Dysfunction of ATP7B Splicing Variant Caused by Enhanced Interaction With COMMD1 in Wilson Disease.

ABSTRACT:

Background & aims

The association between Wilson disease and various ATP7B mutations is well-established; however, the molecular mechanism underlying the functional consequence of these mutations, particularly the splicing mutations, remains unclear. This study focused on the ATP7B c.1543+1G>C variant, to reveal a universal pathogenic mechanism of the ATP7B mutants with altered N-terminus.

Methods

The splicing assay and RNA pull-down were performed to explore the mechanism of the aberrant splicing. The ATP7B knockout HuH-7 cell line and Atp7b^-/- mice were created, and the functional consequence of the mutant ATP7B were evaluated in vitro and in vivo.

Results

The c.1543+1G>C mutation resulted in the skipping of ATP7B exon 3, and the mutant ATP7B showed a los

SUBMITTER: Zhou D 

PROVIDER: S-EPMC11629249 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature