Guanine nucleotide-binding protein subunit alpha-14 (GNA14) (GNA14)

Guanine nucleotide-binding protein subunit alpha-14 (GNA14) is a member of the Gq family of heterotrimeric G protein alpha subunits that functions as a critical transducer in G protein-coupled receptor (GPCR) signaling pathways. Upon activation by a receptor, GNA14 stimulates phospholipase C-beta, which in turn triggers the release of intracellular calcium and the activation of protein kinase C (UniProt: P30677). While it shares structural similarities with other Gq family members, GNA14 exhibits a distinct expression pattern and is particularly relevant in vascular biology. Somatic gain-of-function mutations in GNA14, most notably the Q205L variant, have been identified as key drivers in the pathogenesis of various vascular tumors and malformations, such as tufted angioma and kaposiform hemangioendothelioma (PubMed: 26757174). These mutations lead to constitutive signaling through the MAPK/ERK pathway, promoting uncontrolled cell growth and survival. Although there are currently no FDA-approved therapies specifically targeting GNA14, research is ongoing into the use of Gq-family inhibitors like FR900359 to treat GNA14-mutated conditions (PubMed: 30104373).

Other names

G alpha 14G-alpha-14GNA14Guanine nucleotide-binding protein alpha 14 subunit

Inhibition of the GDP-GTP exchange on the G alpha subunit, preventing downstream activation of phospholipase C and calcium mobilization (PubMed: 30104373).