GNAQ

Summary

GNAQ (G protein subunit alpha q, HGNC:4390) is a protein-coding gene on chromosome 9q21.2, encoding Guanine nucleotide-binding protein G(q) subunit alpha (P50148). Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. In precision oncology, GNAQ Mutation confers sensitivity to Trametinib in Uveal Melanoma (CIViC Level B); 7 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 13.4% of cell lines).

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.

Source: NCBI Gene 2776 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Sturge-Weber syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 69 total — 6 pathogenic
• Phenotypes (HPO): 85
• Druggable target: yes
• Precision-oncology evidence (CIViC): 8 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• Cancer dependency (DepMap): dependent in 13.4% of screened cell lines
• MANE Select transcript: NM_002072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4390
Approved symbol	GNAQ
Name	G protein subunit alpha q
Location	9q21.2
Locus type	gene with protein product
Status	Approved
Aliases	G-ALPHA-q, GAQ
Ensembl gene	ENSG00000156052
Ensembl biotype	protein_coding
OMIM	600998
Entrez	2776

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000286548, ENST00000411677, ENST00000857199, ENST00000915940

RefSeq mRNA: 1 — MANE Select: NM_002072 NM_002072

CCDS: CCDS6658

Canonical transcript exons

ENST00000286548 — 7 exons

Exon	Start	End
ENSE00001274232	77716097	77721513
ENSE00001274239	78031100	78031811
ENSE00001746610	77728514	77728667
ENSE00001773857	77922161	77922345
ENSE00003498186	77797520	77797648
ENSE00003536290	77815616	77815770
ENSE00003668412	77794463	77794592

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4412 / max 178.4977, expressed in 1723 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101093	4.7143	1492
101092	3.6870	1469
101094	0.0400	27

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	99.31	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.07	gold quality
postcentral gyrus	UBERON:0002581	99.04	gold quality
parietal lobe	UBERON:0001872	98.92	gold quality
inferior olivary complex	UBERON:0002127	98.91	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.78	gold quality
medulla oblongata	UBERON:0001896	98.68	gold quality
entorhinal cortex	UBERON:0002728	98.67	gold quality
orbitofrontal cortex	UBERON:0004167	98.65	gold quality
substantia nigra pars compacta	UBERON:0001965	98.56	gold quality
subthalamic nucleus	UBERON:0001906	98.55	gold quality
lateral globus pallidus	UBERON:0002476	98.48	gold quality
superior vestibular nucleus	UBERON:0007227	98.48	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.45	gold quality
cauda epididymis	UBERON:0004360	98.38	gold quality
cardia of stomach	UBERON:0001162	98.35	gold quality
inferior vagus X ganglion	UBERON:0005363	98.34	gold quality
superior frontal gyrus	UBERON:0002661	98.31	gold quality
lower lobe of lung	UBERON:0008949	98.31	gold quality
mammary duct	UBERON:0001765	98.30	gold quality
trigeminal ganglion	UBERON:0001675	98.27	gold quality
ventral tegmental area	UBERON:0002691	98.19	gold quality
trabecular bone tissue	UBERON:0002483	98.05	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.97	gold quality
caput epididymis	UBERON:0004358	97.97	gold quality
dorsal root ganglion	UBERON:0000044	97.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.88	gold quality
pons	UBERON:0000988	97.87	gold quality
pylorus	UBERON:0001166	97.85	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	30.33
E-CURD-119	yes	24.79
E-ANND-3	yes	17.24
E-CURD-10	no	620.32
E-MTAB-6386	no	101.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, PITX2, TP53

miRNA regulators (miRDB)

357 targeting GNAQ, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• The increase in Gqalpha and Gialpha1/2 expression was accompanied by an increase in Ca2+ signaling triggered by thrombin and other agonists known to signal to Ca2+ via these G-proteins in platelets. (PMID:11686331)
• A hemorrhagic diathesis patient has a defect in Galphaq gene expression in platelets but not neutrophils, possibly due to defects in transcriptional regulation or mRNA stability, and suggest a hematopoietic-lineage specific defect. (PMID:11848441)
• existence of a novel molecular mechanism by which Galpha(q) and the large family of G(q)-coupled receptors can regulate the activity of Rho and its downstream signaling pathways (PMID:12016230)
• regulation of signaling by ezrin-radixin-moesin-binding phosphoprotein-50 (PMID:12193606)
• Galpha protein signaling can lead to internalization of GPCRs, with specificity in both the Galpha proteins and GPCRs that are involved (PMID:12626493)
• Gq/11 proteins mediate KDR tyrosine phosphorylation and KDR-mediated HUVEC proliferation through interaction with KDR. (PMID:12670961)
• agonist binding to Gq-coupled receptors blocks Akt activation via the release of active Galphaq subunits that inhibit phosphatidylinositol 3-kinase (PMID:12704201)
• The rapid, shear-induced activation of Ras is mediated by Galpha(q) through the activity of Gbetagamma subunits in human vascular endothelial cells. (PMID:12714438)
• G protein-coupled receptors might evoke G alpha and G beta gamma to orchestrate regulation of phospholipase signaling by tubulin dimers and control of cell shape by microtubules (PMID:12807915)
• Gq-coupled receptors activate glycogen synthase kinase-3beta and C-terminal Src kinase (PMID:14561750)
• G alpha q and platelet activating factor receptor lead to stimulation of Src and focal adhesion kinase in vascular endothelium (PMID:14617636)
• the co-operative effect between Gbetagamma-mediated signaling and the increased intracellular Ca(2+) level represents a robust mechanism for the stimulation of JNK by G(q)-coupled receptors (PMID:15115661)
• (HEK) 293 cells expressing recombinant Galpha(q/11)-coupled muscarinic M3 receptors showed transient coexpression of RGS proteins (PMID:15383626)
• PC1 signaling elevates intracellular Ca(2+), activates Galpha(q) and PLC, which then activates calcineurin and NFAT (PMID:15466861)
• analysis of the GRK2 binding site of Galphaq (PMID:15471870)
• beta-Arrestin 1 and Galphaq/11 have roles in activating RhoA and stress fiber formation following receptor stimulation (PMID:15611106)
• These data indicate that the preserved integrity of plasma membrane domains/caveolae is required for complete agonist-induced phosphorylation of G(q)/G(11)alpha. (PMID:15694379)
• PKC epsilon and delta are the main PKC isozymes involved in G alpha(q)-mediated signaling in human atria (PMID:15698833)
• Galphaq potentiation of AC9 activity involves Ca2+/calmodulin and CaMKII. (PMID:15794946)
• Alpha-betagamma binding is necessary at a point downstream from receptor activation of the heterotrimeric G protein for signal transduction by alpha q. (PMID:16038796)
• Results suggest that the G(q) class proteins are degraded through the proteasome pathway and that cellular localization and/or other protein interactions determine their stability. (PMID:16218966)
• Quantitative analysis indicated that Galpha(q/11) subunits are abundant polypeptides in human brain, with values ranging from about 1200 ng/mg in cerebral cortex to close to 900 ng/mg of membrane protein in caudate (PMID:16481068)
• Our results support a novel model where activated Galpha(q) forms molecular complexes with ARNO and ARF6, possibly through a direct interaction with ARNO, leading to ARF6 activation. (PMID:16650966)
• alternative pathway operates in the absence of Lck-dependent tyrosine-phosphorylation events and was initiated by the T cell receptor-dependent activation of raft-enriched heterotrimeric Galpha11 proteins (PMID:16860758)
• Contractile dysfunction and pathological structural changes in the myocardium of Galpha(q) transgenic mice improve significantly after termination of the Galpha(q) signal, even in animals with overt heart failure. (PMID:16893886)
• GTP-Binding Protein alpha Subunits, Gq-G11, gene is regulated during megakaryocytic differentiation by early growth response 1 transcription factor. (PMID:16995904)
• Galphaq activation of TRPC6 signals the activation of PKCalpha, and thereby induces RhoA activity and endothelial cell contraction (PMID:17197445)
• These lines of evidence suggested that a Gq-coupled receptor activates specifically p38 MAPK through lipid rafts and Src kinase activation, in which flotillins positively modulate the Gq signaling. (PMID:17307333)
• two distinct regions of the Cav3.3 channel are necessary and sufficient for complete M1 receptor-mediated channel inhibition (PMID:17535809)
• Solubilization of this class of Galpha proteins was observed after prolonged agonist stimulation, induced by ultra high concentration of hormone and in cells expressing a large number of GPCRs, revealing tight binding of G(q)alpha protein to the membrane. (PMID:17552882)
• Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain (PMID:17606614)
• Polymorphism of the Galphaq gene is associated with accelerated mortality in heart failure (PMID:17720980)
• the crystal structure of the Galphaq-p63RhoGEF-RhoA complex, detailing the interactions of Galphaq with the Dbl and pleckstrin homology (DH and PH) domains of p63RhoGEF was determined (PMID:18096806)
• The M(1) receptor is the predominant mAChR subtype coupling to the Galpha(q/11) G protein in the cerebral cortex. (PMID:18322150)
• A novel polymorphism in the Gq promoter region is associated with enhanced promoter activity, Gq expression, intracellular signal transduction, and increased prevalence of left ventricular hypertrophy, particularly in women. (PMID:18326504)
• These novel data demonstrate an IKK2-dependent, predominantly G-protein-independent pathway involved in PAR-2 regulation of NFkappaB phosphorylation in keratinocytes. (PMID:18424071)
• IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Galphaq interaction and protein kinase C-alpha/CaMKII activation in H9c2 cardiomyoblast cells. (PMID:18434368)
• We show that Env-mediated Rac-1 activation is dependent on the activation of Galpha(q) and its downstream targets. (PMID:18632858)
• GNAQ mutations occur in about half of uveal melanomas, representing the most common known oncogenic mutation in this cancer. (PMID:18719078)
• MLK3 functions in a regulated way to limit levels of the activated GTPase Rho by binding to the Rho activator, p63RhoGEF/GEFT, which, in turn, prevents its activation by Galphaq. (PMID:18851832)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnaq	ENSDARG00000011487
danio_rerio	gna14	ENSDARG00000035178
rattus_norvegicus	Gnaq	ENSRNOG00000063937
drosophila_melanogaster	cta	FBGN0000384
drosophila_melanogaster	Galphai	FBGN0001104
drosophila_melanogaster	Galphaf	FBGN0010223
drosophila_melanogaster	CG17760	FBGN0033756
drosophila_melanogaster	CG30054	FBGN0050054
caenorhabditis_elegans		WBGENE00001664
caenorhabditis_elegans		WBGENE00001665
caenorhabditis_elegans		WBGENE00001666
caenorhabditis_elegans		WBGENE00001667
caenorhabditis_elegans		WBGENE00001668
caenorhabditis_elegans		WBGENE00001670
caenorhabditis_elegans		WBGENE00001671
caenorhabditis_elegans		WBGENE00001673
caenorhabditis_elegans		WBGENE00001674
caenorhabditis_elegans		WBGENE00001675
caenorhabditis_elegans	gpa-14	WBGENE00001676
caenorhabditis_elegans	gpa-16	WBGENE00001678
caenorhabditis_elegans	gsa-1	WBGENE00001745

Paralogs (15): GNA15 (ENSG00000060558), GNAI3 (ENSG00000065135), GNAO1 (ENSG00000087258), GNAS (ENSG00000087460), GNA11 (ENSG00000088256), GNAT1 (ENSG00000114349), GNAI2 (ENSG00000114353), GNA13 (ENSG00000120063), GNAI1 (ENSG00000127955), GNAZ (ENSG00000128266), GNAT2 (ENSG00000134183), GNAL (ENSG00000141404), GNA12 (ENSG00000146535), GNA14 (ENSG00000156049), GNAT3 (ENSG00000214415)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(q) subunit alpha — P50148 (reviewed: P50148)

Alternative names: Guanine nucleotide-binding protein alpha-q

All UniProt accessions (3): P50148, A0A024R240, B1AM21

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via phospholipase C-beta-dependent inositol lipid hydrolysis for signal propagation: activates phospholipase C-beta: following GPCR activation, GNAQ activates PLC-beta (PLCB1, PLCB2, PLCB3 or PLCB4), leading to production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Required for platelet activation. 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). Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs). Together with GNA11, required for heart development.

Subunit / interactions. G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts (GDP-bound form) with RIC8A (via C-terminus); promoting GNAQ folding and association with the plasma membrane. Binds NHERF1. Forms a complex with PECAM1 and BDKRB2. Interacts with GAS2L2. Interacts with CCKBR.

Subcellular location. Cell membrane. Golgi apparatus. Nucleus. Nucleus membrane.

Tissue specificity. Predominantly expressed in ovary, prostate, testis and colon. Down-regulated in the peripheral blood lymphocytes (PBLs) of rheumatoid arthritis patients (at protein level).

Post-translational modifications. Palmitoylated by ZDHHC3 and ZDHHC7. Palmitoylation occurs in the Golgi and participates in the localization of GNAQ to the plasma membrane. (Microbial infection) Deamidated at Gln-209 by Photorhabdus asymbiotica toxin PAU_02230, blocking GTP hydrolysis of heterotrimeric GNAQ or GNA11 and G-alphai (GNAI1, GNAI2 or GNAI3) proteins, thereby activating RhoA. Histaminylated at Gln-209 residues by TGM2.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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, intellectual disability, and recurrent stroke-like episodes. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G-alpha family. G(q) subfamily.

RefSeq proteins (1): NP_002063* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000654	Gprotein_alpha_Q	Family
IPR001019	Gprotein_alpha_su	Family
IPR011025	GproteinA_insert	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00503

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (74 total): helix 20, binding site 15, strand 10, sequence conflict 7, region of interest 5, turn 5, sequence variant 3, mutagenesis site 3, modified residue 2, lipid moiety-binding region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

37 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9VAW	ELECTRON MICROSCOPY	2.24
9M1H	ELECTRON MICROSCOPY	2.55
8THK	ELECTRON MICROSCOPY	2.6
8G59	ELECTRON MICROSCOPY	2.64
8XGO	ELECTRON MICROSCOPY	2.68
9K27	ELECTRON MICROSCOPY	2.68
9LL9	ELECTRON MICROSCOPY	2.76
7F6I	ELECTRON MICROSCOPY	2.8
8YYX	ELECTRON MICROSCOPY	2.84
7EZM	ELECTRON MICROSCOPY	2.9
7F6G	ELECTRON MICROSCOPY	2.9
7F6H	ELECTRON MICROSCOPY	2.9
8Y52	ELECTRON MICROSCOPY	2.9
8JPE	ELECTRON MICROSCOPY	2.91
8IYS	ELECTRON MICROSCOPY	2.95
8XGS	ELECTRON MICROSCOPY	2.95
9LLB	ELECTRON MICROSCOPY	2.98
7W3Z	ELECTRON MICROSCOPY	3
7W40	ELECTRON MICROSCOPY	3
8ZJD	ELECTRON MICROSCOPY	3.06
8JPB	ELECTRON MICROSCOPY	3.07
8JPC	ELECTRON MICROSCOPY	3.07
8ZJE	ELECTRON MICROSCOPY	3.07
7F8W	ELECTRON MICROSCOPY	3.1
7XOW	ELECTRON MICROSCOPY	3.1
8IA7	ELECTRON MICROSCOPY	3.1
8THL	ELECTRON MICROSCOPY	3.1
9D0A	ELECTRON MICROSCOPY	3.1
8YYW	ELECTRON MICROSCOPY	3.16
9LLA	ELECTRON MICROSCOPY	3.27

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50148-F1	93.13	0.84

Antibody-complex structures (SAbDab): 20 — 7DFL, 7EZM, 7F8W, 7W3Z, 7W40, 7XOW, 8G59, 8IA7, 8IYS, 8J9N, 8THK, 8THL, 8XGO, 8XGS, 8Y51, 8YYW, 8ZJD, 8ZJE, 9D0A, 9K27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (15): 53; 53; 54; 156; 180; 181; 183; 186; 274; 275; 277; 331 …

Post-translational modifications (4): 209, 209, 9, 10

Mutagenesis-validated functional residues (3):

Position	Phenotype
2	no effect on palmitoylation. no effect on phospholipase c-activating g protein-coupled receptor signaling pathway.
9	abolishes palmitoylation. inactive in phospholipase c-activating g protein-coupled receptor signaling pathway.
10	abolishes palmitoylation. inactive in phospholipase c-activating g protein-coupled receptor signaling pathway.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-112043	PLC beta mediated events
R-HSA-202040	G-protein activation
R-HSA-399997	Acetylcholine regulates insulin secretion
R-HSA-416476	G alpha (q) signalling events
R-HSA-418592	ADP signalling through P2Y purinoceptor 1
R-HSA-428930	Thromboxane signalling through TP receptor
R-HSA-434316	Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells

MSigDB gene sets: 700 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOCC_VACUOLAR_MEMBRANE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_PHOTOTRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_G_PROTEIN_COUPLED_GLUTAMATE_RECEPTOR_SIGNALING_PATHWAY, MODULE_16, AAAYRNCTG_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (21): adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), phospholipase C-activating G protein-coupled glutamate receptor signaling pathway (GO:0007206), phospholipase C-activating serotonin receptor signaling pathway (GO:0007208), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), glutamate receptor signaling pathway (GO:0007215), neuropeptide signaling pathway (GO:0007218), blood coagulation (GO:0007596), phototransduction, visible light (GO:0007603), entrainment of circadian clock (GO:0009649), hormone-mediated signaling pathway (GO:0009755), regulation of platelet activation (GO:0010543), response to prostaglandin E (GO:0034695), mast cell degranulation (GO:0043303), protein stabilization (GO:0050821), regulation of canonical Wnt signaling pathway (GO:0060828), cellular response to acidic pH (GO:0071468), sensory perception of itch (GO:0160025), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway (GO:0140582)

GO Molecular Function (12): G protein-coupled receptor binding (GO:0001664), GTPase activity (GO:0003924), G protein activity (GO:0003925), GTPase activator activity (GO:0005096), GTP binding (GO:0005525), G-protein beta/gamma-subunit complex binding (GO:0031683), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), guanyl nucleotide binding (GO:0019001), enzyme regulator activity (GO:0030234)

GO Cellular Component (12): photoreceptor outer segment (GO:0001750), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), nuclear membrane (GO:0031965), extracellular exosome (GO:0070062), postsynaptic cytosol (GO:0099524), nucleus (GO:0005634), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Signal amplification	2
Response of endothelial cells to shear stress	2
G-protein mediated events	1
Opioid Signalling	1
Regulation of insulin secretion	1
GPCR downstream signalling	1
Free fatty acids regulate insulin secretion	1
Platelet activation, signaling and aggregation	1
Chaperonin-mediated protein folding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
cellular anatomical structure	3
phospholipase C-activating G protein-coupled receptor signaling pathway	2
signal transduction	2
GTPase activity	2
molecular function regulator activity	2
catalytic activity	2
intracellular membrane-bounded organelle	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
PLC activating G protein-coupled glutamate receptor activity	1
G protein-coupled glutamate receptor signaling pathway	1
Gq/11-coupled serotonin receptor activity	1
G protein-coupled serotonin receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
cell surface receptor signaling pathway	1
glutamate receptor activity	1
hemostasis	1
wound healing	1
coagulation	1
phototransduction	1
detection of visible light	1
response to external stimulus	1
regulation of circadian rhythm	1
cellular response to hormone stimulus	1
platelet activation	1
regulation of cell activation	1
response to prostaglandin	1
response to alcohol	1
response to ketone	1
mast cell activation involved in immune response	1
mast cell mediated immunity	1
lysosome localization	1
leukocyte degranulation	1
establishment of organelle localization	1
regulation of protein stability	1
regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1

Protein interactions and networks

STRING

3056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNAQ	GRK2	P25098	995
GNAQ	GRM5	P41594	992
GNAQ	PLCB3	Q01970	990
GNAQ	S1PR3	Q99500	990
GNAQ	GRM1	Q13255	985
GNAQ	S1PR2	O95136	985
GNAQ	PLCB1	Q9NQ66	985
GNAQ	HRH1	P35367	978
GNAQ	SUCLG2	Q96I99	978
GNAQ	LPAR1	P78351	975
GNAQ	AGTR1	P30556	971
GNAQ	RGS2	P41220	960
GNAQ	RGS4	P49798	960
GNAQ	HTR2B	P41595	955
GNAQ	OXTR	P30559	953

IntAct

140 interactions, top by confidence:

A	B	Type	Score
CKS1B	CDK1	psi-mi:“MI:0914”(association)	0.920
EXOC6	EXOC5	psi-mi:“MI:0914”(association)	0.840
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
GNB1	GNG7	psi-mi:“MI:0914”(association)	0.640
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
GNG8	GNB5	psi-mi:“MI:0914”(association)	0.640
GNG5	GNB5	psi-mi:“MI:0914”(association)	0.620
GNAQ	Trpm8	psi-mi:“MI:0915”(physical association)	0.590
RARA	GNAQ	psi-mi:“MI:0915”(physical association)	0.560
RARA	GNAQ	psi-mi:“MI:2364”(proximity)	0.560
FYTTD1	UBA6	psi-mi:“MI:0914”(association)	0.530
HOXB5	VPS37C	psi-mi:“MI:0914”(association)	0.530
S1PR2	PALM3	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
SLC25A41	NUDT19	psi-mi:“MI:0914”(association)	0.530
CCNL2	ZBTB43	psi-mi:“MI:0914”(association)	0.530
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
ATG3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
RIC8A	VAPB	psi-mi:“MI:0914”(association)	0.530
GNG10	GNAS	psi-mi:“MI:0914”(association)	0.530
TACC3	HSPA8	psi-mi:“MI:0914”(association)	0.530
GNG2	GNB5	psi-mi:“MI:0914”(association)	0.530
GNG5	GNAS	psi-mi:“MI:0914”(association)	0.530

BioGRID (284): GNAQ (Reconstituted Complex), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS), GNAQ (Affinity Capture-MS)

ESM2 similar proteins: A8MTJ3, G1XJZ0, O14438, O15975, O70443, O73819, O95837, P04695, P04696, P0C7Q4, P11488, P16894, P19086, P19087, P19627, P20353, P20612, P21278, P21279, P28052, P29348, P29992, P30677, P38407, P38408, P38409, P41776, P43444, P45645, P50148, P50149, P82471, P87033, P87034, Q18434, Q21917, Q28294, Q28300, Q2PKF4, Q2XSV9

Diamond homologs: A8MTJ3, B0XRA0, B2RSH2, O13055, O13315, O15976, O42784, O70443, O73819, O74227, O74259, O95837, P04695, P04696, P04897, P04899, P08239, P08752, P08753, P08754, P09471, P0C7Q4, P0CN96, P0CN97, P10824, P10825, P11488, P16051, P16378, P16894, P18872, P19086, P19087, P19627, P20353, P20612, P21278, P21279, P27044, P27045

SIGNOR signaling

110 interactions.

A	Effect	B	Mechanism
AGTR1	up-regulates	GNAQ	binding
AGTR2	up-regulates	GNAQ	binding
CCKAR	up-regulates	GNAQ	binding
FZD3	up-regulates	GNAQ	binding
EDNRA	up-regulates	GNAQ	binding
LPAR6	up-regulates	GNAQ	binding
GNAQ	up-regulates	PLCE1	binding
GRPR	up-regulates	GNAQ	binding
PTGER1	up-regulates	GNAQ	binding
GNAQ	up-regulates	RHOA	binding
LPAR1	up-regulates	GNAQ	binding
GPER1	up-regulates	GNAQ	binding
KISS1R	“up-regulates activity”	GNAQ	binding
NMUR1	“up-regulates activity”	GNAQ	binding
TBXA2R	“up-regulates activity”	GNAQ	binding
P2RY13	“up-regulates activity”	GNAQ	binding
MC1R	“up-regulates activity”	GNAQ	binding
CHRM1	“up-regulates activity”	GNAQ	binding
TACR2	“up-regulates activity”	GNAQ	binding
MLNR	“up-regulates activity”	GNAQ	binding
AGTR1	“up-regulates activity”	GNAQ	binding
CHRM3	“up-regulates activity”	GNAQ	binding
CYSLTR1	“up-regulates activity”	GNAQ	binding
GALR2	“up-regulates activity”	GNAQ	binding
CYSLTR2	“up-regulates activity”	GNAQ	binding
AVPR1A	“up-regulates activity”	GNAQ	binding
PTGIR	“up-regulates activity”	GNAQ	binding
ADRA1B	“up-regulates activity”	GNAQ	binding
ADRA1D	“up-regulates activity”	GNAQ	binding
ADRB2	“up-regulates activity”	GNAQ	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Prostacyclin signalling through prostacyclin receptor	12	68.0×	2e-18
G beta:gamma signalling through BTK	11	65.8×	6e-17
ADP signalling through P2Y purinoceptor 12	13	60.9×	2e-18
G beta:gamma signalling through PLC beta	11	59.2×	2e-16
G beta:gamma signalling through CDC42	11	59.2×	2e-16
Presynaptic function of Kainate receptors	11	56.4×	4e-16
ADP signalling through P2Y purinoceptor 1	13	56.0×	2e-18
G-protein activation	12	53.9×	5e-17

GO biological processes:

GO term	Partners	Fold	FDR
fibroblast proliferation	5	14.6×	6e-03
positive regulation of ERK1 and ERK2 cascade	10	6.3×	3e-03
G protein-coupled receptor signaling pathway	23	6.2×	3e-09

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — HCC, NSCLC, SKCM, UM.

Clinical variants and AI predictions

ClinVar

69 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	17
Likely benign	16
Benign	17

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1172601	NM_002072.5(GNAQ):c.627A>C (p.Gln209His)	Pathogenic
1172602	NM_002072.5(GNAQ):c.627A>T (p.Gln209His)	Pathogenic
1285390	NM_002072.5(GNAQ):c.548G>T (p.Arg183Leu)	Pathogenic
2664271	NM_002072.5(GNAQ):c.547C>G (p.Arg183Gly)	Pathogenic
375955	NM_002072.5(GNAQ):c.626A>T (p.Gln209Leu)	Pathogenic
375956	NM_002072.5(GNAQ):c.626A>G (p.Gln209Arg)	Pathogenic

SpliceAI

3748 predictions. Top by Δscore:

Variant	Effect	Δscore
9:77721337:A:AC	donor_gain	1.0000
9:77721337:ACT:A	donor_gain	1.0000
9:77721338:C:CC	donor_gain	1.0000
9:77721338:CTC:C	donor_gain	1.0000
9:77721339:T:TA	donor_gain	1.0000
9:77721340:C:CA	donor_gain	1.0000
9:77721519:G:T	acceptor_gain	1.0000
9:77721522:C:CT	acceptor_gain	1.0000
9:77728508:ACTT:A	donor_loss	1.0000
9:77728509:CTT:C	donor_loss	1.0000
9:77728510:TTA:T	donor_loss	1.0000
9:77728511:TA:T	donor_loss	1.0000
9:77728512:A:AC	donor_gain	1.0000
9:77728512:A:AT	donor_loss	1.0000
9:77728513:C:CC	donor_gain	1.0000
9:77728513:C:CG	donor_loss	1.0000
9:77728513:CCAT:C	donor_gain	1.0000
9:77728664:GGTT:G	acceptor_gain	1.0000
9:77728666:TT:T	acceptor_gain	1.0000
9:77728667:TCTGG:T	acceptor_loss	1.0000
9:77728668:C:CC	acceptor_gain	1.0000
9:77728668:CTG:C	acceptor_loss	1.0000
9:77794456:CACTT:C	donor_loss	1.0000
9:77794457:ACTTA:A	donor_loss	1.0000
9:77794458:CTTA:C	donor_loss	1.0000
9:77794459:TTA:T	donor_loss	1.0000
9:77794460:TACCT:T	donor_loss	1.0000
9:77794461:A:C	donor_loss	1.0000
9:77794588:CCATT:C	acceptor_gain	1.0000
9:77794589:CATT:C	acceptor_gain	1.0000

AlphaMissense

2381 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:77721345:A:G	L353P	1.000
9:77721357:A:G	L349P	1.000
9:77721372:A:T	V344D	1.000
9:77721411:G:T	A331D	1.000
9:77728578:C:A	K275N	1.000
9:77728578:C:G	K275N	1.000
9:77728579:T:A	K275M	1.000
9:77728579:T:G	K275T	1.000
9:77728580:T:C	K275E	1.000
9:77728580:T:G	K275Q	1.000
9:77728581:G:C	N274K	1.000
9:77728581:G:T	N274K	1.000
9:77728588:A:G	F272S	1.000
9:77728591:A:G	L271P	1.000
9:77728642:A:G	L254P	1.000
9:77728642:A:T	L254H	1.000
9:77728650:G:C	S251R	1.000
9:77728650:G:T	S251R	1.000
9:77728652:T:G	S251R	1.000
9:77794482:A:T	L239H	1.000
9:77794488:T:G	Q237P	1.000
9:77794499:A:C	S233R	1.000
9:77794499:A:T	S233R	1.000
9:77794501:T:G	S233R	1.000
9:77794514:A:C	F228L	1.000
9:77794514:A:T	F228L	1.000
9:77794516:A:G	F228L	1.000
9:77794538:A:C	F220L	1.000
9:77794538:A:T	F220L	1.000
9:77794540:A:G	F220L	1.000

dbSNP variants (sampled 300 via entrez): RS1000000762 (9:77729084 C>T), RS1000010281 (9:77977892 T>C), RS1000019567 (9:77897105 C>T), RS1000019739 (9:77808324 C>T), RS1000066947 (9:77939126 T>C), RS1000070607 (9:77716588 C>G), RS1000080382 (9:77765336 G>A), RS1000084395 (9:78018030 T>C,G), RS1000087709 (9:77889422 A>C,G), RS1000087991 (9:77809500 T>A), RS1000097623 (9:77851326 G>A), RS1000106139 (9:77828878 C>A,G), RS1000141615 (9:77771560 G>C), RS1000146241 (9:78012030 T>C), RS1000151747 (9:78019637 T>C)

Disease associations

OMIM: gene MIM:600998 | disease phenotypes: MIM:163000, MIM:185300, MIM:149000

GenCC curated gene-disease

Disease	Classification	Inheritance
Sturge-Weber syndrome	Strong	Autosomal dominant
congenital hemangioma	Strong	Autosomal dominant

Mondo (6): familial multiple nevi flammei (MONDO:0008094), Sturge-Weber syndrome (MONDO:0008501), melanoma (MONDO:0005105), angioosteohypertrophic syndrome (MONDO:0007864), capillary malformation (MONDO:0016231), congenital hemangioma (MONDO:0018715)

Orphanet (6): Familial multiple nevi flammei (Orphanet:624), Sturge-Weber syndrome (Orphanet:3205), Rare capillary malformation (Orphanet:211247), OBSOLETE: Angioosteohypertrophic syndrome (Orphanet:2346), Capillary-lymphatic-venous malformation with segmental distribution (Orphanet:90308), NON RARE IN EUROPE: Melanoma (Orphanet:411533)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000212	Gingival overgrowth
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000329	Facial hemangioma
HP:0000364	Hearing abnormality
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000524	Conjunctival telangiectasia
HP:0000539	Abnormality of refraction
HP:0000541	Retinal detachment
HP:0000557	Buphthalmos
HP:0000572	Visual loss
HP:0000610	Abnormal choroid morphology
HP:0000612	Iris coloboma
HP:0000618	Blindness
HP:0000648	Optic atrophy
HP:0000689	Dental malocclusion
HP:0000708	Atypical behavior
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000969	Edema
HP:0000996	Facial capillary hemangioma
HP:0001034	Hypermelanotic macule
HP:0001052	Nevus flammeus
HP:0001098	Abnormal fundus morphology
HP:0001100	Heterochromia iridis
HP:0001123	Visual field defect
HP:0001131	Corneal dystrophy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008103_162	Bipolar disorder	6.000000e-06
GCST010796_1314	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1315	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007715	Klippel-Trenaunay-Weber Syndrome	C14.907.077.410
D008545	Melanoma	C04.557.465.625.650.510; C04.557.580.625.650.510; C04.557.665.510; C04.588.805.377; C17.800.882.445
D013341	Sturge-Weber Syndrome	C04.557.645.375.850; C10.562.800; C14.907.077.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3286079 (SINGLE PROTEIN), CHEMBL4523620 (PROTEIN FAMILY)

Clinical evidence (CIViC)

Drug × variant × indication: 8 predictive associations from 8 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
GNAQ Mutation	Trametinib	Uveal Melanoma	Sensitivity/Response	CIViC B	EID1229
GNAQ Mutation	Cabozantinib	Uveal Melanoma	Sensitivity/Response	CIViC B	EID5068
GNAQ Q209	Selumetinib	Uveal Melanoma	Sensitivity/Response	CIViC B	EID1213
GNAQ Q209	Refametinib	Uveal Melanoma	Sensitivity/Response	CIViC C	EID1233
GNAQ Q209P	Vemurafenib	Skin Melanoma	Resistance	CIViC C	EID1533
GNAQ Mutation	JQ1	Uveal Melanoma	Sensitivity/Response	CIViC D	EID1210
GNAQ Mutation	Sotrastaurin Acetate + Mirdametinib	Uveal Melanoma	Sensitivity/Response	CIViC D	EID1953
GNAQ Q209P	PLX4720	Skin Melanoma	Resistance	CIViC D	EID1537

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs60561071	GNAQ		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — G-alpha family G(q) subfamily

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
FR900359	Inhibition	7.48	pIC50
YM-254890	Inhibition	7.02	pIC50

ChEMBL bioactivities

19 potent at pChembl≥5 of 22 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.23	EC50	5.888	nM	CHEMBL5421352
8.16	EC50	6.918	nM	CHEMBL5421473
8.16	EC50	6.918	nM	CHEMBL5406651
8.15	EC50	7.079	nM	CHEMBL5423896
8.07	EC50	8.511	nM	CHEMBL5416714
8.05	EC50	8.913	nM	CHEMBL3104471
7.88	EC50	13.18	nM	CHEMBL5414487
7.86	EC50	13.8	nM	UROTENSIN-II
7.77	EC50	16.98	nM	CHEMBL5423896
7.73	EC50	18.62	nM	CHEMBL5421352
7.60	EC50	25.12	nM	CHEMBL5421473
7.55	EC50	28.18	nM	CHEMBL5416714
7.50	IC50	32	nM	CHEMBL4171381
7.46	EC50	34.67	nM	CHEMBL5406651
7.36	EC50	43.65	nM	CHEMBL5414487
7.00	IC50	100	nM	CHEMBL4288881
5.56	IC50	2754	nM	CHEMBL4873047

PubChem BioAssay actives

19 with measured affinity, of 192 total; 11 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-(4-aminobutyl)-5-[2-(4-hydroxyphenyl)ethyl]-2-oxo-1-[(4-phenylphenyl)methyl]-N-(3-phenylpropyl)-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019504: Antagonist activity at hUII-activated RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma by BRET assay (Rvb = 8.26 +/- 0.09 No_unit)	ec50	0.0059	uM
3-(4-aminobutyl)-5-[2-(4-hydroxyphenyl)ethyl]-2-oxo-N-(2-phenoxyethyl)-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019504: Antagonist activity at hUII-activated RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma by BRET assay (Rvb = 8.26 +/- 0.09 No_unit)	ec50	0.0069	uM
3-(4-aminobutyl)-N-(2,2-diphenylethyl)-5-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019504: Antagonist activity at hUII-activated RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma by BRET assay (Rvb = 8.26 +/- 0.09 No_unit)	ec50	0.0069	uM
3-(4-aminobutyl)-N-benzyl-5-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019504: Antagonist activity at hUII-activated RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma by BRET assay (Rvb = 8.26 +/- 0.09 No_unit)	ec50	0.0071	uM
3-(4-aminobutyl)-N-benzyl-5-[2-(4-hydroxyphenyl)ethyl]-N-methyl-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019504: Antagonist activity at hUII-activated RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma by BRET assay (Rvb = 8.26 +/- 0.09 No_unit)	ec50	0.0085	uM
(2S)-2-[[(4R,7S,10S,13S,16S,19R)-10-(4-aminobutyl)-19-[[(2S)-2-aminopropanoyl]amino]-16-benzyl-7-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-methylbutanoic acid	2019498: Agonist activity at RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma assessed as activation of Galpha-q by BRET assay	ec50	0.0089	uM
3-(4-aminobutyl)-N-benzyl-5-[(E)-2-(4-methoxyphenyl)ethenyl]-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019504: Antagonist activity at hUII-activated RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma by BRET assay (Rvb = 8.26 +/- 0.09 No_unit)	ec50	0.0132	uM
(4S)-4-amino-5-[[(2S,3R)-1-[(2S)-2-[[(2S)-1-[[(4R,7S,10S,13S,16S,19R)-10-(4-aminobutyl)-16-benzyl-4-[[(1S)-1-carboxy-2-methylpropyl]carbamoyl]-7-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-3-carboxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	2019498: Agonist activity at RLucII-tagged Galpha-q (unknown origin) expressed in HEK293 cells co-expressing human UT/GFP10-tagged G-gamma assessed as activation of Galpha-q by BRET assay	ec50	0.0138	uM
[(1R)-1-[(3S,6S,9S,12S,18R,21S,22R)-21-acetamido-18-benzyl-3-[(1R)-1-methoxyethyl]-4,9,10,12,16-pentamethyl-15-methylidene-2,5,8,11,14,17,20-heptaoxo-22-propan-2-yl-1,19-dioxa-4,7,10,13,16-pentazacyclodocos-6-yl]-2-methylpropyl] (2S,3R)-3-hydroxy-4-methyl-2-(propanoylamino)pentanoate	1749890: Inhibition of Galphaq/11 (unknown origin)	ic50	0.0320	uM
[(1R)-1-[(3S,6S,9S,12S,18R,21S,22R)-21-acetamido-18-benzyl-3-[(1R)-1-methoxyethyl]-4,9,10,12,16,22-hexamethyl-15-methylidene-2,5,8,11,14,17,20-heptaoxo-1,19-dioxa-4,7,10,13,16-pentazacyclodocos-6-yl]-2-methylpropyl] (2S,3R)-2-acetamido-3-hydroxy-4-methylpentanoate	1559769: Inhibition of G-alphaq/11 in human platelet rich plasma assessed as inhibition of ADP-mediated calcium ion mobilization	ic50	0.1000	uM
[(1R)-1-[(3Z,6S,9S,12S,18R,21S,22R)-21-acetamido-18-benzyl-3-ethylidene-4,9,10,12,16-pentamethyl-15-methylidene-2,5,8,11,14,17,20-heptaoxo-22-propan-2-yl-1,19-dioxa-4,7,10,13,16-pentazacyclodocos-6-yl]-2-methylpropyl] (2S,3S)-2-acetamido-3-hydroxy-4-methylpentanoate	1779418: Inhibition of wild type GNAQ (unknown origin) expressed in CRISPR/Cas9 engineered HEK293 cells	ic50	2.7542	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, increases reaction	4
Valproic Acid	decreases expression	3
bisphenol A	affects binding, affects folding, increases reaction, decreases reaction	2
sphingosine 1-phosphate	decreases reaction, increases expression, affects reaction	2
bisphenol S	affects expression, affects binding, decreases reaction	2
bisphenol AF	affects binding, affects folding, increases reaction, decreases reaction	2
aristolochic acid I	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	decreases methylation	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cicaprost	affects binding, increases reaction	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
perfluorobutanesulfonic acid	decreases expression, affects cotreatment, affects expression	1
asparanin A	decreases expression	1
trametinib	affects cotreatment, increases response to substance, increases cleavage	1
omipalisib	increases response to substance, increases cleavage, affects cotreatment	1
(+)-JQ1 compound	decreases reaction, increases response to substance, increases cleavage, decreases expression, affects binding (+2 more)	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Fingolimod Hydrochloride	decreases reaction, increases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3293153	Binding	Binding affinity to Galphaq (unknown origin) expressed in baculovirus-infected insect Hi5 cells assessed as inhibition of BODIPY FL GTPgammaS binding by measuring fluorescence reduction at 30 to 300 uM preincubated for 30 mins followed by B	Development of inhibitors of heterotrimeric Gαi subunits. — Bioorg Med Chem

Cellosaurus cell lines

56 cell lines: 26 cancer cell line, 25 spontaneously immortalized cell line, 5 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0B74	WM3618F	Cancer cell line	Female
CVCL_0B81	WM3772F	Cancer cell line	Female
CVCL_4D11	MP38	Cancer cell line	Male
CVCL_4D13	MP46	Cancer cell line	Male
CVCL_4D16	MM33	Cancer cell line	Sex unspecified
CVCL_5I90	CHO-K1 (+Gqi5) AequoScreen	Spontaneously immortalized cell line	Female
CVCL_8473	Mel20-06-039	Cancer cell line	Sex unspecified
CVCL_8474	Mel20-06-045	Cancer cell line	Sex unspecified
CVCL_8607	92-1 [Human uveal melanoma]	Cancer cell line	Female
CVCL_B6PW	TJU-UM001	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04999618	PHASE4	COMPLETED	A New Approach in Laser Surgery Using the Regenerative Solution in Children Diagnosed With Vascular Pathology
NCT02625389	PHASE4	COMPLETED	A Study to Evaluate How Safe and Effective is the Mixture of Lipiodol® Ultra Fluid and Glue When Used for Embolization Procedures
NCT03125057	PHASE4	COMPLETED	A Pilot Study of Hemoporfin PDT in Children With Port-wine Stain
NCT03181984	PHASE4	COMPLETED	Postmarketing Safety Study of Hemoporfin in Patients With Port Wine Stain
NCT04106258	PHASE4	COMPLETED	A Pilot Study of Hemoporfin PDT in Children(2-7 Years Old) With Port-wine Stain
NCT00324272	PHASE4	COMPLETED	Post-Operative Drainage Following Lymph Node Dissection
NCT01053819	PHASE4	COMPLETED	Can We Miss Pigmented Lesions in Psoriasis Patients?
NCT01898585	PHASE4	COMPLETED	An Open-Label Study of Zelboraf (Vemurafenib) in Patients With Braf V600 Mutation Positive Metastatic Melanoma
NCT02068196	PHASE4	ACTIVE_NOT_RECRUITING	A National Phase IV Study With Ipilimumab for Patients With Advanced Malignant Melanoma.
NCT02451488	PHASE4	COMPLETED	Neoadjuvant Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Cutaneous Stage L-lll Melanoma
NCT03313544	PHASE4	UNKNOWN	Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
NCT03340506	PHASE4	RECRUITING	Dabrafenib and/or Trametinib Rollover Study
NCT03715205	PHASE4	COMPLETED	Study to Evaluate the Safety of Pembrolizumab in Participants With Unresectable or Metastatic Melanoma or Non-small Cell Lung Cancer in India (MK-3475-593/KEYNOTE-593)
NCT04261179	PHASE4	UNKNOWN	Study Comparing Lymphoseek® vs. Albumin Nanocolloid in Head and Neck, Melanoma and Breast Cancer
NCT05467137	PHASE4	UNKNOWN	Sentinel Lymph Node Detection in Patients With Stage Ib-III Melanoma Using MSOT and ICG
NCT06116461	PHASE4	UNKNOWN	Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response
NCT06785974	PHASE4	NOT_YET_RECRUITING	Statins to Prevent Immune Checkpoint Inhibitor-induced PRogression of AtherosLerosis
NCT07004335	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Iparomlimab and Tuvonralimab Injection in Combination With Bevacizumab After Progression on Anti-PD-(L)1 Therapy in Advanced Melanoma: A Prospective, Single-Arm, Exploratory Clinical Study
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT07445022	PHASE4	RECRUITING	RWS of Tunlametinib in NRAS-Mutant Advanced Melanoma
NCT07504796	PHASE4	RECRUITING	ctDNA-guided Addition of Ipilimumab to Patients Receiving Nivolumab and Relatlimab
NCT07574047	PHASE4	NOT_YET_RECRUITING	MELCHRONO: A Prospective Randomized Study Investigating Chrono-immunotherapy for Advanced Melanoma.
NCT00001296	PHASE3	COMPLETED	A Randomized Phase III Trial of Hyperthermic Isolated Limb Perfusion With Melphalan, Tumor Necrosis Factor, and Interferon-Gamma in Patients With Locally Advanced Extremity Melanoma
NCT00002455	PHASE3	UNKNOWN	Immunotherapy After Surgery in Treating Patients With Breast Cancer, Colon Cancer, or Melanoma
NCT00002763	PHASE3	UNKNOWN	High-Dose or Low-Dose Interferon Alfa Compared With No Further Therapy Following Surgery in Treating Patients With Stage III Melanoma
NCT00002767	PHASE3	UNKNOWN	Interferon Alfa With or Without Vaccine Therapy in Treating Patients With Metastatic Melanoma
NCT00002882	PHASE3	COMPLETED	Interferon Alfa With or Without Combination Chemotherapy Plus Interleukin-2 in Treating Patients With Melanoma
NCT00002892	PHASE3	COMPLETED	Interferon Alfa or No Further Therapy Following Surgery in Treating Patients With Stage II, Stage III, or Recurrent Melanoma
NCT00003027	PHASE3	COMPLETED	Combination Chemotherapy With or Without Interleukin-2 and Interferon Alfa in Treating Patients With Metastatic Melanoma
NCT00003444	PHASE3	COMPLETED	Interferon Alfa-2b With or Without Radiation Therapy in Treating Patients With Melanoma That Has Metastasized to Lymph Nodes in the Neck, Under the Arm, or in the Groin
NCT00003641	PHASE3	ACTIVE_NOT_RECRUITING	High-Dose Interferon Alfa in Treating Patients With Stage II or Stage III Melanoma
NCT00003647	PHASE3	COMPLETED	Chemotherapy With or Without Immunotherapy in Treating Patients With Stage III or Stage IV Melanoma
NCT00003789	PHASE3	COMPLETED	Melphalan With or Without Tumor Necrosis Factor in Treating Patients With Locally Advanced Melanoma of the Arm or Leg
NCT00004196	PHASE3	COMPLETED	Interferon Alfa-2b in Treating Patients With Melanoma and Early Lymph Node Metastasis
NCT00005052	PHASE3	UNKNOWN	Vaccine Therapy in Treating Patients With Primary Stage II Melanoma
NCT00006237	PHASE3	COMPLETED	S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma
NCT00006249	PHASE3	UNKNOWN	Interferon Alfa Following Surgery in Treating Patients With Stage III Melanoma
NCT00016263	PHASE3	COMPLETED	Dacarbazine With or Without Oblimersen (G3139) in Treating Patients With Advanced Malignant Melanoma
NCT00019682	PHASE3	COMPLETED	Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma
NCT00020839	PHASE3	TERMINATED	Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain