GNAQ

protein-coding

G protein subunit alpha q, the group of G protein subunits alpha, group q

Gene summary

This locus encodes a guanine nucleotide-binding protein. The encoded protein, an alpha subunit in the Gq class, couples a seven-transmembrane domain receptor to activation of phospolipase C-beta. Mutations at this locus have been associated with problems in platelet activation and aggregation. A related pseudogene exists on chromosome 2.[provided by RefSeq, Nov 2010]

MANE transcript

NM_002072.5

Inheritance

ClinVar variants

P:9U:25B:17

Top phenotype

Sturge-Weber syndrome

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr9:77,716,097-78,031,811

External References & Databases

Ensembl (ENSG00000156052)

Transcript & Mutation Effects

hg38 • Region Span ~315.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Sturge-Weber syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008501

Submitter: Ambry Genetics

Sturge-Weber syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008501

Submitter: G2P

congenital hemangiomaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0018715

Submitter: G2P

Sturge-Weber syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008501

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GNAQ variants in ClinVar

12 Conditions Cataloged

not providedTotal: 22

Inborn genetic diseasesTotal: 14

not specifiedTotal: 10

GNAQ-related disorderTotal: 6

Sturge-Weber syndromeTotal: 5

Familial multiple nevi flammeiTotal: 5

Segmental undergrowth associated with capillary malformationTotal: 2

HemangiomatosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002072.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	14 clinvar	2 clinvar	17
missense	6 clinvar	3 clinvar	20 clinvar	1 clinvar		30
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	6	3	25	15	2	51

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002072.5	RefSeq	NP_002063.2	7	MANE Select
ENST00000286548.9	Ensembl	ENSP00000286548.4	7	MANE Select
ENST00000411677.1	Ensembl	ENSP00000391501.1	4	Standard
ENST00000857199.1	Ensembl	ENSP00000527258.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Platelet activation - Homo sapiens (human)
Cortisol synthesis and secretion - Homo sapiens (human)
Aldosterone synthesis and secretion - Homo sapiens (human)
Oxytocin signaling pathway - Homo sapiens (human)

Biological Process

action potential
negative regulation of protein kinase activity
G protein-coupled receptor signaling pathway
adenylate cyclase-modulating G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway

Molecular Function

G protein-coupled receptor binding
GTPase activity
GTPase activator activity
protein binding
GTP binding

Cellular Component

photoreceptor outer segment
cytoplasm
lysosomal membrane
heterotrimeric G-protein complex
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000286548
Coding exons: 7
Length: 315372
Individuals with no LoFs: 125411
Homozygous LoFs: 0
Heterozygous LoFs: 223
Defined: 125634
p: 0.000888

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.66	56	202	0.277	0.0000107	2375
Missense (PolyPhen)		7	80.838	0.086592		966
Synonymous	0.444	75	80.1	0.937	0.00000471	661
Loss of Function	3.83	2	20.9	0.0958	0.00000137	216

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.0030	0.0027	notable
East Asian	0.0021	0.0020	notable
Finnish	0.0013	0.0012	notable
European (Non-Finnish)	0.00062	0.00060	rare
South Asian	0.00081	0.00075	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro) (By similarity). {ECO:0000250}.;
Disease: DISEASE: Capillary malformations, congenital (CMC) [MIM:163000]: A form of vascular malformations that are present from birth, tend to grow with the individual, do not regress spontaneously, and show normal rates of endothelial cell turnover. Capillary malformations are distinct from capillary hemangiomas, which are highly proliferative lesions that appear shortly after birth and show rapid growth, slow involution, and endothelial hypercellularity. {ECO:0000269|PubMed:23656586}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Sturge-Weber syndrome (SWS) [MIM:185300]: A syndrome characterized by an intracranial vascular anomaly, leptomeningeal angiomatosis, most often involving the occipital and posterior parietal lobes. The most common features are facial cutaneous vascular malformations (port-wine stains), seizures, and glaucoma. Stasis results in ischemia underlying the leptomeningeal angiomatosis, leading to calcification and laminar cortical necrosis. The clinical course is highly variable and some children experience intractable seizures, mental retardation, and recurrent stroke-like episodes. {ECO:0000269|PubMed:23656586}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.440

Intolerance Scores

LoFtool: 0.0946
RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.512

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium