GNA11

Summary

GNA11 (G protein subunit alpha 11, HGNC:4379) is a protein-coding gene on chromosome 19p13.3, encoding Guanine nucleotide-binding protein subunit alpha-11 (P29992). Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. In precision oncology, GNA11 Mutation confers sensitivity to Cabozantinib in Uveal Melanoma (CIViC Level B); 5 further curated variant–drug associations are listed below.

The protein encoded by this gene belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes one of the alpha subunits (subunit alpha-11). Mutations in this gene have been associated with hypocalciuric hypercalcemia type II (HHC2) and hypocalcemia dominant 2 (HYPOC2). Patients with HHC2 and HYPOC2 exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations.

Source: NCBI Gene 2767 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial hypocalciuric hypercalcemia 2 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 435 total — 9 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 93
• Druggable target: yes
• Precision-oncology evidence (CIViC): 6 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_002067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4379
Approved symbol	GNA11
Name	G protein subunit alpha 11
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FBH, FBH2, FHH2
Ensembl gene	ENSG00000088256
Ensembl biotype	protein_coding
OMIM	139313
Entrez	2767

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000078429, ENST00000586180, ENST00000586763, ENST00000587636, ENST00000588401, ENST00000590534, ENST00000591301

RefSeq mRNA: 1 — MANE Select: NM_002067 NM_002067

CCDS: CCDS12103

Canonical transcript exons

ENST00000078429 — 7 exons

Exon	Start	End
ENSE00000859533	3094362	3094787
ENSE00000859536	3114944	3115072
ENSE00001761812	3110149	3110333
ENSE00002906595	3120989	3123999
ENSE00003520728	3119206	3119359
ENSE00003613777	3118924	3119053
ENSE00003686698	3113330	3113484

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.9544 / max 522.0851, expressed in 1763 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173137	32.1692	1745
173136	2.8493	1444
173138	1.7625	1034
173140	0.9320	492
208643	0.1370	29
208642	0.1044	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.71	gold quality
jejunal mucosa	UBERON:0000399	97.79	gold quality
pancreatic ductal cell	CL:0002079	97.63	gold quality
duodenum	UBERON:0002114	97.58	gold quality
mucosa of transverse colon	UBERON:0004991	97.52	gold quality
secondary oocyte	CL:0000655	97.39	gold quality
cerebellar vermis	UBERON:0004720	97.14	gold quality
oocyte	CL:0000023	96.75	gold quality
parotid gland	UBERON:0001831	96.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.26	gold quality
jejunum	UBERON:0002115	96.01	gold quality
epithelial cell of pancreas	CL:0000083	95.98	gold quality
cerebellar cortex	UBERON:0002129	95.91	gold quality
cerebellar hemisphere	UBERON:0002245	95.90	gold quality
cerebellum	UBERON:0002037	95.87	gold quality
small intestine	UBERON:0002108	95.83	gold quality
stromal cell of endometrium	CL:0002255	95.80	gold quality
transverse colon	UBERON:0001157	95.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.53	gold quality
nipple	UBERON:0002030	95.48	gold quality
rectum	UBERON:0001052	95.37	gold quality
paraflocculus	UBERON:0005351	94.96	gold quality
colonic mucosa	UBERON:0000317	94.90	gold quality
saphenous vein	UBERON:0007318	94.89	gold quality
lower esophagus	UBERON:0013473	94.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.76	gold quality
intestine	UBERON:0000160	94.68	gold quality
seminal vesicle	UBERON:0000998	94.62	gold quality
colon	UBERON:0001155	94.58	gold quality
large intestine	UBERON:0000059	94.50	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, HOXB13, TBX18

miRNA regulators (miRDB)

87 targeting GNA11, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4510	100.00	66.60	2050
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-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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 40)

• the C-terminal domain participates intimately in the efficacy of B1R and B2R G(q/11) coupling by contributing both positive and negative regulatory epitopes. (PMID:12130679)
• GNA11 is involved in signalling of gonadotropin-releasing hormone receptor, which negatively regulates cell growth. Down-regulation is suggested to be involved in human breast cancers. (PMID:12759536)
• a new signaling pathway by which G alpha(q/11)-coupled receptors specifically induce Rho signaling through a direct interaction of activated G alpha(q/11) subunits with p63RhoGEF. (PMID:15632174)
• regulation of the PLC pathway through the PTH1R is significantly increased by elevating expression of G(11)alpha in osteoblastic cells. (PMID:15693018)
• TPO integrates G(i), but not G(q), stimulation, supports integrin alpha(IIb)beta(3) activation platelet aggregation independently of phospholipase C but requires PI3-kinase and Rap1B (PMID:15863506)
• These results indicate that the thio-acylation status of the alpha1b-adrenoceptor does not regulate G protein activation whereas thio-acylation of Galpha11 plays a key role in activation by the receptor. (PMID:16297597)
• soluble amyloid precursor protein release enhancement induced by muscarinic receptor stimulation was decreased by a G(q/11) minigene construct (PMID:16350855)
• CB(1) receptors are stabilized in a conformation that enables G(q)11 signaling by the WIN55212-2 cannabinoid agonist, thus shifting the G protein specificity of the receptor (PMID:16365309)
• the ability of MAS to up-regulate AT(1) receptor levels reflects the constitutive capacity of MAS to activate Galpha(q)/Galpha(11) and hence stimulate PKC-dependent phosphorylation of the AT(1) receptor (PMID:16611642)
• G(q/11)-coupled receptors are the principal G protein-coupled receptor subfamily mediating cooperative mitogenic signaling in airway smooth musscle. (PMID:16723377)
• The phosphorylation of Galpha11 protein represents a novel mechanism involved in regulation of receptor signaling. (PMID:17056873)
• 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(11)alpha protein to the membrane (PMID:17552882)
• Protein kinase C-related kinase and ROCK are required for thrombin-induced endothelial cell permeability downstream from Galpha12/13 and Galpha11/q (PMID:18713748)
• [review] Gq transgene activation mediates cardiac hypertrophy in vivo in response to pressure overload; transgenic mice with cardiac-specific deletion of Galphaq family proteins show no ventricular hypertrophy in response to pressure overload (PMID:20531218)
• Of the uveal melanomas we analyzed, 83% had somatic mutations in GNAQ or GNA11. (PMID:21083380)
• Benign and malignant blue nevi harbor frequent mutations in the Galphaq class of G-protein alpha subunits, Gnaq and Gna11 proteins. (PMID:21366456)
• Regulation of the epithelial Na+ channel by the RH domain of G protein-coupled receptor kinase, GRK2, and Galphaq/11. (PMID:21464134)
• The DNA obtained is of sufficient quality to carry out genotyping for markers on chromosome 3, 6 and 8, as well as screening for somatic mutations in GNAQ and GNA11 genes. (PMID:21945171)
• The presumed association of TRH-R with G(q/11)alpha proteins in plasma membranes was verified by RNAi experiments (PMID:22240728)
• The results expand the spectrum of GNA11 mutations that may occur in melanocytomas. (PMID:22307269)
• In primary melanocytic tumours, GNA11 and N-RAS mutations represent a mechanism of MAPK pathway activation alternative to the common GNAQ mutations (PMID:22758774)
• The vast majority of primary large uveal melanomas harbor mutually-exclusive mutations in GNAQ or GNA11, but very rarely have the oncogenic mutations that are reported commonly in other cancers. (PMID:22977135)
• Letter/Case Report: role of GNAQ/GNA11 mutational analysis in management of choroidal melanoma metastatic to the contralateral orbit. (PMID:23572068)
• This study identifies HRAS mutations in deep penetrating nevi. The presence of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi suggests classification of these nevi within the Spitz rather than the blue nevus category. (PMID:23599145)
• Mutant alleles of the GNA11 or GNAQ genes, which are highly specific for uveal melanoma, were identified in cell-free DNA of 9 of 22 (41%) patients. (PMID:23634288)
• GNAQ and GNA11 mutations are, in equal matter, not associated with uveal melanoma patient outcome. (PMID:23778528)
• Galpha11 mutants with loss of function cause familial hypocalciuric hypercalcemia type 2, and Galpha11 mutants with gain of function cause a clinical disorder designated as autosomal dominant hypocalcemia type 2. (PMID:23802516)
• Genomewide linkage analysis, combined with whole-exome sequencing, revealed two different heterozygous mutations affecting Galpha11 as novel causes of autosomal dominant isolated hypoparathyroidism. (PMID:23802536)
• There is a specific Egr-1 binding site at nt-475/-445. Egr-1 evoked an increased GNA11 transcription. (PMID:23802749)
• Metastatic uveal melanoma with GNAQ or GNA11 mutations is responsive to PKC inhibitors. (PMID:24141786)
• Increasing Galpha11 protein expression in osteoblasts can alter gene expression and result in a dual mechanism of trabecular bone loss. (PMID:24308950)
• the PECAM-1.Galphaq/11 mechanosensitive complex contains an endogenous heparan sulfate proteoglycan with HS chains that is critical for junctional complex assembly and regulating the flow response (PMID:24497640)
• melanopsin is a powerful optogenetic tool for the investigation of spatial and temporal aspects of Gq signalling in cardiovascular research (PMID:24576953)
• Our findings indicate that the germline gain-of-function mutation of GNA11 is a cause of autosomal dominant hypoparathyroidism and implicate a novel role for GNA11 in skeletal growth. (PMID:24823460)
• There was a significant association of GNA11 mutation status with metastatic status in uveal melanoma. (PMID:24970262)
• Oncogenic GNA11 mutation is associated with uveal melanoma. (PMID:25280020)
• review discusses the multiple activated signaling targets downstream of mutant GNAQ and GNA11 in uveal melanoma, including MEK, PI3-kinase/Akt, protein kinase C, and YAP (PMID:25304237)
• Involved in the MAPK/ERK, PI3K/AKT, and GNAQ/11 pathways. (PMID:25695059)
• Identification of Distinct Conformations of the Angiotensin-II Type 1 Receptor Associated with the Gq/11 Protein Pathway and the beta-Arrestin Pathway Using Molecular Dynamics Simulations. (PMID:25934394)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	gna15.1	ENSDARG00000016364
danio_rerio	gna15.2	ENSDARG00000056654
danio_rerio	gna15.4	ENSDARG00000071416
danio_rerio	si:ch211-207c7.2	ENSDARG00000092481
danio_rerio	gna15.3	ENSDARG00000092948
danio_rerio		ENSDARG00000116003
mus_musculus	Gna11	ENSMUSG00000034781
rattus_norvegicus	Gna11	ENSRNOG00000005446
drosophila_melanogaster	Galphaf	FBGN0010223
drosophila_melanogaster	CG17760	FBGN0033756
drosophila_melanogaster	CG30054	FBGN0050054
caenorhabditis_elegans		WBGENE00001664
caenorhabditis_elegans		WBGENE00001665
caenorhabditis_elegans		WBGENE00001667
caenorhabditis_elegans		WBGENE00001668
caenorhabditis_elegans		WBGENE00001670
caenorhabditis_elegans		WBGENE00001671
caenorhabditis_elegans		WBGENE00001673
caenorhabditis_elegans		WBGENE00001675
caenorhabditis_elegans	gpa-14	WBGENE00001676
caenorhabditis_elegans	gsa-1	WBGENE00001745

Paralogs (15): GNA15 (ENSG00000060558), GNAI3 (ENSG00000065135), GNAO1 (ENSG00000087258), GNAS (ENSG00000087460), GNAT1 (ENSG00000114349), GNAI2 (ENSG00000114353), GNA13 (ENSG00000120063), GNAI1 (ENSG00000127955), GNAZ (ENSG00000128266), GNAT2 (ENSG00000134183), GNAL (ENSG00000141404), GNA12 (ENSG00000146535), GNA14 (ENSG00000156049), GNAQ (ENSG00000156052), GNAT3 (ENSG00000214415)

Protein

Protein identifiers

Guanine nucleotide-binding protein subunit alpha-11 — P29992 (reviewed: P29992)

Alternative names: Guanine nucleotide-binding protein G(y) subunit alpha

All UniProt accessions (3): P29992, A0A087WVZ3, K7EL62

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, GNA11 activates PLC-beta (PLCB1, PLCB2, PLCB3 or PLCB4), leading to production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs). Together with GNAQ, required for heart development. In the respiratory epithelium, transmits OXGR1-dependent signals that lead to downstream intracellular Ca(2+) release and mucocilliary clearance of airborne pathogens.

Subunit / interactions. G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with RGS22. Interacts with NTSR1. (Microbial infection) Interacts with human cytomegalovirus (HHV-5) US28.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Expressed in testis.

Post-translational modifications. (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.

Disease relevance. Hypocalciuric hypercalcemia, familial 2 (HHC2) [MIM:145981] A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults. The disease is caused by variants affecting the gene represented in this entry. Hypocalcemia, autosomal dominant 2 (HYPOC2) [MIM:615361] A form of hypocalcemia, a disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. 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_002058* (*=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 (44 total): helix 8, strand 7, binding site 6, sequence variant 6, region of interest 5, sequence conflict 5, lipid moiety-binding region 2, turn 2, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
8QEH	X-RAY DIFFRACTION	1.43
8QEG	X-RAY DIFFRACTION	1.7
9P87	ELECTRON MICROSCOPY	2.8
9UCP	ELECTRON MICROSCOPY	2.88
7XXH	ELECTRON MICROSCOPY	2.9
9P86	ELECTRON MICROSCOPY	2.9
9P88	ELECTRON MICROSCOPY	2.9
6OIJ	ELECTRON MICROSCOPY	3.3
9UAP	ELECTRON MICROSCOPY	3.62
7TRY	ELECTRON MICROSCOPY	3.7
9P8A	ELECTRON MICROSCOPY	3.7
9P89	ELECTRON MICROSCOPY	3.9
7RKF	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29992-F1	93.04	0.83

Antibody-complex structures (SAbDab): 5 — 6OIJ, 7RKF, 7TRY, 7XXH, 9UCP

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 (6): 186; 274–277; 331; 46–53; 53; 180–183

Post-translational modifications (3): 209, 9, 10

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: 449 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, GOBP_REGULATION_OF_BLOOD_PRESSURE, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOCC_VACUOLAR_MEMBRANE, PEREZ_TP63_TARGETS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, KENNY_CTNNB1_TARGETS_UP, GOBP_PHOTOTRANSDUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5

GO Biological Process (21): skeletal system development (GO:0001501), action potential (GO:0001508), signal transduction (GO:0007165), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway (GO:0007207), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), heart development (GO:0007507), phototransduction, visible light (GO:0007603), regulation of blood pressure (GO:0008217), entrainment of circadian clock (GO:0009649), positive regulation of insulin secretion (GO:0032024), regulation of melanocyte differentiation (GO:0045634), developmental pigmentation (GO:0048066), phospholipase C-activating dopamine receptor signaling pathway (GO:0060158), cellular response to pH (GO:0071467), endothelin receptor signaling pathway (GO:0086100), cranial skeletal system development (GO:1904888), ligand-gated ion channel signaling pathway (GO:1990806), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating serotonin receptor signaling pathway (GO:0007208)

GO Molecular Function (11): G protein-coupled receptor binding (GO:0001664), GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), enzyme regulator activity (GO:0030234), 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)

GO Cellular Component (8): photoreceptor outer segment (GO:0001750), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), synapse (GO:0045202), extracellular exosome (GO:0070062), membrane (GO:0016020)

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	4
cellular anatomical structure	3
phospholipase C-activating G protein-coupled receptor signaling pathway	2
signal transduction	2
molecular function regulator activity	2
catalytic activity	2
system development	1
regulation of membrane potential	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase activity	1
phospholipase C activator activity	1
G protein-coupled acetylcholine receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
animal organ development	1
circulatory system development	1
phototransduction	1
detection of visible light	1
blood circulation	1
regulation of biological quality	1
response to external stimulus	1
regulation of circadian rhythm	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
melanocyte differentiation	1
regulation of pigment cell differentiation	1
pigmentation	1
G protein-coupled dopamine receptor signaling pathway	1
response to pH	1
cellular response to abiotic stimulus	1
anatomical structure development	1
ligand-gated monoatomic ion channel activity	1
G protein-coupled receptor activity	1
signaling receptor binding	1

Protein interactions and networks

STRING

1644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNA11	BRAF	P15056	797
GNA11	ARHGEF12	Q9NZN5	794
GNA11	BAP1	Q92560	792
GNA11	NRAS	P01111	790
GNA11	CASR	P41180	783
GNA11	EIF1AX	P47813	777
GNA11	KIT	P10721	773
GNA11	GNAQ	P50148	743
GNA11	PLCB4	Q15147	736
GNA11	SUCLG1	P53597	731
GNA11	S1PR4	O95977	718
GNA11	AP2S1	P53680	718
GNA11	ADRA1A	P35348	682
GNA11	SUCLG2	Q96I99	676
GNA11	CYSLTR2	Q9NS75	668

IntAct

98 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GNG8	GNB5	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
CD81	EGFR	psi-mi:“MI:0914”(association)	0.600
CD81	C2orf72	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
NOL7	IPO5	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
GNA11	AKT1	psi-mi:“MI:2364”(proximity)	0.470
BRAF	GNA11	psi-mi:“MI:2364”(proximity)	0.470
GNA11	AKT1	psi-mi:“MI:0915”(physical association)	0.470
BRAF	GNA11	psi-mi:“MI:0915”(physical association)	0.470
Actb		psi-mi:“MI:0914”(association)	0.350
Tpm1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Coro1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TMEM63B	CAV1	psi-mi:“MI:0914”(association)	0.350
CFTR		psi-mi:“MI:0914”(association)	0.350
CFTR	SNHG32	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DUSP22	POTEF	psi-mi:“MI:0914”(association)	0.350
GNG4	GNAI2	psi-mi:“MI:0914”(association)	0.350

BioGRID (131): GNA11 (Affinity Capture-Western), CXCR5 (Affinity Capture-Western), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), GNA11 (Co-fractionation), GNA11 (Co-fractionation)

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: A2Y3B5, A8MTJ3, B0XRA0, B2RSH2, O04278, O04279, O13055, O13315, O14438, O15976, O42784, O74227, O74259, O95837, P04695, P04696, P04897, P04899, P08239, P08752, P08753, P08754, P09471, P0C7Q4, P0CN96, P0CN97, P10824, P10825, P11488, P16378, P16894, P18064, P18872, P19087, P20353, P20612, P26981, P27044, P27045, P28051

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PLCB1	up-regulates	GNA11	binding
TRHR	“up-regulates activity”	GNA11	binding
GNA11	“up-regulates activity”	PLCB1	binding
AGTR1	“up-regulates activity”	GNA11	binding
ADRA1A	“up-regulates activity”	GNA11	binding
ADRA1B	“up-regulates activity”	GNA11	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 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	10	84.7×	8e-16
G beta:gamma signalling through BTK	9	80.4×	2e-14
ADP signalling through P2Y purinoceptor 12	11	76.9×	9e-17
G beta:gamma signalling through PLC beta	9	72.4×	6e-14
G beta:gamma signalling through CDC42	9	72.4×	6e-14
Presynaptic function of Kainate receptors	9	68.9×	1e-13
ADP signalling through P2Y purinoceptor 1	10	64.3×	1e-14
G beta:gamma signalling through PI3Kgamma	10	61.9×	1e-14

GO biological processes:

GO term	Partners	Fold	FDR
fibroblast proliferation	5	23.1×	1e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	12.4×	5e-03
Ras protein signal transduction	5	12.1×	5e-03
positive regulation of ERK1 and ERK2 cascade	8	8.0×	2e-03
G protein-coupled receptor signaling pathway	14	6.0×	9e-05
positive regulation of cell migration	8	5.8×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — MEL, UM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	9
Uncertain significance	159
Likely benign	189
Benign	40

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
155926	NM_002067.5(GNA11):c.179G>T (p.Arg60Leu)	Pathogenic
1691369	NM_002067.5(GNA11):c.626A>G (p.Gln209Arg)	Pathogenic
2423880	NC_000019.9:g.(?2901044)(3121449_?)del	Pathogenic
3238640	NM_002067.5(GNA11):c.627G>T (p.Gln209His)	Pathogenic
3774519	NM_002067.5(GNA11):c.546_547delinsTT (p.Arg183Cys)	Pathogenic
60661	NM_002067.5(GNA11):c.595ATC[1] (p.Ile200del)	Pathogenic
60662	NM_002067.5(GNA11):c.404T>A (p.Leu135Gln)	Pathogenic
60664	NM_002067.5(GNA11):c.1023C>G (p.Phe341Leu)	Pathogenic
60666	NM_002067.5(GNA11):c.632C>G (p.Ser211Trp)	Pathogenic
1285379	NM_002067.5(GNA11):c.161C>T (p.Thr54Met)	Likely pathogenic
1802938	NM_002067.5(GNA11):c.735+1G>A	Likely pathogenic
2498747	NM_002067.5(GNA11):c.625C>G (p.Gln209Glu)	Likely pathogenic
2576336	NM_002067.5(GNA11):c.741del (p.Met248fs)	Likely pathogenic
3583562	NM_002067.5(GNA11):c.446G>A (p.Arg149His)	Likely pathogenic
3765122	NM_002067.5(GNA11):c.826A>T (p.Lys276Ter)	Likely pathogenic
4279982	NM_002067.5(GNA11):c.548G>A (p.Arg183His)	Likely pathogenic
4540628	NM_002067.5(GNA11):c.535G>A (p.Val179Met)	Likely pathogenic
4755514	NM_002067.5(GNA11):c.548G>C (p.Arg183Pro)	Likely pathogenic

SpliceAI

1779 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3094783:GCTCG:G	donor_gain	1.0000
19:3094785:TCG:T	donor_gain	1.0000
19:3094788:G:GG	donor_gain	1.0000
19:3094789:T:A	donor_loss	1.0000
19:3110333:GGTG:G	donor_loss	1.0000
19:3110334:GTG:G	donor_loss	1.0000
19:3113480:AAGTA:A	donor_gain	1.0000
19:3113482:GTA:G	donor_gain	1.0000
19:3113483:TA:T	donor_gain	1.0000
19:3113485:G:GG	donor_gain	1.0000
19:3118918:TTTCA:T	acceptor_loss	1.0000
19:3118921:CAGG:C	acceptor_loss	1.0000
19:3118922:A:AG	acceptor_gain	1.0000
19:3118922:AG:A	acceptor_gain	1.0000
19:3118922:AGGAT:A	acceptor_gain	1.0000
19:3118923:G:GT	acceptor_gain	1.0000
19:3118923:GG:G	acceptor_gain	1.0000
19:3118923:GGA:G	acceptor_gain	1.0000
19:3118923:GGAT:G	acceptor_gain	1.0000
19:3118923:GGATG:G	acceptor_gain	1.0000
19:3119037:TG:T	donor_gain	1.0000
19:3119038:GG:G	donor_gain	1.0000
19:3119050:CGAG:C	donor_loss	1.0000
19:3119052:AGGT:A	donor_loss	1.0000
19:3119053:GGTG:G	donor_loss	1.0000
19:3119200:C:CA	acceptor_gain	1.0000
19:3119201:GCCA:G	acceptor_loss	1.0000
19:3119202:CCAG:C	acceptor_loss	1.0000
19:3119203:CAG:C	acceptor_loss	1.0000
19:3119204:A:AG	acceptor_gain	1.0000

AlphaMissense

2382 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3094776:T:C	L42P	1.000
19:3094779:T:A	L43Q	1.000
19:3094779:T:C	L43P	1.000
19:3094787:G:C	G46R	1.000
19:3094787:G:T	G46C	1.000
19:3110149:G:A	G46D	1.000
19:3110149:G:T	G46V	1.000
19:3110155:G:A	G48D	1.000
19:3110163:G:A	G51R	1.000
19:3110163:G:C	G51R	1.000
19:3110163:G:T	G51W	1.000
19:3110164:G:A	G51E	1.000
19:3110164:G:C	G51A	1.000
19:3110164:G:T	G51V	1.000
19:3110166:A:C	K52Q	1.000
19:3110167:A:T	K52M	1.000
19:3110168:G:C	K52N	1.000
19:3110168:G:T	K52N	1.000
19:3110169:A:C	S53R	1.000
19:3110169:A:T	S53C	1.000
19:3110170:G:T	S53I	1.000
19:3110171:C:A	S53R	1.000
19:3110171:C:G	S53R	1.000
19:3110173:C:A	T54K	1.000
19:3110183:G:C	K57N	1.000
19:3110183:G:T	K57N	1.000
19:3110186:G:C	Q58H	1.000
19:3110186:G:T	Q58H	1.000
19:3110191:G:C	R60P	1.000
19:3115006:T:C	L180P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002218 (19:3118292 G>A,C), RS1000047287 (19:3109160 T>C,G), RS1000062817 (19:3101991 G>C), RS1000140426 (19:3099216 G>A,T), RS1000188548 (19:3101574 C>G), RS1000422312 (19:3101860 G>A), RS1000450360 (19:3110837 C>G,T), RS1000469094 (19:3118742 C>T), RS1000657794 (19:3114836 C>T), RS1000689229 (19:3094613 G>A,C), RS1000695914 (19:3111329 C>A,G,T), RS1000703241 (19:3106673 C>G,T), RS1000719946 (19:3094405 C>T), RS1000812120 (19:3097613 C>A,T), RS1000846309 (19:3092806 A>T)

Disease associations

OMIM: gene MIM:139313 | disease phenotypes: MIM:145981, MIM:615361, MIM:255800, MIM:163000, MIM:146200, MIM:612918

GenCC curated gene-disease

Disease	Classification	Inheritance
familial hypocalciuric hypercalcemia 2	Strong	Autosomal dominant
autosomal dominant hypocalcemia 2	Strong	Autosomal dominant
congenital hemangioma	Strong	Autosomal dominant
autosomal dominant hypocalcemia	Supportive	Autosomal dominant

Mondo (10): familial hypocalciuric hypercalcemia 2 (MONDO:0007792), autosomal dominant hypocalcemia 2 (MONDO:0014146), Schwartz-Jampel syndrome type 1 (MONDO:0100435), vascular malformation (MONDO:0024291), familial multiple nevi flammei (MONDO:0008094), familial hypoparathyroidism (MONDO:0016390), CLOVES syndrome (MONDO:0013038), capillary malformation (MONDO:0016231), autosomal dominant hypocalcemia (MONDO:0018543), congenital hemangioma (MONDO:0018715)

Orphanet (7): Familial hypocalciuric hypercalcemia type 2 (Orphanet:101049), Familial isolated hypoparathyroidism (Orphanet:2238), Familial hypocalciuric hypercalcemia (Orphanet:405), Autosomal dominant hypocalcemia (Orphanet:428), Familial multiple nevi flammei (Orphanet:624), CLOVES syndrome (Orphanet:140944), Rare capillary malformation (Orphanet:211247)

HPO phenotypes

93 total (30 of 93 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000121	Nephrocalcinosis
HP:0000202	Orofacial cleft
HP:0000347	Micrognathia
HP:0000539	Abnormality of refraction
HP:0000541	Retinal detachment
HP:0000555	Leukocoria
HP:0000572	Visual loss
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000787	Nephrolithiasis
HP:0000821	Hypothyroidism
HP:0000934	Chondrocalcinosis
HP:0000951	Abnormality of the skin
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0000965	Cutis marmorata
HP:0000979	Purpura
HP:0001012	Multiple lipomas
HP:0001098	Abnormal fundus morphology
HP:0001231	Abnormal fingernail morphology
HP:0001250	Seizure
HP:0001511	Intrauterine growth retardation
HP:0001541	Ascites
HP:0001596	Alopecia
HP:0001597	Abnormal nail morphology

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009798_49	Asthma	7.000000e-10

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D054079	Vascular Malformations	C14.240.850; C16.131.240.850
C567863	Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi (supp.)
C537146	Hypocalciuric hypercalcemia, familial, type 2 (supp.)
C537156	Hypoparathyroidism familial isolated (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4295740 (SINGLE PROTEIN), CHEMBL4523620 (PROTEIN FAMILY)

Clinical evidence (CIViC)

Drug × variant × indication: 6 predictive associations from 6 curated evidence items; also 2 functional.

Variant	Therapy	Indication	Effect	Level	CIViC
GNA11 Mutation	Cabozantinib	Uveal Melanoma	Sensitivity/Response	CIViC B	EID3049
GNA11 Q209	Selumetinib	Uveal Melanoma	Sensitivity/Response	CIViC B	EID1212
NF1 Mutation OR GNA11 Q209L	Trametinib	Cancer	Sensitivity/Response	CIViC B	EID12027
GNA11 Mutation	Trametinib	Uveal Melanoma	Sensitivity/Response	CIViC C	EID1228
GNA11 Mutation	JQ1	Uveal Melanoma	Sensitivity/Response	CIViC D	EID1211
GNA11 Mutation	Mirdametinib + Sotrastaurin Acetate	Uveal Melanoma	Sensitivity/Response	CIViC D	EID1952

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

ChEMBL bioactivities

16 potent at pChembl≥5 of 20 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.50	IC50	32	nM	CHEMBL4171381
7.00	IC50	100	nM	CHEMBL4288881
6.82	IC50	150	nM	CHEMBL4288881
6.81	IC50	154.9	nM	CHEMBL4288881
6.51	IC50	309	nM	CHEMBL4173778
6.51	IC50	310	nM	CHEMBL4173778
6.06	IC50	880	nM	CHEMBL4278309
6.05	IC50	891.2	nM	CHEMBL4278309
5.72	IC50	1905	nM	CHEMBL4282827
5.72	IC50	1890	nM	CHEMBL4282827
5.63	IC50	2344	nM	CHEMBL4294526
5.63	IC50	2340	nM	CHEMBL4294526
5.43	IC50	3715	nM	CHEMBL4286619
5.43	IC50	3690	nM	CHEMBL4286619

PubChem BioAssay actives

16 with measured affinity, of 183 total; 7 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
[(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-[(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)-2-acetamido-3-hydroxy-4-methylpentanoate	1406732: Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubation for 1 hr at 37 degC measured after 15 mins at room temperature by HTRF assay	ic50	0.3090	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-(hexanoylamino)-3-hydroxy-4-methylpentanoate	1406732: Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubation for 1 hr at 37 degC measured after 15 mins at room temperature by HTRF assay	ic50	0.8800	uM
[(1R)-1-[(3S,6S,9S,12S,18R,21S)-21-acetamido-18-benzyl-3-[(1R)-1-methoxyethyl]-4,9,10,12,16-pentamethyl-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	1406732: Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubation for 1 hr at 37 degC measured after 15 mins at room temperature by HTRF assay	ic50	1.8900	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-benzamido-3-hydroxy-4-methylpentanoate	1406732: Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubation for 1 hr at 37 degC measured after 15 mins at room temperature by HTRF assay	ic50	2.3400	uM
[(1R)-1-[(3S,6S,9S,12S,18R,21S,22R)-21-acetamido-3-[(1R)-1-methoxyethyl]-4,9,10,12,16,22-hexamethyl-15-methylidene-18-(2-methylpropyl)-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	1406732: Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubation for 1 hr at 37 degC measured after 15 mins at room temperature by HTRF assay	ic50	3.6900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
bisphenol A	increases methylation, decreases expression, affects cotreatment	2
Arsenic	increases methylation, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
arsenite	increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
manganese chloride	increases abundance, increases expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
CP 31398	increases expression	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
perfluorobutanesulfonic acid	increases expression, affects cotreatment, affects expression	1
trametinib	increases response to substance	1
(+)-JQ1 compound	increases response to substance	1
bisphenol AF	increases expression	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
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases palmitoylation, decreases reaction	1
Cannabinoids	increases abundance, affects methylation	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4273833	Binding	Inhibition of recombinant human Gq/11 coupled N-terminal 3His-tagged M1 receptor expressed in CHOK1 cells assessed as reduction in carbachol-induced IP1 accumulation pretreated for 1 hr followed by carbachol addition and subsequent incubati	Structure-activity relationship and conformational studies of the natural product cyclic depsipeptides YM-254890 and FR900359. — Eur J Med Chem

Cellosaurus cell lines

22 cell lines: 22 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0D45	NZM083	Cancer cell line	Sex unspecified
CVCL_4D12	MP41	Cancer cell line	Female
CVCL_4D14	MP65	Cancer cell line	Female
CVCL_4D15	MM28	Cancer cell line	Male
CVCL_4D17	MM66	Cancer cell line	Sex unspecified
CVCL_6939	OMM-1	Cancer cell line	Male
CVCL_8475	Mel20-07-070	Cancer cell line	Sex unspecified
CVCL_C297	UPMD-1	Cancer cell line	Sex unspecified
CVCL_C298	UPMD-2	Cancer cell line	Sex unspecified
CVCL_C7VZ	T105	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00002146	PHASE4	COMPLETED	Safety and Efficacy of Intravenous Magnesium Sulfate in Modulating Changes in Symptoms and Divalent Cation Levels Associated With Foscavir Therapy: A Phase IV Randomized, Double-Blind, Placebo-Controlled, Cross-Over, Pilot Study
NCT00668200	PHASE4	COMPLETED	Impact on Reducing the Incidence of Low Serum Calcium by Providing Educational Materials on the Need to Take Daily Supplemental Calcium and Vitamin D to Patients With Paget’s Disease Treated With Reclast®
NCT01632514	PHASE4	UNKNOWN	Vitamin D Deficiency and Postoperative Hypocalcemia
NCT04012476	PHASE4	UNKNOWN	Determination of Parathyroid Function by Fluorescence With Indocyanine Green (ICG) After Total Thyroidectomy
NCT04412694	PHASE4	UNKNOWN	The Effect of Preoperative Oral Dexamethasone Supplementation on the Outcome of Thyroidectomised Patients.
NCT04491357	PHASE4	UNKNOWN	Prophylactic Infusion of Calcium Gluconate Reducing the Rate of Hypocalcaemia After Total Thyroidectomy
NCT05216419	PHASE4	COMPLETED	Prevention of Postoperative Hypocalcemia of Oral Vitamin D Supplementation Before Total Thyroidectomy
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
NCT04999618	PHASE4	COMPLETED	A New Approach in Laser Surgery Using the Regenerative Solution in Children Diagnosed With Vascular Pathology
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
NCT04750460	PHASE3	COMPLETED	Injection of Teriparatide to Prevent Hypocalcemia After Parathyroidectomy in Dialysis Patients (TeriCa).
NCT04775381	PHASE3	RECRUITING	Total Post-thyroidectomy Hypocalcemia After Preoperative Cholecalciferol Supplementation
NCT05680818	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1
NCT05953376	PHASE3	WITHDRAWN	Empiric Calcium in Massive Transfusion
NCT02384122	PHASE3	COMPLETED	Efficacy of Octreotide on Blood and Iron Requirements in Patients With Anemia Due to Angiodysplasias
NCT02638389	PHASE3	RECRUITING	Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care
NCT03110783	PHASE3	COMPLETED	Bioseal Dural Sealing Study BIOS-14-001
NCT03987152	PHASE3	UNKNOWN	Treatment of Congenital Vascular Malformations Using Sirolimus: Improving Quality of Life
NCT07285005	PHASE3	NOT_YET_RECRUITING	A Study to Investigate Efficacy and Safety of KP-001 Compared With Placebo in Patients Aged ≥2 Years With Common VM, Common LM, or KTS/CLOVES Syndrome
NCT02764411	PHASE3	TERMINATED	Onreltea (Brimonidine) Gel In Pediatric Patients With Capillary Malformations
NCT00001151	PHASE2	TERMINATED	Studies With 1,25-Dihydroxycholecalciferol
NCT00053378	PHASE2	COMPLETED	A Study to Examine the Use of Zemplar to Increase Serum Calcium Levels in ICU Subjects
NCT00623974	PHASE2	TERMINATED	Teriparatide (Forteo) in the Treatment of Patients With Postoperative Hypocalcemia
NCT00630214	PHASE2	COMPLETED	Prevention of Hypocalcemia in Patients Undergoing Total Thyroidectomy Plus Central Neck Dissection
NCT00743782	PHASE2	COMPLETED	Comparing Pump With Subcutaneous Injection Delivery of PTH 1-34 in the Management of Chronic Hypoparathyroidism
NCT01868750	PHASE2	COMPLETED	Phase II Pre-operative Vitamin D Supplementation to Prevent Post-thyroidectomy Hypocalcemia
NCT02204579	PHASE2	COMPLETED	A Study to Determine the Effects of NPSP795 on the Calcium-sensing Receptor in Subjects With Autosomal Dominant Hypocalcemia as Measured by PTH Levels and Blood Calcium Concentrations
NCT04581629	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1
NCT05732883	PHASE2	RECRUITING	The Use of Dexamethasone in Total Thyroidectomy to Improve Voice Outcome and Hypocalcaemia
NCT02509468	PHASE2	COMPLETED	suPERficial Slow-flow Vascular malFORMations Treated With sirolimUS
NCT02754960	PHASE2	WITHDRAWN	Efficacy Study of Thalidomide in Gastrointestinal Vascular Malformation Related Bleeding
NCT02883023	PHASE2	UNKNOWN	Electrosclerotherapy for Capillary Malformations
NCT03972592	PHASE2	COMPLETED	Topical Sirolimus in Cutaneous Lymphatic Malformations
NCT05983159	PHASE2	RECRUITING	A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
NCT06788314	PHASE2	RECRUITING	A Study of Enalapril in Treatment of Venous Malformations
NCT06789913	PHASE2	RECRUITING	A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation
NCT07037238	PHASE2	RECRUITING	An Open-Label, Single-Arm Exploratory Clinical Study of Everolimus for the Treatment of Vascular Malformations
NCT07477548	PHASE2	NOT_YET_RECRUITING	A Study to Evaluate the Efficacy and Safety of Everolimus in Patients With Teratment-refractory Vascular Anomalies