The GNAQ gene is composed of 7 exons spanning a region of 310993 nucleotides.

Transcript length is 6539 bp. Length of ORF is 1080 bp.

GNAQP in 2q14.3-q21.

Amino acid residues: 359. Molecular weight: 42141 daltons.
GNAQ is a proto oncogene which encodes for alpha subunit of q class of heterotrimeric GTP binding protein.

GNAQ is ubiquitously expressed in all tissues.

Cytoplasm. Signaling occurs at the membrane.

GNAQ mediates signal between the G protein coupled receptor (GPCR) and downstream effectors. Receptor activation by ligand binding causes the activation of GNAQ by catalyzing the release of GDP and binding of GTP. In its active form GTP-bound GNAQ causes the release of the beta and gamma subunits of the heterotrimeric G-protein. GTP-GNAQ and beta and gamma subunits transfer the receptor-mediated signal to downstream effectors through secondary messengers which participate in diverse signaling pathways to evoke different effectors. The known effectors for GNAQ include PLC beta, p63-RhoGEF, Trio, and Duet (Maize et al., 2005; Eom et al., 2009). GNAQ has been shown to activate the MAP kinase pathway, possibly via DAG-mediated activation of protein kinase C isoforms. GNAQ has an intrinsic GTPase domain at the C terminus which causes the hydrolysis of GTP to GDP and the G-alpha-GDP re-associates with G-beta and G-gamma subunits.

GNAQ is one of the four members belonging to the Gq-alpha family. Compared to GNAQ the other three members G11alpha, G14alpha, G16 alpha have 90%, 80%, and 57% amino acid sequence homology, respectively (Eom et al., 2009).

Somatic mutations of GNAQ affect codons 183 and 209 resulting in R183Q, Q209L, Q209P, Q209R, and Q209Y.

No germinal mutations have been described.

Somatic mutations in GNAQ have been described in melanocytic neoplasia (Hubbard et al., 2006; Onken et al., 2008; Küsters-Vandevelde et al., 2009). In Uveal Melanoma, 97% of the hotspot mutations cause the amino acid substitution Q209L, the other 3% of mutations cause amino acid change to R183Q. The Glutamine 209 of GNAQ is similar to residue 61 of RAS protein. The Q209 and R183 mutations cause complete or partial loss of intrinsic GTPase activity respectively thereby locking the protein in a constitutively active form. Q209 and R183 mutations occur in a mutually exclusive pattern in human neoplasia. Mutations in GNAQ are also mutually exclusive from the hotspot mutations in GNA11, which belongs to the same family and shares 90% sequence homology. GNAQ mutations are not concomitant with other common oncogenic mutations in BRAF, NRAS or KIT found in melanocytic neoplasia.

Categories	Subtypes	GNA11 Ex5		GNAQ Ex5		Neither		Total
		number of samples	%	number of samples	%	number of samples	%
Blue nevi	Amelanotic blue nevus	0	0.0%	7	70.0%	3	30.0%	10
	Cellular blue nevus	3	8.3%	26	72.2%	7	19.4%	36
	Common blue nevus	4	6.7%	39	65.0%	17	28.3%	60
	Nevus of Ito	0	0.0%	0	0.0%	7	100.0%	7
	Nevus of Ota	1	5.0%	2	10.0%	17	85.0%	20
	Malignant blue nevus	1	16.7%	2	33.3%	3	50.0%	6
Total		9	6.5%	76	54.7%	54	38.8%	139
Ocular melanocytic tumors	Conjunctival melanoma	0	0.0%	0	0.0%	9	100.0%	9
	Uveal melanoma, primary	52	31.9%	73	44.8%	38	23.3%	163
	Uveal melanoma, metastasis	13	56.5%	5	21.7%	5	21.7%	23
	Uveal nevus	0	0.0%	1	100.0%	0	0.0%	1
Total		65	33.2%	79	40.3%	52	26.5%	196
Other nevi	Common nevus	0	0.0%	0	0.0%	22	100.0%	22
	Congenital nevus	0	0.0%	0	0.0%	17	100.0%	17
	Deep penetrating nevus	0	0.0%	0	0.0%	27	100.0%	27
	Spitz nevus	0	0.0%	0	0.0%	19	100.0%	19
	Atypical Spitz tumor	0	0.0%	0	0.0%	20	100.0%	20
Total		0	0.0%	0	0.0%	105	100.0%	105
Extra-ocular melanomas	Acral	0	0.0%	0	0.0%	47	100.0%	47
	CSD	0	0.0%	1	1.4%	73	98.6%	74
	Mucosal	0	0.0%	0	0.0%	62	100.0%	62
	NonCSD	0	0.0%	0	0.0%	90	100.0%	90
Total		0	0.0%	1	0.4%	272	99.6%	273
Grand Total								713

Table representing the exon 5 mutation frequencies of GNAQ and GNA11 in melanocytic neoplams.