title: Quantitative relationship between mutated amino-acid sequence of human copper-transporting ATPases and their related diseases.
abstract: Copper-transporting ATPase 1 and 2 (ATP7A and ATP7B) are two highly homologous P-type copper ATPase exporters. Mutations in ATP7A can lead to Menkes disease which is an X-linked disorder of copper deficiency. Mutations in ATP7B can cause Wilson disease which is an autosomal recessive disorder of copper toxicity. In this study, we attempt to build a quantitative relationship between mutated ATPase and Menkes/Wilson disease. First, we use the amino-acid distribution probability as a measure to quantify the difference in ATPase before and after mutation. Second, we use the cross-impact analysis to define the quantitative relationship between mutant ATPase protein and Menkes/Wilson disease, and compute various probabilities. Finally, we use the Bayesian equation to determine the probability that Menkes/Wilson disease is diagnosed under a mutation. The results show (i) the vast majority of mutations lead to the amino-acid distribution probability increase in mutant ATP7As and decrease in ATP7Bs, and (ii) the probability that a mutation causes Menkes/Wilson disease is about nine tenth. Thus we provide a way to use the descriptively probabilistic method to couple the mutation with its clinical outcome after quantifying mutations in proteins.
authors.affiliation: Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi, 530007, China.
authors.forename: Shaomin
authors.initials: S
authors.lastname: Yan
authors.forename: Guang
authors.initials: G
authors.lastname: Wu
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics*; D000595:Amino Acid Sequence; D000596:Amino Acids; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics*; D050505:Mutant Proteins / Q000737:chemistry; D009154:Mutation / Q000235:genetics*
chemical_list: D000596:Amino Acids; D027682:Cation Transport Proteins; D050505:Mutant Proteins; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases