Pathogenicity Prediction of GABA_A Receptor Missense Variants.

ABSTRACT: Variants in the genes encoding the subunits of gamma-aminobutyric acid type A (GABA_A) receptors are associated with epilepsy. To date, over 1000 clinical variants have been identified in these genes. However, the majority of these variants lack functional studies and their clinical significance is uncertain although accumulating evidence indicates that proteostasis deficiency is the major disease-causing mechanism for GABA_A receptor variants. Here, we apply two state-of-the-art modeling tools, namely AlphaMissense, which uses an artificial intelligence-based approach based on AlphaFold structures, and Rhapsody, which integrates sequence evolution and known structure-based data, to predict the pathogenicity of saturating missense variants in genes that encode the major

SUBMITTER: Wang YJ 

PROVIDER: S-EPMC10680766 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature