionally classifying the identified protein variants based on the growth score. 32. The method of arrangement 31, wherein the growth score of the protein variant is higher than the growth score of the WT protein, lower than the growth score of the WT protein, or the same as the growth score of the WT protein. 33. A kit for determining a specific mode of treatment of a genetic disorder comprising: a look up table, wherein the look up table indicates specific amino acid substitutions that are commonly involved in a cellular mechanism; and one or more vectors comprising sequences of SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110. 34. The kit of arrangement 33, wherein the look up table comprises a list of mutations as follows: G83V, T127S, T44S, F110I, Q285R, T125A, N33D, Q78K, K275E, K275Q, G50A, S146A, F110C, R89S, I116V, L251M, T262A, D297N, F110V, Q69H, I204L, K54Q, N121D, M268I, D126E, Q270K, T113I, N47D, M84L, F65Y, Q279K, T125S, Q180L, P108T, K351M, L124V, A227P, R89T, Q279E, F101L, K351Q, F101V, N121S, T230I, I266V, F101C, G83C, K274R, I204F, L124F, I334T, T97I, T150N, S96A, V120L, G100A, S81T, H117Q, Y284F, Q270E, K243R, K289E, T262S, G83A, V130L, I172V, K292E, T125K, N198S, L163M, G257A, V286I, S267G, A217V, L124I, I53M, Q114E, H255R, I266L, V120E, K307T, V120A, F101I, P325S, F211L, M134V, Y143H, E326Q, P325T, M56L, S340A, Q285K, T333A, F211V, F324I, V120G, T264S, Q350P, Q350E, Y143D, I53L, F324V, L349I, I266M, E326A, P325A, Y143S, Y143C 35. The kit of arrangement 33, wherein the genetic disorder is OTC deficiency. 36. A method of identifying a subject having a genetic disorder, the method comprising: detecting a presence of at least one mutation in the protein that is different in the subject with a genetic disorder as compared to a subject without the disorder, wherein the presence of at least one mutation indicates the presence of a genetic disorder in the subject. 37. A method of improving, ameliorating, or treating a genetic disorder, the method comprising: detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject; and administering to the subject the protein or composition of any one of arrangements 1-19, wherein the genetic disorder or a symptom thereof is reduced after administration. 38. The method of one of arrangements 36 or 37, wherein the mutation is selected from a group consisting of: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191I. 39. The method of arrangements 36-38, wherein the genetic disorder is OTC deficiency. 40. The method of one of arrangements 36 or 37, wherein the one mutation that indicates the presence of genetic disorder in the subject is selected from the mutations in Table 3. 41. The method of arrangement 40, wherein an engineered protein administered to the subject includes one or more of the mutations in Table 2. 42. A variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1, selected from the group consisting of any one of the mutations: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L, wherein when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. 43. A variant protein that is at least 80% identical to SEQ ID NO: 1(WT Sequence) comprising one or more of the point mutations at the amino acid positions of SEQ ID NO:1, selected from the group consisting of 33, 44, 47, 50, 53, 54, 56, 65, 69, 78, 81, 83, 84, 89, 96, 97, 100, 101, 108, 110, 113, 114, 116, 117, 120, 121, 124, 125, 126, 127, 130, 134, 143, 146, 150, 163, 172, 180, 198, 204, 211, 217, 227, 230, 243, 251, 255, 257, 262, 264, 266, 267, 268, 270, 274, 275, 279, 284, 285, 286, 289, 292, 297, 307, 324, 325, 326, 333, 334, 340, 349, 350, 351, wherein when the variant protein is contacted with a WT protein of SEQ ID NO: 1, the combined functionality of the WT protein and the variant protein is reduced by at least 20% when compared to the individual functionality of the WT protein. 44. A composition of arrangements 42-43, wherein the protein is ornithine transcarbamylase (OTC). 45. A method for identifying a subject having a genetic disorder, the method comprising: detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder that exhibits dominant negative interactions with a wildtype protein of SEQ ID NO:1, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject. 46. A method of improving, ameliorating, or treating a genetic disorder, the method comprising: detecting the presence of at least one mutation in the protein that is different in the subject with genetic disorder as compared to a subject without the disorder that exhibits dominant negative interactions with a wildtype protein of SEQ ID NO:1, wherein the presence of at least one mutation indicates the presence of genetic disorder in the subject; and administering to the subject the protein or composition of any one of arrangements 1-19, wherein the genetic disorder or a symptom thereof is reduced after administration. 47. The method of arrangement 45 or 46, wherein the subject is a fetus, neonate, juvenile or adult. 48. The method of arrangement 45-47, wherein the mutation is selected from R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L. 49. A kit for identifying proteins with specific amino acid substitutions comprising: a look up table, wherein the look up table indicates proteins with specific amino acid substitutions that exhibit dominant negative interactions with a wildtype protein of SEQ ID NO:1. 50. The kit of arrangement 49, wherein the look up table comprises a list of mutations as follows: R141Q, H302D, L139S, P305L, C303Y, D297A, A253E, C303W, L244P, A291D, S203F, H302L, G106R, H302P, Y176S, R330S, R141L, C303F, T242I, P347R, V323E, T242P, D41E, L191R, A208P, H202L, A254E, L201Q, A137E, L151Q, R141G, W298L, V311G, Q180P, M84K, A140D, I204S, A253T, E326K, L186P, H182D, L342R, S203P, W193R, D297V, I200F, A294P, P347S, W298G, R320L, Y183D, A253P, L151R, P250R, L63Q, D297Y, A237V, A233E, V259E, V138E, A327P, P169T, A152P, Q235P, W332L, A336T, Q171R, S192N, T93R, E181V, R141P, L37Q, M205V, M206K, G39V, A291P, T343R, V286G, S340P, A233V, L304V, T262R, T299P, L104P, K64I, Y284S, G195E, S60P, V315D, H168R, W332R, L45V, L43H, Y284D, R320P, T44P, D115V, A336D, G106V, T93K, W332S, D263V, A254P, S321L, L45Q, G188V, G100R, K210I, A209V, L322V, L173P, L77W, R66G, H214Y, N161I, V286A, L342P, G100D, L341P, S60L, G83R, V323L, D263A, H182P, L104R, N329Y, A233P, T290P, T247I, A208T, D263Y, D41V, W298S, E98K, G257R, L45R, S340Y, V311L, L59P, L57P, T97K, D297H, V259G, R330I, Y176D, P347L, T178R, S164P, L179R, L186Q, P169S, E52V, W332G, A61P, K64Q, T190P, L322P, Y183S, L177R, T333R, G256V, W332C, R40P, P220S, A217E, D115A, S164L, M134R, L148W, H302Y, N329S, N240D, G197V, L43P, M335K, L76S, P169R, P169H, A237P, N329T, M338R, P347H, I53N, T219P, D249G, L189F, L77S, M205K, T343P, M84R, T230P, L246P, H168D, V339G, N161D, F211Y, S96P, R92P, I85N, L260S, L191F, D41Y, H168L, D62Y, T247P, L118W, K64N, L173R, P169A, G105V, S90R, T247K, M206R, G106E, I261N, S207R, T333K, S318T, L189H, M205I, Q216P, G162W, L215H, W298R, L43F, T97P, N161K, K64R, L42R, F281V, E87K, L42H, L45P, G212V, R92Q, K64T, Y345C, K64E, L37P, L37R, F48S, G79V, A137P, C109R, A336V, L201P, T262P, A217G, E181G, D263H, L43R, A237D, H168Y, A294D, W193G, G162V, V286D, R330G, L42P, P108R, A152D, R330T, L63R, P225R, M213K, G195R, D136V, P347T, N329D, Y345D, E52G, L173Q, E310K, F316S, M56R, T247R, D62A, L57R, R92G, P305H, P220T, Y223D, D136Y, T97R, L82S, A218V, Y345S, P158R, D62V, Q145K, H168P, N161Y, I194N, G188C, N329I, S321P, I53F, L63P, Q171P, Q145R, M205R, G197E, K210T, V337D, P75L, D115N, N329H, N161T, S164A, S207C, G195W, I53S, M56K, Q171K, P158T, L301S, A295P, T178M, H182L, V229G, T343K, T333P, M205T, P220R, A174P, A217P, G257D, A218D, I204T, N258K, L104Q, Y183N, R66T, Q171L, D62G, T93I, D115Y, K80E, I172F, Y183H, T287I, N198Y, G212A, Q216E, Y284N, P220Q, N258Y, S207N, L59R, H214R, I159S, D62N, A253V, I261S, E52K, G197W, L244R, Q145P, A128D, P225L, T150P, E181A, F316C, L246R, S96F, V259L, G188R, Q69P, L59Q, L45I, L111R, H214L, M213T, D136G, F281I, P250T, A218T, Y176C, S318Y, R66M, T247A, V315A, L103P, P225Q, K210N, L179P, G162E, M56T, K331E, V315F, G283V, P250Q, A294G, R306I, L244Q, P220A, E98V, V323G, A174D, N258I, D41G, P158S, L301F, T287P, V339M, I67R, I204N, T190A, V337G, V286F, T49P, I172M, Y345H, N47I, L301V, M213V, I261T, L322Q, T190N, S321T, L74W, L341R, T264P, F300S, Y345F, I67K, S318F, L322I, G195A, L189R, I172S, V339L, M213L, H168N, T112A, L63V, E72G, P250S, I85S, W193L, G241V, D297E, V339E, W193C, E72V, G71V, T112P, I159T, R40G, A218G, E224V, L201V, E328G, S96Y, K80N, V311M, E72K, T343I, T190S, D312Y, I194T, T299K, M335V, L163R, D344Y, L63M, D165V, D297G, L341Q, G79E, A253G, A254G, L77V, L177V, L246Q, L201M, D136A, I172N, Y284C, T242S, T219N, P225S, A294V, G100V, K70I, Y284H, Q348P, F211S, H202D, D115G, T127P, D62H, I67T, T242A, L131S, K210Q, A217T, L349P, G188S, N199I, P225T, E252G, A237T, G257V, H202Y, V259I, E181D, T219A, T127R, G83D, L177I, A217S, P305R, Y55D, T93A, T287A, I160M, G79R, F316V, A295G, E72A, D136E, S192G, T178S, N161S, Y55C, S81Y, E328K, D313V, A102P, F281C, P352R, I157L, A295V, A294T, I157F, L95S, R94G, L177H, M335T, W58C, R306T, E181Q, T299I, S203A, P352L, F48V, L186V, I85T, R66K, E239G, T287K, D263N, T287R, T230N, E87A, T178A, R66W, L103F, P352H, M335I, L163Q, K80T, Q282P, P352A, T299R, Q285P, S90G, W58L, H202R, Q114K, V315L, F86S, L342V, K54I, Y317D, R306G, D165Y, S346P, V323M, G105E, A152V, T264I, K46I, E328V, L82F, M338T, N240K, F316I, S318A, D312G, D196Y, W298C, N248I, T49I, L189V, G79A, S192I, G283C, A152T, Q145E, M84T, F86V, A237G, A253S, A280G, G222C, T113P, P75R, S321A, L111H, D263E, A254V, M134K, T299A, F354S, T343A, F354V, D344A, L260F, R40H, L76F, W58R, W58G, P75H, D249A, R94I, G39R, R320G, G222S, A155G, H302N, E52A, P305A, T112S, A294S, Y317S, D249V, D165A, M288V, D313Y, D249Y, Y223S, M288I, D344H, P319L, I159M, P305S, W58S, Q285L, D344G, E309K, A254S, T290N, F101Y, Y223N, A295T, F48C, L260V, E314V, R306S, R40C, N258S, D226G, I116T, Y236N, G105R, K144I, A209G, K54N, K68I, F281S, T290S, A135E, F354C, K187I, Y167N, I172L, L301I, D62E, G39C, I170N, Y55S, L104V, L245W, N198H, P305T, F300I, Y236D, K70T, Q180R, P352T, E87D, E51V, Y55N, E98A, V337L, F300C, Y317C, R40L, Q279P, P75T, H302Q, N258T, F86I, P75A, A140G, A128P, S340F, A280P, D313G, M335L, A336S, E328Q, T219I, D313H, E51G, E122K, T99K, F316L, V311E, S132Y, K331T, D226Y, D136H, D312H, V339A, A233G, L111P, Q285E, F281Y, T99R, I261F, A61T, N258H, E310A, S132P, E87V, L42I, G106A, P75S, T290A, D313E, E98G, D165G, S203C, A174G, E252D, L57V, E326D, K80Q, F101S, D136N, F354L, A137T, Q285H, M205L, L148V, G39A, L118S, L179V, I334N, M288T, N258D, I200S, L186M, S156Y, Q171E, I53V, A61V, E314K, F300V, K292I, D313A, A291S, T219S, H107R, S203T, T49A, L232S, E310G, I116N, S132F, G283A, M288R, Y236H, E122V, V337A, D149G, I157M, N198I, L191V, K38E, R277W, H117D, H202Q, F65I, E72Q, R277G, L245S, I67L, S123I, D147G, L349R, E98Q, F281L, A102E, V259A, D249H, T112I, H214D, K88I, S146L, E310Q, G71A, M268R, A218S, E309V, L278P, A152G, L111V, N248K, Y167S, A295D, A135P, M288K, L76V, L148M, G241A, K68T, S346L, R306K, G39S, L95W, L251S, A102V, Y236S, N199T, E51K, Q180K, E328D, Y223C, L151V, H182R, D175Y, E309G, D313N, T44A, D312N, H107D, I116S, Y236C, S296Y, L37V, E310V, L251W, M338I, G197A, L42V, L103H, K68R, I170S, A135G, G241S, K68N, E273K, V138A, F86L, I261L, K54T, S146P, V323A, G50R, I261V, Y317H, L177F, S133I, E122A, D312V, V229A, W265R, R330K, K70E, G269V, A327G, E239V, A233S, L166W, E87Q, S156C, V293G, G71E, M338V, L151M, I67M, V130E, V293D, E52D, S132C, Q78H, Y317N, P108L, G241R, F86C, F65V, L166S, L103R, G257C, T247S, L349H, N240S, R89K, W265C, G105A, Q282L, E72D, N248Y, D226V, G256A, L104M, V286L, E310D, D312E, K46N, L77M, A280V, S60T, H202N, S296C, V293I, D126Y, N121I, F65L, K68E, G256R, E51Q, G188D, K331Q, V229L, G257S, L304M, V35E, K351N, G119V, T113K, S185A, K289M, D344E, L341M, I194M, G100S, L74M, A140S, P225A, L251V, A137G, L349F, G241C, Y223H, R277L, L95F, D196V, T113R, D312A, L173M, T287S, K243E, L74V, L139M, E314Q, D175V, L232W, A61S, I67V, L232F, K289T, S318C, A155V, S156A, F65S, T299S, T343S, Q78L, L95V, W265G, L43V, K221N, E273V, W265S, R129P, E122G, R94T, A208S, K243M, D196H, A237S, M206I, W265L, Q348L, E252A, R94S, K187T, S132A, C109W, I172T, F300L, Q114H, A291G, K88N, G241D, M84V, A128T, Y73C, K221T, M288L, L131W, A102G, Y73D, S340T, S185F, Q348H, A336G, K38M, E273A, E309A, K353I, D249E, D165N, E239A, Q36P, Q69R, A327T, L111I, V142E, K80R, M268K, L57I, A280S, D126H, Q216K, F316Y, T112N, N121Y, G256E, T333S, Q279H, L59I, D149A, E51A, N198D, D226H, E314D, E314A, Q235H, G50E, F65C, E273G, L166F, L118M, Q350H, L124R, K231N, L251F, K221M, Y55F, S90T, S81F, E309Q, D126G, N33I, Q270P, L278H, D147N, K38T, D147Y, G283D, S296T, F86Y, L37M, E252Q, L304S, Y317F, R129C, M84I, T93S, G269R, K80M, N248S, K276M, V293A, E154Q, E154K, L341V, A209S, G83S, E309D, V35G, K46T, S123G, Y55H, K34I, T91A, D126N, E326G, D196N, D226A, G162A, S184C, K243Q, I266K, V293F, E234G, M134I, K238T, E224G, A128S, K34E, G71R, C303G, T97S, C109Y, D126A, L131V, S267R, K276T, L232V, A128V, L278F, P319R, E272V, K34N, Q36L, T127K, D196G, L82V, E272K, N198K, E271V, N248T, S133R, K292T, Q348R, E239Q, P308R, I334F, L246M, D226E, N199S, L118V, K353R, Q235L, G119C, V337I, L245F, E154G, L76I, V35A, F48Y, R129G, S267T, K54R, L245M, H255L, N47Y, S267C, N47T, L131F, D147H, G119A, N33Y, Q69L, R320Q, V293L, A140T, K351T, N248D, H107Q, A327S, Q235R, D249N, L342M, K238N, K88T, Q114L, L244M, L278V, H255D, D147E, L163V, E272G, T99S, S228I, A295S, K144T, H117R, I157V, V130G, H214N, G269E, E272Q, I334L, Y73F, L43I, K187Q, E234A, I200L, A327E, K307E, K243N, K221E, H117P, R129L, E272A, P319T, Q279L, T125M, K46E, A227T, A155S, D41H, S207T, L349V, D196E, Y73S, E326V, D226N, R129S, K289R, K231T, L131M, A102T, S133N, P319A, I266R, S346A, I170V, R129H, L103I, A227D, E154D, H255Y, K276E, K274E, V35L, P308L, K144Q, Q282H, K238I, K221R, S184T, E234V, I334V, K276N, S81A, K307M, K331M, K231M, P308A, K38Q, Q36R, I266T, G269A, Y73N, S133C, T230A, S123C, E271Q, D196A, T127A, N240H, K70Q, V142L, I116F, L59V, K238E, K276Q, Y223F, K292N, H107N, K46Q, I160V, Q235K, T91N, A227S, K153N, L232M, K243T, Q180H, I334S, A174S, L95M, H117N, R94K, S228C, K46R, K274T, K274M, S156T, I200N, N198T, T113S, T49N, C303S, I170M, N33T, Q145H, E272D, L139V, K70R, L215I, K276R, T125P, Y167F, K231E, K70N, E252V, S185C, S123R, K275T, E271A, P319H, N47S, K153R, C109S, H255N, V35M, K275N, L278R, M268L, Q36H, K289N, I200T, I85L, V130A, K38R, T150I, I261M, F324C, G119D, Q36E, Q235E, N248H, K34R, A102S, N47H, S146T, L215V, V229I, M206V, K88E, K88R, L166M, V130I, S267N, L191L. 51. A method of screening for a protein variant that exhibits dominant negative interactions with a wildtype protein, the method comprising: a) providing a population of haploid yeast strains each expressing a protein variant of arrangements 42-43; b) mixing the population of haploid yeast strains expressing the protein variant with a haploid yeast strain expressing a WT protein to generate a population of diploid yeast strains each expressing a variant protein in combination with the WT protein; c) growing the diploid yeast strains on a minimal growth medium; d) screening the population of diploid yeast strains expressing a variant protein in combination with the WT protein for growth based on a growth score; and e) identifying a protein variant that exhibits dominant negative interactions with a wildtype protein based on the growth score that was screened for. 52. The method of arrangement 51, wherein the minimal growth medium lacks arginine. Example 1. Expression construct encoding protein variants of OTC [0284] The human OTC sequence can functionally replace the corresponding ARG3 gene in yeast. This single copy can be stably integrated into the genome under the control of the native yeast regulatory sequences for transcription, translation, and mRNA stability with the nucleic acid comprising the sequence. [0285] While the human OTC protein contains an N-terminal 32 amino acid leader sequence to direct import into the mitochondria, the yeast ARG3 ortholog is cytosolic. Therefore, amino acids 2-32 of the human OTC protein were omitted from the yeast expression construct. The OTC protein coding sequence without mitochondrial leader was then codon harmonized for expression in yeast, using a method designed to match the codon usage frequency of Saccharomyces cerevisiae as follows. Briefly, at amino acid positions conserved between the yeast and human sequences, the codon sequence for the yeast ortholog, ARG3, in the S288c reference sequence (R64.2.1 annotation in Saccharomyces Genome Database) was selected. In the non-conserved locations, codons for the appropriate OTC amino acid were chosen to be as similar as possible to the usage frequency of the codons at corresponding ARG3 codons. [0286] The truncated, codon harmonized protein coding sequence is referred to as yOTC (SEQ ID NO: 111) as depicted in Figure 9. [0287] For the amino acid substitution mutants, the sequences of SEQ ID NOS: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 as depicted in Figures 3-110 were used. [0288] For expression in yeast, the yOTC gene was placed under the control of the native yeast ARG3 promoter. Because ARG3 and its downstream gene TRL1 are in a tail-to- tail orientation and use the same 186 bp terminator sequence, introduction of the yOTC gene cassette via homologous recombination into the yeast genome could interfere with TRL1 gene expression. Therefore, the terminator sequence for TRL1 termination was maintained and a TRP2 terminator sequence was introduced upstream of the drug marker to control the termination of yOTC. OTC_codon_optimized integrating plasmid 1-6055= Cloning vector AB614_yOTC 1-1335= pUC19 sequence 344-1652= HO-L recombination-directing sequence derived from Saccharomyces cerevisiae 1656-2066= ARG3 promoter from S. cerevisiae 2067-3038= Homo sapiens ornithine transcarbamylase codon optimized for expression in S. cerevisiae 3039-3429= TRP2 terminator from S. cerevisiae 3440-3818= TEF promoter from A. gossypii 3819-4391= confers clonNAT resistance 4397-4594= TEF terminator from A. gossypii 4595-4679= Vector sequence from plasmid pFA6a-natMX6 4680-4715= HO-R recombination-directing sequence derived from S. cerevisiae 4722-6055= pUC19 sequence Example 2. Assay for identification of high functional and stable OTC protein variants [0289] Ornithine transcarbamylase activity is required for yeast to grow in the absence of exogenously supplied arginine. Colony growth on minimal medium lacking arginine is a quantitative measurement of enzyme function that is amenable to high throughput analysis. A library of all SNP-accessible amino acid substitution mutations across the length of the human OTC protein was introduced, with the exception of the first and last codons and the mitochondrial leader sequence, which was not included in the expression construct. Following integration into the yeast genome in single copy, the growth of yeast strains harboring each OTC variant was quantified at least three times on medium lacking arginine. The DNA sequences of the expression constructs present in each strain were determined and strains harboring expression constructs with secondary mutations (in addition to the intended amino acid substitution mutation) were removed from further consideration. The growth values represent the median values from at least one (and in most cases more than one) independently derived strain, each of which was assayed at least three times. The standard error reflects the error associated with these technical and biological replicates. [0290] Growth score was used as a measure of functional impact of the variants. The growth of 84% (1570 variants out of 1879) of the total possible SNP-accessible variants were quantitated. The growth values are plotted as points on a scatter plot ordered by their amino acid position as shown in Figure 10. Functional scores below 0.05 in the assay represent alleles with extremely low activity and thus strains showed little growth. Approximately 27% of variants displayed growth values in this range of the assay. Approximately 62% of variants fell in the range between 0.05 and the value of the wildtype protein (1.0). The remaining 11% of variants exhibited growth values greater than that conferred by the wildtype protein. [0291] The results of the assay are depicted as median normalized growth value and are shown in Table 1. The protein variants that exhibited a growth score of 1.05 or greater than the wild-type that are listed in Table 2 and the protein variants that exhibited a growth score of 0.95 or lower than the wild-type are listed in Table 3.

TABLE 1 TABLE 2 TABLE 3 Example 3. Assay for identification of dominant negative OTC variants [0292] To test whether any of the OTC variants exhibit dominant negative interactions, growth of haploid yeast strains harboring haploid OTC variants R92P, S90G, S90R, H117R, A137T, R141Q, H168R, H168P, P169S, Q171R and D263H and heterozygous yeast diploids (yOTC variant/wild type yOTC) were tested in the absence of arginine using the method as mentioned in example 2. Growth on minimal medium is calculated as the product of the area and the intensity from plates imaged after 3 days. Growth estimates for each genotype are displayed relative to wild type yOTC (set to 1.0) and arg3 deletion mutant (set to 0). Dominant negative activity would lead to lower growth of the heterozygous diploid versus the arg3/yOTC wild type diploid. Functional score around 0.8 in the assay represent that there was no dominant negative activity of the variant. As depicted in Figure 11, for most variants assayed, the functional score of the heterozygous diploid yeast strain containing one copy of the OTC variant listed and one copy of wildtype OTC was approximately 0.8. Variants R92P and S90G exhibited a functional score of less than 0.8 indicating these mutants are potential dominant negative variants. [0293] This assay will be expanded to test whether any variants in the OTC protein coding sequence exhibit dominant negative interactions with the wildtype OTC protein. Such variants could include individual amino acid substitutions, multiple amino acid substitutions, frameshift mutations, early termination codons, and in frame deletions of one or more amino acids. Example 4. Method of diagnosis and treatment of OTC deficiency in a subject [0294] A subject is identified as potentially having a genetic disorder related to OTC deficiency. The functional status of OTC in the subject is determined. If the subject exhibits at least one mutation that results in a protein variant of reduced activity and/or stability in OTC as listed in Table 3 or if the subject harbors at least one mutation that encodes a dominant negative protein variant, the subject is diagnosed as having OTC deficiency. A composition comprising a therapeutic amount of one or more mutants that result in one or more protein variants of increased activity and/or stability listed in Table 2 is administered to the subject via gene therapy. The subject is continuously monitored for reduction of symptoms associated with OTC deficiency and the treatment is continued until there is an increase in the function of OTC and the occurrence and/or symptoms of the disorder are reduced, alleviated, or limited. [0295] As used herein, the section headings are for organizational purposes only and are not to be construed as limiting the described subject matter in any way. All literature and similar materials cited in this application, including but not limited to, patents, patent applications, articles, books, treatises, and internet web pages are expressly incorporated by reference in their entirety for any purpose, including the disclosures specifically referenced herein. When definitions of terms in incorporated references appear to differ from the definitions provided in the present teachings, the definition provided in the present teachings shall control. It will be appreciated that there is an implied “about” prior to the temperatures, concentrations, times, etc. discussed in the present teachings, such that slight and insubstantial deviations are within the scope of the present teachings herein. [0296] It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles "a" or "an" limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases "one or more" or "at least one" and indefinite articles such as "a" or "an" (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of "two recitations," without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g.,“ a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g.,“ a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B. [0297] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group. [0298] Any of the features of an embodiment of the first through eleventh aspects is applicable to all aspects and embodiments identified herein. Moreover, any of the features of an embodiment of the first through eleventh aspects is independently combinable, partly or wholly with other embodiments described herein in any way, e.g., one, two, or three or more embodiments may be combinable in whole or in part. Further, any of the features of an embodiment of the first through eleventh aspects may be made optional to other aspects or embodiments.