Dominant Gα mutations in human disease: unifying mechanisms and treatment strategies.

ABSTRACT: Sixteen Gα-subunits transduce hundreds of G protein-coupled receptors and control countless cellular activities. Mutations in respective GNA genes underlie developmental, oncological, metabolic, neurological, and other pathologies. In addition to classical loss-of-function (LOF) and gain-of-function (GOF) mutations (the former represented by gene deletions/truncations, the latter by specific GTP hydrolysis-deficient mutations), multiple pathogenic dominant missense variants have been discovered in GNA genes, and their numbers constantly increase through advanced genetic diagnostics. While these mutations often have confusing features of hypomorphic, dominant-negative, and GOF mutations, many of the pathogenic Gαo (and by inference, other Gα-subunit) variants have recently emerged as neomor

SUBMITTER: Katanaev VL 

PROVIDER: S-EPMC12423288 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature