Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) and Guanine nucleotide-binding protein G(11) subunit alpha (GNA11) (GNAQ/GNA11)

GNAQ and GNA11 are closely related members of the Gq family of heterotrimeric G protein alpha subunits, responsible for coupling G protein-coupled receptors (GPCRs) to the phospholipase C beta (PLCβ) signaling pathway (UniProt P50148, P29992). Upon activation, these proteins stimulate the production of second messengers like inositol trisphosphate (IP3) and diacylglycerol (DAG), leading to intracellular calcium release and activation of protein kinase C (PKC) (PubMed: 29309011). Somatic gain-of-function mutations in GNAQ or GNA11, most commonly at the Q209 or R183 positions, are the primary oncogenic drivers in approximately 90% of uveal melanomas and are also associated with Sturge-Weber syndrome and port-wine stains (NIH: PMC6548593, PubMed: 23654366). These mutations lock the proteins in a constitutively active, GTP-bound state, driving uncontrolled cell proliferation through the MAPK and YAP pathways. Therapeutic strategies focus on direct inhibition of the G-alpha subunits or targeting downstream effectors like PKC and MEK, with several agents currently in clinical development for GNAQ/11-mutant cancers (PubMed: 30635424).

Other names

G-alpha-qG-alpha-11GAQG11Gq/11GNAQGNA11

Direct inhibition of the G-alpha subunit GTPase activity or inhibition of downstream effectors such as Protein Kinase C (PKC) and the Mitogen-Activated Protein Kinase (MAPK) pathway (PubMed: 30635424, 29309011).