Guanine nucleotide binding protein (G protein), q polypeptide
359 amino acids; about 42 kDa
The GNAQ gene encodes a heterotrimeric GTP-binding protein α-subunit that couples G-protein coupled receptor signaling to the MAP kinase pathway. GNAQ codon 209 mutations form an alternative route to MAP kinase activation. GNAQ is important in melanocyte homeostasis and survival of melanocytes early in neural crest development.
Frequent somatic mutations have recently been identified in the ras-like domain of the heterotrimeric G protein alpha-subunit (GNAQ) in blue naevi 83%, malignant blue naevi (50%) and ocular melanoma of the uvea (46%). The mutations exclusively affect codon 209, prevent hydrolysis of GTP and turns GNAQ into its active, GTP-bound state.GNAQ constitutive activation results. Thus, GNAQ acts as a dominant oncogene.
Somatic mutations in the GNAQ gene at codon 209 are a frequent event in primary melanocytic neoplasms of the CNS.
More than 99% of somatic mutations in the GNAQ gene are substitutions missense.
Note: a GNAQ-related gene, GNA11, is also frequently mutated in uveal melanoma (Van Raamsdonk CD et al. 2010)
References (open access)
Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, Simpson EM, Barsh GS, Bastian BC. Nature. 2009 Jan 29;457(7229):599-602.
Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system. Küsters-Vandevelde HV, Klaasen A, Küsters B, Groenen PJ, van Engen-van Grunsven IA, van Dijk MR, Reifenberger G, Wesseling P, Blokx WA. Acta Neuropathol. 2010 March; 119(3): 317–323.
Mutations in GNA11 in uveal melanoma. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC. N Engl J Med. 2010 Dec 2;363(23):2191-9.