GNAQ

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

Basic information

Region (hg38): 9:77716096-78031811

Links

ENSG00000156052 ∙ NCBI:2776 ∙ OMIM:600998 ∙ HGNC:4390 ∙ Uniprot:P50148 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Sturge-Weber syndrome (Strong), mode of inheritance: AD
• Sturge-Weber syndrome (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNAQ gene.

• not provided (35 variants)
• Inborn genetic diseases (4 variants)
• not specified (3 variants)
• Sturge-Weber syndrome (3 variants)
• Familial multiple nevi flammei (3 variants)
• Melanoma (2 variants)
• Segmental undergrowth associated with capillary malformation (2 variants)
• Angioosteohypertrophic syndrome (1 variants)
• Abnormal cardiovascular system morphology (1 variants)
• Capillary malformation (1 variants)
• Hemangiomatosis (1 variants)
• Capillary malformation;Sturge-Weber syndrome (1 variants)
• GNAQ-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNAQ gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	2	10
missense	4	2	5	1		12
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				2	3	5
non coding			1	1	11	13
Total	4	2	8	10	13

Variants in GNAQ

This is a list of pathogenic ClinVar variants found in the GNAQ region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-77721374-G-A			Likely benign (May 16, 2021)
9-77721386-A-G			Likely benign (Jul 07, 2023)
9-77721506-C-G		Inborn genetic diseases	Uncertain significance (May 18, 2022)
9-77721518-C-T			Likely benign (Dec 31, 2019)
9-77728541-G-T		Inborn genetic diseases	Uncertain significance (May 25, 2022)
9-77728638-A-G			Likely benign (Oct 27, 2023)
9-77728669-T-TG		GNAQ-related disorder	Likely benign (Apr 05, 2019)
9-77728671-GA-G		not specified	Benign (May 04, 2021)
9-77728671-GAA-G		GNAQ-related disorder	Likely benign (Oct 28, 2019)
9-77728671-G-GA		not specified	Benign (May 04, 2021)
9-77728672-A-G		GNAQ-related disorder	Likely benign (Apr 05, 2019)
9-77728671-G-GAA		not specified	Benign (Jul 24, 2017)
9-77794222-C-G			Benign (Nov 12, 2018)
9-77794429-A-G			Benign (May 12, 2021)
9-77794433-T-C			Uncertain significance (Feb 25, 2021)
9-77794462-C-A			Uncertain significance (May 20, 2019)
9-77794493-A-G			Likely benign (Feb 13, 2018)
9-77794571-T-A		Familial multiple nevi flammei	Pathogenic (Jan 31, 2022)
9-77794571-T-G		Familial multiple nevi flammei	Pathogenic (Sep 11, 2021)
9-77794572-T-A		Melanoma • Uveal melanoma	Pathogenic/Likely pathogenic (Jul 14, 2015)
9-77794572-T-C		Melanoma • Abnormal cardiovascular system morphology • Sturge-Weber syndrome	Pathogenic (Nov 03, 2023)
9-77794572-T-G		Melanoma • Uveal melanoma	Pathogenic/Likely pathogenic (Jul 14, 2015)
9-77794572-TG-AA		Uveal melanoma	Likely pathogenic (Jul 14, 2015)
9-77794896-G-A			Benign (Nov 12, 2018)
9-77797577-C-A		Segmental undergrowth associated with capillary malformation	Pathogenic (Apr 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNAQ	protein_coding	protein_coding	ENST00000286548	7	315372

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.981	0.0193	125411	0	223	125634	0.000888

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.66	56	202	0.277	0.0000107	2375
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00109	0.00109
Ashkenazi Jewish	0.00297	0.00268
East Asian	0.00207	0.00201
Finnish	0.00126	0.00120
European (Non-Finnish)	0.000615	0.000599
Middle Eastern	0.00207	0.00201
South Asian	0.000812	0.000752
Other	0.00119	0.00114

dbNSFP

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.
• Pathway: 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);Long-term potentiation - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Glutamatergic synapse - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Long-term depression - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Gap junction - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Renin secretion - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Regulation of Microtubule Cytoskeleton;Alzheimers Disease;Corticotropin-releasing hormone signaling pathway;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;Circadian rythm related genes;Cell-type Dependent Selectivity of CCK2R Signaling;Calcium Regulation in the Cardiac Cell;Serotonin Receptor 2 and ELK-SRF-GATA4 signaling;Serotonin Receptor 2 and STAT3 Signaling;Signaling by GPCR;Signal Transduction;pertussis toxin-insensitive ccr5 signaling in macrophage;g-protein signaling through tubby proteins;links between pyk2 and map kinases;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;cxcr4 signaling pathway;ccr3 signaling in eosinophils;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;effects of calcineurin in keratinocyte differentiation;signaling pathway from g-protein families;thrombin signaling and protease-activated receptors;Thromboxane signalling through TP receptor;GPCR GroupI metabotropic glutamate receptor;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;Metabolism;Ghrelin;Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion;Acetylcholine regulates insulin secretion;Free fatty acids regulate insulin secretion;Regulation of insulin secretion;Signal amplification;Thrombin signalling through proteinase activated receptors (PARs);actions of nitric oxide in the heart;GPCR signaling-G alpha s Epac and ERK;activation of pkc through g-protein coupled receptors;Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;ADP signalling through P2Y purinoceptor 1;Hemostasis;Thromboxane A2 receptor signaling;Leptin;TSH;Integration of energy metabolism;G alpha (q) signalling events;GPCR downstream signalling;PAR4-mediated thrombin signaling events;PAR1-mediated thrombin signaling events;LPA receptor mediated events;S1P3 pathway;Arf6 signaling events;Plasma membrane estrogen receptor signaling;Sphingosine 1-phosphate (S1P) pathway;Endothelins;S1P2 pathway (Consensus)

Recessive Scores

• pRec: 0.440

Intolerance Scores

• loftool: 0.0946
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• pHI: 0.498
• hipred: Y
• hipred_score: 0.825
• ghis: 0.617

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.512

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gnaq
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; pigmentation phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype

Gene ontology

• 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;activation of phospholipase C activity;G protein-coupled acetylcholine receptor signaling pathway;glutamate receptor signaling pathway;blood coagulation;phototransduction, visible light;entrainment of circadian clock;platelet activation;positive regulation of GTPase activity;protein stabilization;regulation of canonical Wnt signaling pathway
• Cellular component: photoreceptor outer segment;cytoplasm;lysosomal membrane;heterotrimeric G-protein complex;plasma membrane;nuclear membrane;extracellular exosome
• Molecular function: G protein-coupled receptor binding;GTPase activity;GTPase activator activity;protein binding;GTP binding;G-protein beta/gamma-subunit complex binding;type 2A serotonin receptor binding;metal ion binding