Analysis of Wilson disease mutations revealed that interactions between different ATP7B mutants modify their properties.

ABSTRACT: Wilson disease (WD) is an autosomal-recessive disorder caused by mutations in the copper (Cu)-transporter ATP7B. Thus far, studies of WD mutations have been limited to analysis of ATP7B mutants in the homozygous states. However, the majority of WD patients are compound-heterozygous, and how different mutations on two alleles impact ATP7B properties is unclear. We characterized five mutations identified in Indian WD patients, first by expressing each alone and then by co-expressing two mutants with dissimilar properties. Mutations located in the regulatory domains of ATP7B-A595T, S1362A, and S1426I-do not affect ATP7B targeting to the trans-Golgi network (TGN) but reduce its Cu-transport activity. The S1362A mutation also inhibits Cu-dependent trafficking from the TGN. The G1061E and G1101R

SUBMITTER: Roy S 

PROVIDER: S-EPMC7418023 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature