GNAQ

GNAQ is a human gene encoding the guanine nucleotide-binding protein G(q) subunit alpha, a member of the G protein alpha subunit family involved in signal transduction. G alpha q proteins relay signals from a diverse set of G protein-coupled receptors to phospholipase C beta (PLCβ). Upon GPCR activation, the GNAQ-encoded protein exchanges GDP for GTP, dissociates from the G beta gamma dimer, and activates PLCβ, leading to hydrolysis of PIP2 into IP3 and DAG, mobilization of intracellular Ca2+, and activation of protein kinase C and downstream signaling cascades.

The GNAQ protein belongs to the G alpha q family, which also includes GNA11. It is associated with the inner surface of the plasma membrane, a localization supported by N-terminal lipid modifications that anchor the protein to the membrane. The gene is located on chromosome 9q21.2 and is widely expressed in human tissues.

Mutations in GNAQ can have clinical consequences. Activating somatic mutations at residues 183 and 209—most notably R183Q in vascular malformations such as Sturge-Weber syndrome, and Q209L/R in uveal melanoma and blue nevi—drive constitutive signaling through PLCβ and PKC, contributing to tumorigenesis in affected cells. GNAQ and its paralog GNA11 are among the most commonly mutated G alpha subunits in uveal melanoma, with shared activation of downstream pathways including PKC and MAPK signaling.