Atomic-level investigation of KCNJ2 mutations associated with ventricular arrhythmic syndrome phenotypes.

ABSTRACT: KCNJ2 encodes the inward rectifying potassium channel (Kir2.1) that underlies I_K1 which maintains the cardiac resting membrane potential and regulates excitability. Mutations in KCNJ2 have been linked to several clinical phenotypes associated with life-threatening ventricular arrhythmia and sudden death including Andersen-Tawil syndrome (ATS) from loss of function mutations, and Short QT Syndrome 3 from gain of function mutations. Detailed structural-functional relationships to explain the arrhythmia phenotypes are understudied and limit the capacity to provide precision medicine. Here, we combine in-depth and complementary computational molecular modeling techniques with functional analysis from three patients with ATS that harbor KCNJ2 mutations R67Q, R218L, and G300D. Whole-c

SUBMITTER: Munawar S 

PROVIDER: S-EPMC11965533 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature