GNA12

Summary

GNA12 (G protein subunit alpha 12, HGNC:4380) is a protein-coding gene on chromosome 7p22.3-p22.2, encoding Guanine nucleotide-binding protein subunit alpha-12 (Q03113). Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.

Enables G protein activity; protein phosphatase 2A binding activity; and protein phosphatase activator activity. Involved in Rho-activating G protein-coupled receptor signaling pathway; regulation of TOR signaling; and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in lateral plasma membrane; neuron projection; and neuronal cell body. Is active in cytoplasm.

Source: NCBI Gene 2768 — RefSeq curated summary.

At a glance

• GWAS associations: 95
• Clinical variants (ClinVar): 31 total
• Druggable target: yes
• MANE Select transcript: NM_007353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4380
Approved symbol	GNA12
Name	G protein subunit alpha 12
Location	7p22.3-p22.2
Locus type	gene with protein product
Status	Approved
Aliases	gep
Ensembl gene	ENSG00000146535
Ensembl biotype	protein_coding
OMIM	604394
Entrez	2768

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000275364, ENST00000407653, ENST00000407904, ENST00000447791, ENST00000471281, ENST00000485329, ENST00000491117, ENST00000496740, ENST00000715274, ENST00000715275, ENST00000715276, ENST00000917992, ENST00000917993, ENST00000917994, ENST00000954394, ENST00000954395

RefSeq mRNA: 4 — MANE Select: NM_007353 NM_001282440, NM_001282441, NM_001293092, NM_007353

CCDS: CCDS5335, CCDS64583, CCDS64584

Canonical transcript exons

ENST00000275364 — 4 exons

Exon	Start	End
ENSE00000976187	2843853	2844308
ENSE00000976188	2794928	2795143
ENSE00003627659	2733451	2733501
ENSE00004026418	2728105	2731750

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.5754 / max 394.1826, expressed in 1806 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82516	22.3708	1804
82515	0.6881	440
82507	0.3816	185
82514	0.1114	36
82513	0.0236	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.47	gold quality
stromal cell of endometrium	CL:0002255	96.88	gold quality
oocyte	CL:0000023	96.09	gold quality
medial globus pallidus	UBERON:0002477	95.82	gold quality
globus pallidus	UBERON:0001875	94.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.91	gold quality
amygdala	UBERON:0001876	94.90	gold quality
nucleus accumbens	UBERON:0001882	94.55	gold quality
spinal cord	UBERON:0002240	94.22	gold quality
putamen	UBERON:0001874	93.76	gold quality
caudate nucleus	UBERON:0001873	93.44	gold quality
substantia nigra	UBERON:0002038	93.31	gold quality
right coronary artery	UBERON:0001625	93.21	gold quality
midbrain	UBERON:0001891	93.05	gold quality
ventricular zone	UBERON:0003053	92.96	gold quality
left ovary	UBERON:0002119	92.77	gold quality
popliteal artery	UBERON:0002250	92.75	gold quality
tibial artery	UBERON:0007610	92.75	gold quality
saphenous vein	UBERON:0007318	92.52	gold quality
left coronary artery	UBERON:0001626	92.48	gold quality
coronary artery	UBERON:0001621	92.33	gold quality
ganglionic eminence	UBERON:0004023	92.29	gold quality
right ovary	UBERON:0002118	92.27	gold quality
hypothalamus	UBERON:0001898	92.17	gold quality
right atrium auricular region	UBERON:0006631	92.12	gold quality
temporal lobe	UBERON:0001871	92.09	gold quality
aorta	UBERON:0000947	91.92	gold quality
Ammon’s horn	UBERON:0001954	91.82	gold quality
right frontal lobe	UBERON:0002810	91.78	gold quality
subthalamic nucleus	UBERON:0001906	91.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.74

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
RFFL	Activation

miRNA regulators (miRDB)

107 targeting GNA12, 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-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-199A-3P	99.75	70.48	929

Literature-anchored findings (GeneRIF, showing 40)

• Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin (PMID:11976333)
• Hsp90 binding and acylation of Galpha12 results in localization to lipid rafts (PMID:12117999)
• co-stimulation of G(12/13) and G(i) pathways is sufficient to activate GPIIb/IIIa in human platelets in a mechanism that involves intracellular calcium (PMID:12297512)
• Rho activation through Galpha12 and the regulation of RhoGEFs by heterotrimeric G proteins G1213 is further modulated by tyrosine phosphorylated leukemia-associated RhoGEF. (PMID:12515866)
• Selective activation of Galpha(12) and Galpha(13) by thrombin and LPA, respectively, is determined by the N-terminal short sequences of alpha subunits. (PMID:12594220)
• Galpha12-p120ctn interaction acts as a molecular switch, which regulates cadherin-mediated cell-cell adhesion. (PMID:15240885)
• Galpha12 has a role in direct regulation of PP2A activity and tau phosphorylation (PMID:15525651)
• An altered form of G alpha 12 is identified that is selectively uncoupled from one signaling pathway (RhoGEF) while retaining signaling capacity through a separate pathway (effector protein E-cadherin). (PMID:15746095)
• G alpha12 interaction with alphaSNAP induces VE-cadherin localization at endothelial junctions and regulates barrier function (PMID:15980433)
• Galpha12 plays a role in polarity and tail formation as spermatids mature. Furthermore, Galpha12 may be a candidate protein responsible for azoospermia caused by spermatogenic disturbance or midpiece deformities. (PMID:16612612)
• G12 has a role in breast cancer invasion (PMID:16705036)
• Results identify the G12 family proteins Galpha12 and 13 as important regulators of prostate cancer invasion and suggest that these proteins may be targeted to limit invasion- and metastasis-induced prostate cancer patient mortality. (PMID:16787920)
• G alpha(12/13) regulate basal p53 levels via mdm4, which constitutes a cell signaling pathway distinct from p53 phosphorylations elicited by genotoxic stress. (PMID:17510313)
• mechanisms of thrombin-stimulated apoptosis through endogenous Galpha12 included loss of Bcl-2, JNK activation, and up-regulation of IkappaBalpha (PMID:17565996)
• provides first examination of Galpha12 and Galpha13 in the human heart, demonstrating selective activation of human atrial Galpha12 and Galpha13 by endothelin and angiotensin receptors, respectively (PMID:17878759)
• The role of RBaK, PMS2, and GNA12 in the inheritance of familial hyperaldosteronism type II were studied. (PMID:18307725)
• A pronounced and rapid translocation of p115-RhoGEF from the cytosol to the plasma membrane was observed upon activation of several G(12/13)-coupled receptors in a cell type-independent fashion. (PMID:18320579)
• G alpha12Q229L variants uncoupled from RhoGEFs (but not fully functional activated G alpha12Q229L) induced transformation of the mitochondrial network into punctate mitochondria and resulted in a loss of mitochondrial membrane potential. (PMID:18367648)
• AC7 is a specific downstream effector of the G(12/13) pathway (PMID:18541530)
• Protein kinase C-related kinase and ROCK are required for thrombin-induced endothelial cell permeability downstream from Galpha12/13 and Galpha11/q (PMID:18713748)
• These results indicate that activation of Galpha(12/13) in cardiomyocytes by the extracellular nucleotides-stimulated P2Y(6) receptor triggers fibrosis in pressure overload-induced cardiac fibrosis (PMID:19008857)
• This review gives an overview of Galpha12/13 signaling of G protein-coupled receptors with a focus on RhoGTPase nucleotide exchange factor (RhoGEF) proteins as the immediate mediators of G12/13 activation. (PMID:19226283)
• This review describes the signaling pathways and cellular events stimulated by Galpha12 proteins with an emphasis on processes important in regulating cell migration and invasion and potentially involved in the pathophysiology of cancer metastasis. (PMID:19422395)
• Enhancement of choline kinase activation and phosphocholine production in breast cancer cells occurs via a CaR-Galpha12-Rho signaling pathway. (PMID:19716891)
• TXA(2) receptor mediates water influx through aquaporins in astrocytoma cells via TXA(2) receptor-mediated activation of G alpha(12/13), Rho A, Rho kinase and Na(+)/H(+)-exchanger. (PMID:19772916)
• Galpha12/13 upregulate matrix metalloproteinase-2 via p53 promoting human breast cell invasion. (PMID:20044778)
• G(alpha)(12) and G(alpha)13) exert a complex pattern of nonredundant effects in small cell lung cancer cells (PMID:20160064)
• Mutations of Galpha12 in its PC1-binding regions do not affect the ability to stimulate apoptosis are uncoupled from polycystin-1 regulation. (PMID:20837139)
• Galpha(12/13) regulate AP-1-dependent CYR61 induction in vascular smooth muscle, promoting migration, and they are upregulated with CYR61 in arteriosclerotic lesions. (PMID:21212405)
• Overexpression of Galpha(s) or Galpha(12) active mutants enhanced androgen-induced androgen receptor transactivation. Galpha(s) active mutant sensitized androgen receptor to castration-level of androgen (R1881). (PMID:21308712)
• A functional role for JLP in the gep oncogene-regulated neoplastic signaling pathway. (PMID:21472140)
• Negative regulation of Gq-mediated pathways in platelets by G(12/13) pathways through Fyn kinase (PMID:21592972)
• In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension (PMID:21986993)
• study implicates a G12-stimulated mitogen-activated protein kinase cascade in cancer cell invasion, and supports a role for JNK in cancer progression. (PMID:22087220)
• that Galpha(i2)-induced signaling can act as a counterbalance to MuRF1-mediated atrophy, indicating that receptors that act through Galpha(i2) might represent potential targets for preventing skeletal muscle wasting. (PMID:22126963)
• Ga12 activation in podocytes leads to cumulative changes in glomerular collagen expression,proteinuria and glomerulosclerosis. (PMID:22249312)
• Galpha12 drives oral squamous cell carcinoma invasion through the up-regulation of IL-6 and IL-8 cytokines. (PMID:23762476)
• CREB is a critical signaling node in Lysophosphatidic acid-Lysophosphatidic acid receptor and Galpha12/gep proto-oncogene stimulated oncogenic signaling in ovarian cancer cells. (PMID:24055910)
• A tyrosine residue at the C-terminus of the Galpha subunit plays an important role in controlling activation of G-protein coupled receptors. (PMID:24464644)
• Galpha12gep oncogene inhibits FOXO1, which may result from the inhibition of FOXO1 de novo synthesis by miR-135b in conjunction with MDM2-mediated destabilization of FOXO1. (PMID:24631529)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000115627
mus_musculus	Gna12	ENSMUSG00000000149
rattus_norvegicus	Gna12	ENSRNOG00000001235
drosophila_melanogaster	cta	FBGN0000384
drosophila_melanogaster	Galphai	FBGN0001104
drosophila_melanogaster	Galphaf	FBGN0010223
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), GNA14 (ENSG00000156049), GNAQ (ENSG00000156052), GNAT3 (ENSG00000214415)

Protein

Protein identifiers

Guanine nucleotide-binding protein subunit alpha-12 — Q03113 (reviewed: Q03113)

All UniProt accessions (3): Q03113, C9J2Y7, E9PC54

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins. Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating pro-inflammatory cytokine production. Inhibits CDH1-mediated cell adhesion in process independent from Rho activation. Together with NAPA promotes CDH5 localization to plasma membrane. May play a role in the control of cell migration through the TOR signaling cascade.

Subunit / interactions. G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with UBXD5. Interacts (in GTP-bound form) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Interacts with RGS22. Interacts (via N-terminus) with NAPA; the interaction promotes CDH5 localization to plasma membrane. Interacts with CTNND1 (via N-terminus); the interaction regulates CDH1-mediated cell-cell adhesion. Interacts with PPP2R1A; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT. Interacts (in GTP-bound form) with ARHGEF1. Interacts (in GTP-bound form) with ARHGEF11 (via RGS domain). Interacts (in GTP-bound form) with ARHGEF12 (via RGS domain).

Subcellular location. Cell membrane. Lateral cell membrane. Cytoplasm.

Similarity. Belongs to the G-alpha family. G(12) subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q03113-1	1	yes
Q03113-2	2
Q03113-3	3

RefSeq proteins (4): NP_001269369, NP_001269370, NP_001280021, NP_031379* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000469	Gprotein_alpha_12/13	Family
IPR001019	Gprotein_alpha_su	Family
IPR011025	GproteinA_insert	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00503

UniProt features (39 total): helix 10, binding site 6, strand 6, region of interest 5, splice variant 3, sequence variant 3, sequence conflict 2, chain 1, domain 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7YDJ	ELECTRON MICROSCOPY	3.03

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03113-F1	89.96	0.79

Antibody-complex structures (SAbDab): 1 — 7YDJ

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): 208; 296–299; 353; 67–72; 71; 202–205

Post-translational modifications (2): 208, 11

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)

MSigDB gene sets: 306 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MULLIGHAN_NPM1_SIGNATURE_3_UP, WANG_CLIM2_TARGETS_UP, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, KEGG_MAPK_SIGNALING_PATHWAY, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (18): in utero embryonic development (GO:0001701), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), Rho protein signal transduction (GO:0007266), blood coagulation (GO:0007596), regulation of blood pressure (GO:0008217), regulation of cell shape (GO:0008360), response to xenobiotic stimulus (GO:0009410), regulation of fibroblast migration (GO:0010762), cell differentiation (GO:0030154), regulation of TOR signaling (GO:0032006), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), embryonic digit morphogenesis (GO:0042733), Rho-activating G protein-coupled receptor signaling pathway (GO:0160221), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706), negative regulation of vascular associated smooth muscle cell migration (GO:1904753), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556)

GO Molecular Function (12): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), G-protein beta/gamma-subunit complex binding (GO:0031683), D5 dopamine receptor binding (GO:0031752), metal ion binding (GO:0046872), protein phosphatase 2A binding (GO:0051721), protein phosphatase activator activity (GO:0072542), nucleotide binding (GO:0000166), G protein-coupled receptor binding (GO:0001664), protein binding (GO:0005515), guanyl nucleotide binding (GO:0019001)

GO Cellular Component (9): cytoplasm (GO:0005737), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), focal adhesion (GO:0005925), lateral plasma membrane (GO:0016328), brush border membrane (GO:0031526), neuron projection (GO:0043005), neuronal cell body (GO:0043025), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
G protein-coupled receptor signaling pathway	2
regulation of biological quality	2
intracellular anatomical structure	2
chordate embryonic development	1
G protein-coupled receptor activity	1
adenylate cyclase activity	1
small GTPase-mediated signal transduction	1
hemostasis	1
wound healing	1
coagulation	1
blood circulation	1
regulation of cell morphogenesis	1
response to chemical	1
fibroblast migration	1
regulation of cell migration	1
cellular developmental process	1
TOR signaling	1
regulation of intracellular signal transduction	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
regulation of proteasomal protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
negative regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
negative regulation of smooth muscle cell migration	1
vascular associated smooth muscle cell migration	1
regulation of vascular associated smooth muscle cell migration	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1

Protein interactions and networks

STRING

2670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNA12	ARHGEF12	Q9NZN5	997
GNA12	ARHGEF1	Q92888	991
GNA12	ARHGEF11	O15085	987
GNA12	GPR55	Q9Y2T6	982
GNA12	ADGRG1	Q9Y653	952
GNA12	LPAR6	P43657	948
GNA12	LPAR1	P78351	947
GNA12	S1PR3	Q99500	935
GNA12	S1PR2	O95136	919
GNA12	S1PR5	Q9H228	905
GNA12	TJP1	Q07157	884
GNA12	RHOA	P06749	881
GNA12	GNA13	Q14344	860
GNA12	S1PR4	O95977	848
GNA12	LPAR2	Q9HBW0	843

IntAct

35 interactions, top by confidence:

A	B	Type	Score
EMC7	EMC8	psi-mi:“MI:0914”(association)	0.790
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
GNG8	GNB5	psi-mi:“MI:0914”(association)	0.640
GNAS	CPT2	psi-mi:“MI:0914”(association)	0.530
RIC8A	VAPB	psi-mi:“MI:0914”(association)	0.530
ERBB2	HAX1	psi-mi:“MI:0914”(association)	0.530
H1-5	GNA12	psi-mi:“MI:0915”(physical association)	0.400
GNA12	PPP2R1A	psi-mi:“MI:0915”(physical association)	0.400
GNA12	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
IL3RA	GNA12	psi-mi:“MI:0915”(physical association)	0.370
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
GNB1	TP53I11	psi-mi:“MI:0914”(association)	0.350
GNG2	FAM171A2	psi-mi:“MI:0914”(association)	0.350
GNAS	RANBP6	psi-mi:“MI:0914”(association)	0.350
GNGT1	GNAS	psi-mi:“MI:0914”(association)	0.350
GNA13	HSPA8	psi-mi:“MI:0914”(association)	0.350
RIC8A	GNA11	psi-mi:“MI:0914”(association)	0.350
GNAS	CPT2	psi-mi:“MI:0914”(association)	0.350
ATF2	ABLIM1	psi-mi:“MI:0914”(association)	0.350
MYC	ALB	psi-mi:“MI:0914”(association)	0.350
STAT3	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
ATF2	AGPS	psi-mi:“MI:0914”(association)	0.350
CEBPA	HAX1	psi-mi:“MI:0914”(association)	0.350
ERBB2	AP3B1	psi-mi:“MI:0914”(association)	0.350
MYB	C11orf98	psi-mi:“MI:0914”(association)	0.350
MYC	AP3B1	psi-mi:“MI:0914”(association)	0.350
STAT3	HAX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): GNA12 (Phenotypic Enhancement), GNA12 (Affinity Capture-MS), GNA12 (Affinity Capture-MS), GNA12 (Affinity Capture-MS), CDH15 (Reconstituted Complex), GNA12 (Reconstituted Complex), GNA12 (Reconstituted Complex), GNA12 (Affinity Capture-RNA), GNA12 (Affinity Capture-Western), GNA12 (Reconstituted Complex), GNA12 (Affinity Capture-Western), GNA12 (Proximity Label-MS), GNA12 (Positive Genetic), GNA12 (Affinity Capture-RNA), GNA12 (Affinity Capture-Western)

ESM2 similar proteins: B0XRA0, B2RSH2, G1XJZ0, O13315, O42784, O74227, O74259, P04897, P04899, P08752, P08753, P08754, P10824, P10825, P16378, P18872, P20353, P27044, P27045, P27600, P27601, P30675, P30676, P38400, P38401, P38402, P38403, P41776, P50146, P50147, P51876, P59215, P59216, P63096, P63097, P87032, P87383, Q00580, Q00743, Q03113

Diamond homologs: A8MTJ3, B0XRA0, B2RSH2, O13055, O13315, O15975, O15976, O42784, O70443, O73819, O74227, O74259, O88302, O95837, P04695, P04696, P04897, P04899, P08239, P08752, P08753, P08754, P09471, P0C7Q4, P10824, P10825, P11488, P16378, P18872, P19086, P19087, P19627, P20353, P20612, P21278, P21279, P23625, P27044, P27045, P27600

SIGNOR signaling

58 interactions.

A	Effect	B	Mechanism
NMBR	up-regulates	GNA12	binding
FZD3	up-regulates	GNA12	binding
LPAR2	up-regulates	GNA12	binding
LPAR3	up-regulates	GNA12	binding
LPAR1	up-regulates	GNA12	binding
GNA12	up-regulates	RHOA	binding
F2RL3	up-regulates	GNA12	binding
S1PR2	up-regulates	GNA12	binding
F2R	up-regulates	GNA12	binding
GNA12	“up-regulates activity”	ARHGEF11	binding
FFAR3	“up-regulates activity”	GNA12	binding
SSTR1	“up-regulates activity”	GNA12	binding
SSTR4	“up-regulates activity”	GNA12	binding
P2RY2	“up-regulates activity”	GNA12	binding
LTB4R	“up-regulates activity”	GNA12	binding
ADRA2B	“up-regulates activity”	GNA12	binding
GPR183	“up-regulates activity”	GNA12	binding
PTGER3	“up-regulates activity”	GNA12	binding
GPR35	“up-regulates activity”	GNA12	binding
LPAR5	“up-regulates activity”	GNA12	binding
MLNR	“up-regulates activity”	GNA12	binding
P2RY13	“up-regulates activity”	GNA12	binding
PTGER1	“up-regulates activity”	GNA12	binding
CNR1	“up-regulates activity”	GNA12	binding
LPAR6	“up-regulates activity”	GNA12	binding
P2RY10	“up-regulates activity”	GNA12	binding
GALR2	“up-regulates activity”	GNA12	binding
FFAR1	“up-regulates activity”	GNA12	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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	6	106.1×	2e-09
Thromboxane signalling through TP receptor	7	98.0×	2e-10
G beta:gamma signalling through BTK	5	93.3×	5e-08
ADP signalling through P2Y purinoceptor 12	6	87.6×	4e-09
G-protein activation	6	84.0×	4e-09
G beta:gamma signalling through PLC beta	5	84.0×	6e-08
G beta:gamma signalling through CDC42	5	84.0×	6e-08
ADP signalling through P2Y purinoceptor 1	6	80.6×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
in utero embryonic development	6	10.3×	2e-03
G protein-coupled receptor signaling pathway	10	8.6×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2369 predictions. Top by Δscore:

Variant	Effect	Δscore
7:2731749:TT:T	acceptor_gain	1.0000
7:2733445:A:AC	donor_gain	1.0000
7:2733446:C:CC	donor_gain	1.0000
7:2733450:CCAG:C	donor_gain	1.0000
7:2794922:A:AC	donor_gain	1.0000
7:2794923:C:CT	donor_gain	1.0000
7:2794923:CT:C	donor_gain	1.0000
7:2794923:CTCA:C	donor_gain	1.0000
7:2794924:TCACC:T	donor_loss	1.0000
7:2794925:C:CC	donor_loss	1.0000
7:2794926:A:AC	donor_gain	1.0000
7:2794926:A:C	donor_loss	1.0000
7:2794927:C:CC	donor_gain	1.0000
7:2794927:CCAG:C	donor_gain	1.0000
7:2795139:GAGCC:G	acceptor_gain	1.0000
7:2795140:AGCC:A	acceptor_gain	1.0000
7:2795140:AGCCC:A	acceptor_gain	1.0000
7:2795141:GCC:G	acceptor_gain	1.0000
7:2795141:GCCCT:G	acceptor_gain	1.0000
7:2795142:CC:C	acceptor_gain	1.0000
7:2795142:CCC:C	acceptor_gain	1.0000
7:2795143:CC:C	acceptor_gain	1.0000
7:2795143:CCTA:C	acceptor_loss	1.0000
7:2795144:C:CC	acceptor_gain	1.0000
7:2796357:T:A	donor_gain	1.0000
7:2796380:A:AC	donor_gain	1.0000
7:2843850:CACCT:C	donor_loss	1.0000
7:2843851:A:AC	donor_loss	1.0000
7:2843852:CC:C	donor_loss	1.0000
7:2731746:TAATT:T	acceptor_gain	0.9900

AlphaMissense

2540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:2731615:A:G	W238R	1.000
7:2731615:A:T	W238R	1.000
7:2843953:T:A	K70M	1.000
7:2843956:C:T	G69D	1.000
7:2731436:C:A	K297N	0.999
7:2731436:C:G	K297N	0.999
7:2731437:T:A	K297M	0.999
7:2731439:G:C	N296K	0.999
7:2731439:G:T	N296K	0.999
7:2731577:G:C	F250L	0.999
7:2731577:G:T	F250L	0.999
7:2731578:A:G	F250S	0.999
7:2731579:A:G	F250L	0.999
7:2731601:G:C	F242L	0.999
7:2731601:G:T	F242L	0.999
7:2731603:A:G	F242L	0.999
7:2731613:C:A	W238C	0.999
7:2731613:C:G	W238C	0.999
7:2731624:G:T	R235S	0.999
7:2731634:C:A	Q231H	0.999
7:2731634:C:G	Q231H	0.999
7:2731638:C:T	G230D	0.999
7:2731639:C:G	G230R	0.999
7:2731641:C:T	G229D	0.999
7:2731646:A:C	D227E	0.999
7:2731646:A:T	D227E	0.999
7:2731647:T:C	D227G	0.999
7:2731647:T:G	D227A	0.999
7:2731648:C:G	D227H	0.999
7:2731648:C:T	D227N	0.999

dbSNP variants (sampled 300 via entrez): RS1000020775 (7:2785718 A>T), RS1000044845 (7:2844593 C>T), RS1000052206 (7:2741217 G>A,T), RS1000060664 (7:2756768 C>A,T), RS1000070205 (7:2755648 A>C), RS1000070860 (7:2812004 C>T), RS1000144046 (7:2812162 T>C), RS1000163411 (7:2772317 T>C), RS1000193055 (7:2752681 G>A), RS1000214838 (7:2776629 G>A,T), RS1000220106 (7:2735292 A>G), RS1000232138 (7:2780960 C>T), RS1000284978 (7:2837223 G>C,T), RS1000321872 (7:2748375 T>C), RS1000339111 (7:2837406 G>C,T)

Disease associations

OMIM: gene MIM:604394 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

95 associations (top):

Study	Trait	p-value
GCST000175_2	Height	7.000000e-15
GCST000372_3	Height	3.000000e-09
GCST000611_23	Height	7.000000e-07
GCST000817_171	Height	2.000000e-33
GCST000964_10	Ulcerative colitis	3.000000e-15
GCST001728_9	Ulcerative colitis	6.000000e-17
GCST001760_3	White matter integrity	5.000000e-06
GCST002647_64	Height	2.000000e-71
GCST002702_58	Height	4.000000e-27
GCST003518_48	Daytime sleep phenotypes	5.000000e-06
GCST003772_10	Loneliness (linear analysis)	7.000000e-06
GCST003995_15	Tonsillectomy	3.000000e-11
GCST004063_39	Waist circumference adjusted for body mass index	3.000000e-11
GCST004063_72	Waist circumference adjusted for body mass index	1.000000e-10
GCST004066_37	Hip circumference	9.000000e-06
GCST004066_90	Hip circumference	2.000000e-08
GCST004067_112	Hip circumference adjusted for BMI	4.000000e-20
GCST004067_150	Hip circumference adjusted for BMI	7.000000e-13
GCST004067_43	Hip circumference adjusted for BMI	1.000000e-10
GCST004131_74	Inflammatory bowel disease	2.000000e-07
GCST004133_52	Ulcerative colitis	4.000000e-11
GCST004500_12	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-07
GCST004501_51	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	1.000000e-06
GCST004501_52	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	6.000000e-06
GCST004504_50	Waist circumference adjusted for BMI in non-smokers	3.000000e-06
GCST004603_35	Platelet count	2.000000e-15
GCST004607_152	Plateletcrit	3.000000e-14
GCST004625_93	Monocyte count	3.000000e-09
GCST005014_6	Tonsillectomy	3.000000e-11
GCST005146_35	Birth weight	5.000000e-09

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004641	white matter integrity
EFO:0007828	daytime rest measurement
EFO:0007865	loneliness measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0005091	monocyte count
EFO:0004344	birth weight
EFO:0008487	lateral ventricle volume measurement
EFO:0004341	body fat distribution
EFO:0004338	body weight
EFO:0005939	parental genotype effect measurement
EFO:0004346	neuroimaging measurement
EFO:0006935	thalamus volume
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement
EFO:0004980	appendicular lean mass
EFO:0004842	eosinophil count
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3308913 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
Estradiol	affects cotreatment, increases expression, affects binding, increases reaction	3
Acetaminophen	increases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	increases methylation	1
Sunitinib	increases expression	1
Glyphosate	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	affects methylation	1
Benztropine	affects cotreatment, decreases expression	1
Carbamazepine	affects expression	1
Chelating Agents	affects binding, increases expression	1
Clozapine	increases expression	1
Copper	affects binding, increases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1072741	Binding	Inhibition of Galpha-12-stimulated serum response factor-luciferase expression in human PC3 cells at 10 uM by Matrigel cell invasion assay	Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7QP	Ubigene A-549 GNA12 KO	Cancer cell line	Male
CVCL_D9FJ	Ubigene HEK293 GNA12 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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