Mapping structural distribution and gating-property impacts of disease-associated mutations in voltage-gated sodium channels.

ABSTRACT: Thousands of voltage-gated sodium (Na_v) channel variants contribute to a variety of disorders, including epilepsy, cardiac arrhythmia, and pain disorders. Yet, the effects of more variants remain unclear. The conventional gain-of-function (GoF) or loss-of-function (LoF) classifications are frequently employed to interpret mutations' effects and guide therapy for sodium channelopathies. Our study challenges this binary classification by analyzing 525 mutations associated with 34 diseases across 366 electrophysiology studies, revealing that diseases with similar GoF/LoF effects can stem from unique molecular mechanisms. Utilizing UniProt data, we mapped over 2,400 disease-associated missense mutations across Na_v channels. This analysis pinpoints key mutation hotspots an

SUBMITTER: Akbari Ahangar A 

PROVIDER: S-EPMC11404175 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature