RGS12

Summary

RGS12 (regulator of G protein signaling 12, HGNC:9994) is a protein-coding gene on chromosome 4p16.3, encoding Regulator of G-protein signaling 12 (O14924). Regulates G protein-coupled receptor signaling cascades.

This gene encodes a member of the ‘regulator of G protein signaling’ (RGS) gene family. The encoded protein may function as a guanosine triphosphatase (GTPase)-activating protein as well as a transcriptional repressor. This protein may play a role in tumorigenesis. Multiple transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their biological nature has not been determined.

Source: NCBI Gene 6002 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 273 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001394154

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9994
Approved symbol	RGS12
Name	regulator of G protein signaling 12
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159788
Ensembl biotype	protein_coding
OMIM	602512
Entrez	6002

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 11 protein_coding_CDS_not_defined, 9 retained_intron, 6 protein_coding, 1 nonsense_mediated_decay

ENST00000336727, ENST00000338806, ENST00000344733, ENST00000382788, ENST00000502947, ENST00000503041, ENST00000504194, ENST00000504559, ENST00000505570, ENST00000506631, ENST00000506998, ENST00000507041, ENST00000507246, ENST00000508158, ENST00000509746, ENST00000509772, ENST00000510803, ENST00000511709, ENST00000511805, ENST00000512266, ENST00000512990, ENST00000513784, ENST00000513991, ENST00000514268, ENST00000515521, ENST00000643191, ENST00000864047

RefSeq mRNA: 11 — MANE Select: NM_001394154 NM_001394154, NM_001394155, NM_001394156, NM_001394157, NM_001394158, NM_001394161, NM_001394162, NM_001394163, NM_002926, NM_198227, NM_198229

CCDS: CCDS3366, CCDS3367, CCDS3368

Canonical transcript exons

ENST00000336727 — 18 exons

Exon	Start	End
ENSE00001425932	3316070	3318051
ENSE00003470279	3416913	3417092
ENSE00003482744	3428090	3428169
ENSE00003527198	3342937	3343053
ENSE00003541097	3420642	3420718
ENSE00003575392	3422376	3422570
ENSE00003584624	3415978	3416121
ENSE00003600548	3430407	3430955
ENSE00003613169	3423515	3423641
ENSE00003629501	3422905	3422978
ENSE00003635352	3428558	3428711
ENSE00003649697	3414752	3414844
ENSE00003655152	3425464	3425560
ENSE00003670829	3386416	3386437
ENSE00003674786	3414072	3414241
ENSE00003680789	3417388	3417541
ENSE00003749906	3439455	3439913
ENSE00003934496	3293021	3293099

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0213 / max 293.6229, expressed in 1731 samples.

FANTOM5 promoters (25 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46682	6.8776	1638
46691	1.8894	535
46704	1.4682	241
46699	0.9628	237
46692	0.3205	183
46689	0.1959	79
46703	0.1409	70
46705	0.1285	65
46700	0.1274	72
46690	0.1270	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	96.64	gold quality
ventricular zone	UBERON:0003053	96.25	gold quality
cortical plate	UBERON:0005343	95.63	gold quality
esophagus mucosa	UBERON:0002469	95.53	gold quality
skin of leg	UBERON:0001511	94.91	gold quality
lower esophagus mucosa	UBERON:0035834	94.81	gold quality
right uterine tube	UBERON:0001302	94.78	gold quality
skin of abdomen	UBERON:0001416	94.62	gold quality
right frontal lobe	UBERON:0002810	94.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.04	gold quality
cerebellar hemisphere	UBERON:0002245	93.55	gold quality
prefrontal cortex	UBERON:0000451	93.32	gold quality
cerebellar cortex	UBERON:0002129	93.32	gold quality
ectocervix	UBERON:0012249	93.28	gold quality
cingulate cortex	UBERON:0003027	92.72	gold quality
anterior cingulate cortex	UBERON:0009835	92.64	gold quality
vagina	UBERON:0000996	92.59	gold quality
right lobe of liver	UBERON:0001114	92.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.54	gold quality
nucleus accumbens	UBERON:0001882	92.19	gold quality
mucosa of stomach	UBERON:0001199	92.15	gold quality
putamen	UBERON:0001874	92.06	gold quality
endocervix	UBERON:0000458	91.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.96	gold quality
esophagus	UBERON:0001043	91.83	gold quality
amygdala	UBERON:0001876	91.82	gold quality
gingival epithelium	UBERON:0001949	91.79	gold quality
caudate nucleus	UBERON:0001873	91.72	gold quality
zone of skin	UBERON:0000014	91.71	gold quality
metanephros cortex	UBERON:0010533	91.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	1000.92
E-HCAD-30	yes	756.09
E-ANND-3	yes	9.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting RGS12, 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-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-198	98.70	67.32	920
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-219B-5P	97.91	65.80	531
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-4793-5P	96.88	65.90	872

Literature-anchored findings (GeneRIF, showing 10)

• RGS12 is essential for the terminal differentiation of osteoclasts induced by RANKL. (PMID:17042716)
• Data support the notion that the Galpha, but not Gbetagamma, arm of the Gi/o signalling is involved in TRPC4 activation and unveil new roles for RGS and RGS12 in fine-tuning TRPC4 activities. (PMID:26987813)
• Findings identify RGS12 as a candidate tumor-suppressor gene in AA prostate cancer, which acts by decreasing expression of AKT and MNX1, establishing a novel oncogenic axis in this disparate disease setting. (PMID:28611045)
• RGS12 Represses Oral Cancer via the Phosphorylation and SUMOylation of PTEN. (PMID:33198557)
• RGS12 is a novel tumor suppressor in osteosarcoma that inhibits YAP-TEAD1-Ezrin signaling. (PMID:33686240)
• RGS12 Drives Macrophage Activation and Osteoclastogenesis in Periodontitis. (PMID:34796776)
• RGS12 inhibits the progression and metastasis of multiple myeloma by driving M1 macrophage polarization and activation in the bone marrow microenvironment. (PMID:34931491)
• RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling. (PMID:36797232)
• Distinct and overlapping RGS14 and RGS12 actions regulate NPT2A-mediated phosphate transport. (PMID:39293332)
• shows chromosomal mapping information for human locus. (PMID:9168931)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rgs12	ENSMUSG00000029101
rattus_norvegicus	Rgs12	ENSRNOG00000030568

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGSL1 (ENSG00000121446), RGS13 (ENSG00000127074), RGS22 (ENSG00000132554), RGS8 (ENSG00000135824), RGS3 (ENSG00000138835), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 12 — O14924 (reviewed: O14924)

All UniProt accessions (3): O14924, A0A2R8YCJ1, E9PBG5

UniProt curated annotations — full annotation on UniProt →

Function. Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Behaves as a cell cycle-dependent transcriptional repressor, promoting inhibition of S-phase DNA synthesis.

Subunit / interactions. Interacts with GNAI1. Interacts with GNAI2 and GNAI3; the interactions are GDP-dependent.

Subcellular location. Nucleus. Cytoplasm. Cell projection. Dendrite. Synapse Nucleus matrix.

Tissue specificity. Isoform 3 is brain specific.

Domain organisation. The GoLoco domain is necessary for interaction with GNAI1, GNAI2 and GNAI3.

Isoforms (7)

UniProt ID	Names	Canonical?
O14924-1	1, RGS12TS-L, TS, trans-spliced	yes
O14924-2	2, P, peripheral
O14924-3	3, B, brain
O14924-4	4
O14924-5	5, RGS12TS-S
O14924-6	6
O14924-7	7

RefSeq proteins (11): NP_001381083, NP_001381084, NP_001381085, NP_001381086, NP_001381087, NP_001381090, NP_001381091, NP_001381092, NP_002917, NP_937870, NP_937872 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR003109	GoLoco_motif	Conserved_site
IPR003116	RBD_dom	Domain
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016137	RGS	Domain
IPR024066	RGS_subdom1/3	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR036305	RGS_sf	Homologous_superfamily
IPR037880	RGS12_RGS	Domain
IPR044926	RGS_subdomain_2	Homologous_superfamily
IPR046995	RGS10/12/14-like	Family

Pfam: PF00595, PF00615, PF02188, PF02196, PF16611, PF16612, PF16613

UniProt features (67 total): compositionally biased region 11, helix 11, splice variant 10, modified residue 9, region of interest 7, domain 6, strand 5, sequence variant 3, turn 2, chain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2EBZ	SOLUTION NMR
2KV8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14924-F1	54.36	0.13

Functional residue map

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

Post-translational modifications (10): 172, 195, 524, 633, 661, 671, 850, 879, 943, 196

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 161 (showing top): NKX25_02, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, LHX3_01, CHX10_01, CAGCTG_AP4_Q5, PAX8_B, GATA3_01, BLALOCK_ALZHEIMERS_DISEASE_UP, GROSS_HYPOXIA_VIA_ELK3_UP, WTGAAAT_UNKNOWN, chr4p16, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOCC_NEURON_PROJECTION

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), regulation of G protein-coupled receptor signaling pathway (GO:0008277), negative regulation of signal transduction (GO:0009968), signal transduction (GO:0007165)

GO Molecular Function (4): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), GTPase regulator activity (GO:0030695), protein binding (GO:0005515)

GO Cellular Component (11): condensed nuclear chromosome (GO:0000794), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear matrix (GO:0016363), dendrite (GO:0030425), synapse (GO:0045202), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
nuclear lumen	3
signal transduction	2
regulation of signal transduction	2
GTPase activity	2
G protein-coupled receptor activity	1
G protein-coupled receptor signaling pathway	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
enzyme activator activity	1
GTPase regulator activity	1
nucleoside-triphosphatase regulator activity	1
binding	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
cell junction	1

Protein interactions and networks

STRING

1264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS12	GNB5	O14775	876
RGS12	SUCLG2	Q96I99	863
RGS12	ARHGEF1	Q92888	788
RGS12	ARHGEF11	O15085	775
RGS12	GNAQ	P50148	769
RGS12	GRK2	P25098	758
RGS12	RGSL1	A5PLK6	758
RGS12	CXCR2	P25025	746
RGS12	RGS7BP	Q6MZT1	720
RGS12	GNA13	Q14344	707
RGS12	SUCLG1	P53597	705
RGS12	MCF2	P10911	694
RGS12	GNAO1	P09471	690
RGS12	PLEK	P08567	686
RGS12	TAMALIN	Q7Z6J2	683

IntAct

188 interactions, top by confidence:

A	B	Type	Score
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAE	RGS12	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
RGS12	PM20D2	psi-mi:“MI:0915”(physical association)	0.560
GNAI1	GNAT3	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
RGS12	E6	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD4	RGS12	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
HTRA1	RGS12	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
RGS12	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (58): RGS12 (Affinity Capture-MS), RGS12 (Affinity Capture-MS), RGS12 (Affinity Capture-MS), RGS12 (Affinity Capture-MS), RGS12 (Affinity Capture-MS), RGS12 (Two-hybrid), RGS12 (Proximity Label-MS), RGS12 (Affinity Capture-RNA), RGS12 (Affinity Capture-MS), RGS12 (Proximity Label-MS), RGS12 (Two-hybrid), RGS12 (Affinity Capture-MS), RGS12 (Affinity Capture-MS), RGS12 (Affinity Capture-MS), RGS12 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JUG7, A1L390, E9Q0S6, O08774, O14924, O15085, O43182, O54834, O54960, O60307, O75052, P57095, Q13009, Q3U1V8, Q3U214, Q3UHC7, Q4VAC9, Q5DU25, Q5JU85, Q5RBI7, Q5SXA9, Q5VWQ8, Q60610, Q64512, Q6AX33, Q6DN90, Q6NXJ0, Q6P0Q8, Q6P1I6, Q6ZMN7, Q76G19, Q76LL6, Q76M68, Q7T2V3, Q810W7, Q8CGE9, Q8IX03, Q8R0S2, Q8R4H2, Q8WYP3

Diamond homologs: A1A643, F1S668, O08773, O08774, O08849, O08850, O08899, O14921, O14924, O15169, O15492, O15539, O35625, O42400, O43566, O43665, O46469, O46470, O46471, O54828, O54829, O70239, O70240, O70521, O75916, O76081, O88566, O94810, P34295, P41220, P49758, P49795, P49796, P49797, P49798, P49799, P49800, P49802, P49803, P49804

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
Activation of BAD and translocation to mitochondria	7	64.2×	7e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	56.6×	1e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	56.6×	1e-09
Activation of BH3-only proteins	7	41.9×	8e-09
RHO GTPases activate PKNs	8	30.6×	7e-09
Dopamine Neurotransmitter Release Cycle	5	29.9×	1e-05
Assembly and cell surface presentation of NMDA receptors	9	27.5×	2e-09
Neurexins and neuroligins	11	26.1×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	48.8×	3e-12
protein localization to synapse	6	38.6×	2e-06
receptor clustering	6	31.5×	4e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	29.2×	1e-06
protein targeting	7	21.6×	4e-06
intracellular protein localization	10	8.8×	2e-05
protein-containing complex assembly	9	8.6×	9e-05
regulation of small GTPase mediated signal transduction	7	8.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	238
Likely benign	17
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4408 predictions. Top by Δscore:

Variant	Effect	Δscore
4:3316068:AG:A	acceptor_gain	1.0000
4:3316069:GG:G	acceptor_gain	1.0000
4:3342931:GTTTA:G	acceptor_loss	1.0000
4:3342932:TTTA:T	acceptor_loss	1.0000
4:3342933:TTAG:T	acceptor_loss	1.0000
4:3342934:TAGG:T	acceptor_loss	1.0000
4:3342935:A:G	acceptor_loss	1.0000
4:3342935:AG:A	acceptor_gain	1.0000
4:3342936:GG:G	acceptor_gain	1.0000
4:3343049:TTGAG:T	donor_loss	1.0000
4:3343050:TGAG:T	donor_loss	1.0000
4:3343051:GAGG:G	donor_loss	1.0000
4:3343052:AGGT:A	donor_loss	1.0000
4:3343053:GGTAA:G	donor_loss	1.0000
4:3343054:G:T	donor_loss	1.0000
4:3343055:T:A	donor_loss	1.0000
4:3386414:A:AG	acceptor_gain	1.0000
4:3386415:G:GA	acceptor_gain	1.0000
4:3386415:GT:G	acceptor_gain	1.0000
4:3414242:G:GG	donor_gain	1.0000
4:3414747:CTTA:C	acceptor_loss	1.0000
4:3414750:A:AG	acceptor_gain	1.0000
4:3414750:A:T	acceptor_loss	1.0000
4:3414750:AG:A	acceptor_gain	1.0000
4:3414751:G:GC	acceptor_gain	1.0000
4:3414751:GG:G	acceptor_gain	1.0000
4:3414751:GGA:G	acceptor_gain	1.0000
4:3414751:GGAT:G	acceptor_gain	1.0000
4:3414751:GGATT:G	acceptor_gain	1.0000
4:3414840:AGGAG:A	donor_gain	1.0000

AlphaMissense

9491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:3414185:T:A	W712R	1.000
4:3414185:T:C	W712R	1.000
4:3414207:T:C	L719P	1.000
4:3414755:T:C	F732L	1.000
4:3414757:T:A	F732L	1.000
4:3414757:T:G	F732L	1.000
4:3414759:T:C	L733P	1.000
4:3414770:T:C	F737L	1.000
4:3414772:C:A	F737L	1.000
4:3414772:C:G	F737L	1.000
4:3416923:T:C	L813P	1.000
4:3416950:T:C	F822S	1.000
4:3316271:T:C	F34S	0.999
4:3316361:T:A	I64K	0.999
4:3316870:T:G	Y234D	0.999
4:3317018:T:C	L283P	0.999
4:3317050:T:G	Y294D	0.999
4:3317066:T:C	L299P	0.999
4:3317108:G:A	G313E	0.999
4:3317111:T:C	L314S	0.999
4:3317114:T:A	V315D	0.999
4:3317179:T:C	C337R	0.999
4:3317189:T:C	F340S	0.999
4:3317257:T:C	C363R	0.999
4:3317284:T:C	C372R	0.999
4:3317294:T:C	F375S	0.999
4:3317440:A:C	S424R	0.999
4:3317442:C:A	S424R	0.999
4:3317442:C:G	S424R	0.999
4:3414187:G:C	W712C	0.999

dbSNP variants (sampled 300 via entrez): RS1000001665 (4:3381267 A>G), RS1000039517 (4:3313631 C>T), RS1000049963 (4:3440260 G>A,C), RS1000072340 (4:3373378 G>A,C,T), RS1000080970 (4:3421854 C>T), RS1000088140 (4:3305145 T>C), RS1000089874 (4:3382355 C>T), RS1000111519 (4:3286841 C>A,T), RS1000153225 (4:3306825 C>T), RS1000175230 (4:3435348 T>A), RS1000195110 (4:3323253 A>G), RS1000197674 (4:3336827 A>C), RS1000204936 (4:3307996 C>A,T), RS1000209911 (4:3366449 C>T), RS1000237418 (4:3341034 C>G,T)

Disease associations

OMIM: gene MIM:602512 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST004865_74	Itch intensity from mosquito bite adjusted by bite size	8.000000e-06
GCST004923_3	Tuberculosis	3.000000e-08
GCST005196_114	Coronary artery disease	4.000000e-08
GCST005984_11	Glomerular filtration rate	2.000000e-09
GCST005985_65	Creatinine levels	9.000000e-11
GCST005988_2	Serum albumin levels	2.000000e-22
GCST005991_78	Platelet count	5.000000e-11
GCST006034_32	Total cholesterol levels	3.000000e-08
GCST006946_30	Worry too long after an embarrassing experience	3.000000e-08
GCST007344_120	Estimated glomerular filtration rate	1.000000e-08
GCST007876_15	Estimated glomerular filtration rate	4.000000e-11
GCST007930_76	Medication use (agents acting on the renin-angiotensin system)	3.000000e-08
GCST007931_20	Medication use (HMG CoA reductase inhibitors)	1.000000e-09
GCST010461_2	Hepatocyte growth factor levels	2.000000e-09
GCST010988_224	Adult body size	8.000000e-12
GCST011346_17	Total cholesterol levels	2.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004309	platelet count
EFO:0004574	total cholesterol measurement
EFO:0009589	worry measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1293276 (SINGLE PROTEIN), CHEMBL3885584 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 179,787 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1590	PSEUDOEPHEDRINE	4	25,626
CHEMBL273575	NOMIFENSINE	4	7,327
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL1255653	SEPIAPTERIN	3	676
CHEMBL51085	EBSELEN	3	13,237
CHEMBL417799	SANGUINARIUM	2	8,822
CHEMBL593429	ALLANTOIN	2	69,429
CHEMBL19215	METERGOLINE	2	2,927

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — R12 family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
Z55627844	Inhibition	4.66	pIC50

ChEMBL bioactivities

65 potent at pChembl≥5 of 152 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	Potency	20	nM	CHEMBL1515691
6.25	Potency	562.3	nM	CHEMBL1359410
6.10	Potency	794.3	nM	CHEMBL338790
6.00	Potency	1000	nM	CHEMBL1356536
5.80	Potency	1585	nM	CHEMBL1477127
5.80	Potency	1585	nM	CHEMBL605003
5.75	Potency	1778	nM	CHEMBL1502753
5.70	Potency	1995	nM	LAVENDUSTIN C
5.70	Potency	1995	nM	CHEMBL1475433
5.65	Potency	2239	nM	CHEMBL1437992
5.65	Potency	2239	nM	CHEMBL1504634
5.60	Potency	2512	nM	CHEMBL1559351
5.60	Potency	2512	nM	CHEMBL1600326
5.60	Potency	2512	nM	TYRPHOSTIN 25
5.60	Potency	2512	nM	CHEMBL105739
5.55	Potency	2818	nM	DIOTYROSINE
5.55	Potency	2818	nM	CHEMBL1417798
5.50	Potency	3162	nM	CHEMBL1499859
5.50	Potency	3162	nM	SB-216763
5.45	Potency	3548	nM	CHEMBL1375635
5.45	Potency	3548	nM	CHEMBL1494852
5.40	Potency	3981	nM	CHEMBL1336264
5.40	Potency	3981	nM	CHEMBL1510394
5.40	Potency	3981	nM	TYRPHOSTIN A9
5.40	Potency	3981	nM	CHEMBL1363013
5.40	Potency	3981	nM	GW282974X
5.40	Potency	3981	nM	CHEMBL1591830
5.35	Potency	4467	nM	CHEMBL1438881
5.35	Potency	4467	nM	CHEMBL1611372
5.35	Potency	4467	nM	CHEMBL1497017
5.30	Potency	5012	nM	CHEMBL1514486
5.30	Potency	5012	nM	CHEMBL548062
5.30	Potency	5012	nM	CHEMBL1448859
5.30	Potency	5012	nM	CHEMBL1316080
5.25	Potency	5623	nM	CHEMBL3195374
5.20	Potency	6310	nM	CHEMBL1409483
5.20	Potency	6310	nM	DEPHOSTATIN
5.20	Potency	6310	nM	CHEMBL397209
5.20	Potency	6310	nM	CHEMBL1222317
5.15	Potency	7080	nM	CHEMBL1422235
5.15	Potency	7080	nM	CHEMBL3207913
5.15	Potency	7080	nM	CHEMBL1503187
5.15	Potency	7080	nM	CHEMBL1306714
5.10	Potency	7943	nM	CHEMBL3208316
5.10	Potency	7943	nM	CHEMBL2374259
5.10	Potency	7943	nM	CHEMBL1324890
5.10	Potency	7943	nM	CHEMBL1392987
5.10	Potency	7943	nM	CHEMBL72365
5.10	Potency	7943	nM	PSEUDOEPHEDRINE
5.05	Potency	8912	nM	CHEMBL1450086

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
methylparaben	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
beta-methylcholine	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	decreases expression	1
bisphenol S	affects methylation, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Decitabine	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation, affects methylation, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	increases methylation	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Methapyrilene	affects methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613902	Functional	PUBCHEM_BIOASSAY: Confirmation qHTS Assay for Inhibitors of RGS12 GoLoco Motif Activity (Red Fluorophore). (Class of assay: confirmatory) [Related pubchem assays: 880 (qHTS Assay for Inhibitors of RGS12 GoLoco Motif Activity (Red Fluorophor	PubChem BioAssay data set

Clinical trials (associated diseases)

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