RGS3

Summary

RGS3 (regulator of G protein signaling 3, HGNC:9999) is a protein-coding gene on chromosome 9q32, encoding Regulator of G-protein signaling 3 (P49796). Down-regulates signaling from heterotrimeric G-proteins by increasing the GTPase activity of the alpha subunits, thereby driving them into their inactive GDP-bound form.

This gene encodes a member of the regulator of G-protein signaling (RGS) family. This protein is a GTPase-activating protein that inhibits G-protein-mediated signal transduction. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. Long isoforms are largely cytosolic and plasma membrane-associated with a function in Wnt signaling and in the epithelial mesenchymal transition, while shorter N-terminally-truncated isoforms can be nuclear.

Source: NCBI Gene 5998 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 235 total
• MANE Select transcript: NM_001394167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9999
Approved symbol	RGS3
Name	regulator of G protein signaling 3
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	C2PA, FLJ20370, PDZ-RGS3
Ensembl gene	ENSG00000138835
Ensembl biotype	protein_coding
OMIM	602189
Entrez	5998

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 14 protein_coding, 9 protein_coding_CDS_not_defined, 8 retained_intron

ENST00000317613, ENST00000342620, ENST00000343817, ENST00000350696, ENST00000374134, ENST00000374136, ENST00000374140, ENST00000394646, ENST00000460000, ENST00000462143, ENST00000463806, ENST00000464306, ENST00000466314, ENST00000466735, ENST00000467805, ENST00000470775, ENST00000471324, ENST00000478599, ENST00000485822, ENST00000487344, ENST00000488259, ENST00000488620, ENST00000489082, ENST00000490241, ENST00000492676, ENST00000496113, ENST00000496264, ENST00000496275, ENST00000497435, ENST00000620489, ENST00000695401

RefSeq mRNA: 14 — MANE Select: NM_001394167 NM_001276260, NM_001276261, NM_001276262, NM_001282922, NM_001282923, NM_001322214, NM_001322215, NM_001351526, NM_001394167, NM_017790, NM_130795, NM_134427, NM_144488, NM_144489

CCDS: CCDS35113, CCDS35114, CCDS65111, CCDS6797, CCDS6798, CCDS94464

Canonical transcript exons

ENST00000695401 — 23 exons

Exon	Start	End
ENSE00001941941	113463727	113463881
ENSE00003467124	113505442	113505523
ENSE00003486454	113497314	113497404
ENSE00003501609	113485625	113485693
ENSE00003542863	113517541	113517624
ENSE00003550113	113595599	113595765
ENSE00003551077	113495786	113495846
ENSE00003551315	113484138	113484232
ENSE00003561947	113594430	113594531
ENSE00003570786	113596768	113597738
ENSE00003582226	113479491	113479541
ENSE00003619965	113498025	113498080
ENSE00003625037	113508541	113508580
ENSE00003634414	113507287	113507638
ENSE00003638481	113522930	113523041
ENSE00003651261	113483059	113483117
ENSE00003651834	113506388	113506493
ENSE00003660133	113536796	113536918
ENSE00003664373	113514458	113514654
ENSE00003685672	113529221	113529264
ENSE00003692726	113591333	113591397
ENSE00003757219	113583450	113584427
ENSE00003789640	113594919	113594980

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.6131 / max 342.0064, expressed in 1717 samples.

FANTOM5 promoters (27 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98125	26.4338	1269
98097	1.7957	500
98124	1.5104	485
98100	1.4667	263
98104	1.1752	142
98120	1.0328	430
98119	0.9861	537
98121	0.7904	279
98098	0.7468	265
98118	0.7215	467

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.91	gold quality
cartilage tissue	UBERON:0002418	97.49	gold quality
periodontal ligament	UBERON:0008266	97.34	gold quality
ascending aorta	UBERON:0001496	97.27	gold quality
thoracic aorta	UBERON:0001515	97.22	gold quality
descending thoracic aorta	UBERON:0002345	96.70	gold quality
heart left ventricle	UBERON:0002084	96.11	gold quality
gall bladder	UBERON:0002110	96.04	gold quality
cardiac ventricle	UBERON:0002082	95.99	gold quality
right atrium auricular region	UBERON:0006631	95.95	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.80	gold quality
granulocyte	CL:0000094	95.69	gold quality
cardiac atrium	UBERON:0002081	95.64	gold quality
heart	UBERON:0000948	95.44	gold quality
aorta	UBERON:0000947	95.31	gold quality
triceps brachii	UBERON:0001509	94.78	gold quality
omental fat pad	UBERON:0010414	94.45	gold quality
peritoneum	UBERON:0002358	94.40	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.27	gold quality
left coronary artery	UBERON:0001626	94.16	gold quality
right coronary artery	UBERON:0001625	94.10	gold quality
saphenous vein	UBERON:0007318	94.10	gold quality
coronary artery	UBERON:0001621	94.05	gold quality
popliteal artery	UBERON:0002250	93.93	gold quality
tibial artery	UBERON:0007610	93.92	gold quality
tibia	UBERON:0000979	93.84	gold quality
upper lobe of left lung	UBERON:0008952	93.81	gold quality
adult mammalian kidney	UBERON:0000082	93.68	gold quality
mucosa of stomach	UBERON:0001199	93.64	gold quality
metanephros cortex	UBERON:0010533	93.60	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	16.46
E-MTAB-4850	no	215.59
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting RGS3, 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-5193	100.00	67.26	1744
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-5681B	94.82	69.30	514
HSA-MIR-7108-3P	94.37	64.79	183
HSA-MIR-181A-3P	90.53	67.01	77

Literature-anchored findings (GeneRIF, showing 23)

• Data are consistent with the model wherein 14-3-3 serves as a scavenger of RGS3, regulating the amounts of RGS3 available for binding G-proteins. (PMID:11985497)
• C2PA is expressed in the cell nucleus and induces heat shock response element (HSE)-dependent gene transcription (PMID:12210723)
• RFS3 promoted the conversion of more stable Ca2+ elevations into oscillatory signals. (PMID:15383626)
• mRNA expression of CCT5, RGS3, and YKT6 was significantly up-regulated in p53-mutated tumors and associated with a low response rate to docetaxel. (PMID:16821082)
• Full-length RGS3, RGS3T, and the core domain of RGS3 were equally effective in antagonizing inhibition of Ca(V)2.3 through M(2)R. (PMID:16855219)
• RGS3L functions as a molecular switch, redirecting Gi-coupled receptors via Gbetagamma-dimers and PI3K from Rac1 to RhoA activation. (PMID:17300916)
• This study identifies a novel, noncanonical role of RGS3 in regulation of TGF-beta signaling through its interaction with Smads and interfering with Smad heteromerization. (PMID:18287247)
• in apoptosis-initiated cells, the ligand-dependent C5aR-mediated dual signal affects the fate of cells, either apoptosis execution or survival, through regulation of RGS3 gene expression and subsequent modulation of ERK signal. (PMID:19333232)
• Regulator of G-protein signalling 3 (RGS3) showed a difference between follicular cells from follicles leading to a pregnancy or developmental failure. (PMID:19778949)
• 14-3-3 protein binding induces structural changes in both the N-terminal part and the C-terminal RGS domain of phosphorylated RGS3 molecule (PMID:20347994)
• Results suggest that the 14-3-3 protein binding affects the structure of the Galpha interaction portion of RGS3 as well as sterically blocks the interaction between the RGS domain and the Galpha subunit of heterotrimeric G proteins. (PMID:22027839)
• PDZ-RGS3 can enhance signals generated by the Wnt canonical pathway and plays a pivotal role in epithelial mesenchymal transition (PMID:22859293)
• ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. (PMID:24297163)
• cardiac overexpression of RGS3 inhibits maladaptive hypertrophy and fibrosis and improves cardiac function by blocking MEK-ERK1/2 signaling (PMID:24375609)
• Our data provide a novel miR-25/RGS3 signal in the development of lung cancer. (PMID:26416661)
• Findings suggest that overexpressed RGS3 regulated by microRNA-126 through the post-transcriptional modulation is associated significantly with a poor prognosis of GC patients. (PMID:27754994)
• It has been reported that mitotic kinesin KIF20A interacts with RGS3 and plays a crucial role in controlling the division modes of neural progenitor cells during cortical neurogenesis. (PMID:30006548)
• A Multi-Trait Approach Identified Genetic Variants Including a Rare Mutation in RGS3 with Impact on Abnormalities of Cardiac Structure/Function. (PMID:30971721)
• The present study revealed that miR1263p plays a role as a tumor suppressor in regulating TNBC cell activities by targeting RGS3. (PMID:31364749)
• Regulator of G-protein signalling 3 and its regulator microRNA-133a mediate cell proliferation in gastric cancer. (PMID:32928707)
• The G protein signaling regulator RGS3 enhances the GTPase activity of KRAS. (PMID:34618566)
• Pseudogene UBE2MP1 derived transcript enhances in vitro cell proliferation and apoptosis resistance of hepatocellular carcinoma cells through miR-145-5p/RGS3 axis. (PMID:36214767)
• RGS3 and IL1RAPL1 missense variants implicate defective neurotransmission in early-onset inherited schizophrenias. (PMID:36318984)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-154e10.1	ENSDARG00000094605
danio_rerio	rgs3a	ENSDARG00000099746
mus_musculus	Rgs3	ENSMUSG00000059810
rattus_norvegicus	Rgs3	ENSRNOG00000024501

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGSL1 (ENSG00000121446), RGS13 (ENSG00000127074), RGS22 (ENSG00000132554), RGS8 (ENSG00000135824), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 3 — P49796 (reviewed: P49796)

All UniProt accessions (8): P49796, A0A087WUY2, A0A8Q3WKG2, C9J582, C9J6G2, H7BXY1, H7C539, Q5VXC0

UniProt curated annotations — full annotation on UniProt →

Function. Down-regulates signaling from heterotrimeric G-proteins by increasing the GTPase activity of the alpha subunits, thereby driving them into their inactive GDP-bound form. Down-regulates G-protein-mediated release of inositol phosphates and activation of MAP kinases.

Subunit / interactions. Binds EFNB1 and EFNB2. Binds the GNB1-GNG2 heterodimer.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Post-translational modifications. Phosphorylated by cyclic GMP-dependent protein kinase. ISGylated.

Miscellaneous. Nuclear.

Isoforms (9)

UniProt ID	Names	Canonical?
P49796-3	3	yes
P49796-1	1
P49796-2	2, RGS3T
P49796-4	4, 1
P49796-5	5
P49796-6	6, C2PA-RGS3
P49796-7	7
P49796-8	8, RGS3S
P49796-9	9

RefSeq proteins (14): NP_001263189, NP_001263190, NP_001263191, NP_001269851, NP_001269852, NP_001309143, NP_001309144, NP_001338455, NP_001381096, NP_060260, NP_570613, NP_602299, NP_652759, NP_652760 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001478	PDZ	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016137	RGS	Domain
IPR024066	RGS_subdom1/3	Homologous_superfamily
IPR034951	RGS_RGS3	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR036305	RGS_sf	Homologous_superfamily
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00168, PF00595, PF00615

UniProt features (74 total): helix 15, strand 13, splice variant 12, sequence conflict 12, modified residue 6, compositionally biased region 5, domain 3, region of interest 3, sequence variant 2, turn 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3FBK	X-RAY DIFFRACTION	2
2OJ4	X-RAY DIFFRACTION	2.3
2F5Y	X-RAY DIFFRACTION	2.39

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49796-F1	55.90	0.22

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 (6): 448, 674, 943, 946, 978, 1007

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 0 (showing top):

GO Biological Process (3): 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)

GO Molecular Function (3): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
regulation of signal transduction	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
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS3	EFNB2	P52799	948
RGS3	EFNB1	P98172	908
RGS3	EFNB3	Q15768	878
RGS3	GNAQ	P50148	653
RGS3	C5orf22	Q49AR2	537
RGS3	GIPC1	O14908	524
RGS3	CXCL12	P48061	515
RGS3	GPRASP1	Q5JY77	498
RGS3	GNA11	P29992	491
RGS3	SMAD2	Q15796	447
RGS3	RIMS1	Q86UR5	433
RGS3	NCK2	O43639	431
RGS3	ADRB3	P13945	428
RGS3	RGS12	O14924	420
RGS3	CIMAP1A	Q96PU9	418

IntAct

33 interactions, top by confidence:

A	B	Type	Score
PLSCR1	RGS3	psi-mi:“MI:0915”(physical association)	0.560
RGS3	GORASP2	psi-mi:“MI:0915”(physical association)	0.550
GORASP2	RGS3	psi-mi:“MI:0915”(physical association)	0.550
RGS3	ZNF24	psi-mi:“MI:0914”(association)	0.530
YWHAZ	RGS3	psi-mi:“MI:0914”(association)	0.530
RGS3	YWHAZ	psi-mi:“MI:0914”(association)	0.530
ACD	RGS3	psi-mi:“MI:0915”(physical association)	0.510
RGS3	RPL7L1	psi-mi:“MI:0915”(physical association)	0.400
RGS3	HMGA1	psi-mi:“MI:0915”(physical association)	0.400
YWHAB	RGS3	psi-mi:“MI:0915”(physical association)	0.400
ARRB1		psi-mi:“MI:0914”(association)	0.350
CLK2	PRPF4	psi-mi:“MI:0914”(association)	0.350
RGS3	ZNF646	psi-mi:“MI:0914”(association)	0.350
RGS3	SKAP2	psi-mi:“MI:0914”(association)	0.350
IRF5	GTPBP1	psi-mi:“MI:0914”(association)	0.350
RGS3	FLOT1	psi-mi:“MI:0914”(association)	0.350
RGS3	YWHAQ	psi-mi:“MI:0914”(association)	0.350
ACD	RGS3	psi-mi:“MI:0915”(physical association)	0.000
HES4	RGS3	psi-mi:“MI:0915”(physical association)	0.000
isftu1	RGS3	psi-mi:“MI:0915”(physical association)	0.000
alsS	RGS3	psi-mi:“MI:0915”(physical association)	0.000
RGS3	deoB	psi-mi:“MI:0915”(physical association)	0.000
	RGS3	psi-mi:“MI:0915”(physical association)	0.000
RGS3	yscH	psi-mi:“MI:0915”(physical association)	0.000
yscP	RGS3	psi-mi:“MI:0915”(physical association)	0.000
yopM	RGS3	psi-mi:“MI:0915”(physical association)	0.000
RGS3		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (95): RGS3 (Two-hybrid), GORASP2 (Two-hybrid), RGS3 (Two-hybrid), CRAT (Affinity Capture-MS), UACA (Affinity Capture-MS), SKAP2 (Affinity Capture-MS), CEP72 (Affinity Capture-MS), RBAK (Affinity Capture-MS), EFNB2 (Affinity Capture-MS), ATG9A (Affinity Capture-MS), ZKSCAN8 (Affinity Capture-MS), ZNF24 (Affinity Capture-MS), REL (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), ZNF324B (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, A1A5B6, A4D2P6, D7PF45, F1LXF1, O15357, O60346, O75808, P11274, P49796, P52734, P53349, P59672, P70268, P78524, P98174, Q0QWG9, Q13233, Q13905, Q16825, Q3MII6, Q50H33, Q5RDA9, Q62925, Q63433, Q6NS60, Q6P549, Q6PDJ6, Q6WVG3, Q7Z5H3, Q8BL80, Q8BUP8, Q8N2R8, Q8TF61, Q8VHK2, Q8WXD9, Q924W7, Q92625, Q96CX2

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	180
Likely benign	14
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

6035 predictions. Top by Δscore:

Variant	Effect	Δscore
9:113462018:CAGGT:C	acceptor_loss	1.0000
9:113462019:A:AC	acceptor_loss	1.0000
9:113462199:CAGG:C	donor_loss	1.0000
9:113462201:GGTA:G	donor_loss	1.0000
9:113462203:T:G	donor_loss	1.0000
9:113483057:A:AG	acceptor_gain	1.0000
9:113483058:G:GG	acceptor_gain	1.0000
9:113484130:A:AG	acceptor_gain	1.0000
9:113484136:A:G	acceptor_gain	1.0000
9:113484233:G:GG	donor_gain	1.0000
9:113497401:AGAGG:A	donor_loss	1.0000
9:113497402:GAG:G	donor_gain	1.0000
9:113497402:GAGGT:G	donor_loss	1.0000
9:113497403:AG:A	donor_loss	1.0000
9:113497404:GG:G	donor_loss	1.0000
9:113497405:G:GA	donor_loss	1.0000
9:113497406:T:G	donor_loss	1.0000
9:113507639:G:GC	donor_loss	1.0000
9:113507640:T:A	donor_loss	1.0000
9:113508579:AGGTG:A	donor_loss	1.0000
9:113508580:GGTG:G	donor_loss	1.0000
9:113508581:G:T	donor_loss	1.0000
9:113508582:T:A	donor_loss	1.0000
9:113514456:A:AG	acceptor_gain	1.0000
9:113514457:G:GG	acceptor_gain	1.0000
9:113514597:C:G	donor_gain	1.0000
9:113514651:TCAG:T	donor_loss	1.0000
9:113514652:CAGG:C	donor_loss	1.0000
9:113514653:AG:A	donor_loss	1.0000
9:113514654:GG:G	donor_loss	1.0000

AlphaMissense

7080 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:113522955:T:C	L595P	1.000
9:113594944:T:A	W1070R	1.000
9:113594944:T:C	W1070R	1.000
9:113595622:T:C	F1090L	1.000
9:113595623:T:C	F1090S	1.000
9:113595624:C:A	F1090L	1.000
9:113595624:C:G	F1090L	1.000
9:113595626:T:C	L1091P	1.000
9:113595637:T:C	F1095L	1.000
9:113595638:T:C	F1095S	1.000
9:113595639:C:A	F1095L	1.000
9:113595639:C:G	F1095L	1.000
9:113595653:T:C	L1100P	1.000
9:113595658:T:C	F1102L	1.000
9:113595659:T:C	F1102S	1.000
9:113595660:C:A	F1102L	1.000
9:113595660:C:G	F1102L	1.000
9:113595661:T:A	W1103R	1.000
9:113595661:T:C	W1103R	1.000
9:113595719:C:A	A1122D	1.000
9:113596835:T:C	F1160S	1.000
9:113596865:T:C	L1170P	1.000
9:113596882:T:G	Y1176D	1.000
9:113596891:T:C	F1179L	1.000
9:113596892:T:C	F1179S	1.000
9:113596893:T:A	F1179L	1.000
9:113596893:T:G	F1179L	1.000
9:113505476:T:C	F311S	0.999
9:113505482:T:A	I313N	0.999
9:113505506:T:A	V321D	0.999

dbSNP variants (sampled 300 via entrez): RS1000022701 (9:113461905 C>T), RS1000073389 (9:113588204 G>A), RS1000109750 (9:113528911 G>A), RS1000110562 (9:113556991 A>G,T), RS1000147037 (9:113458931 T>C), RS1000149657 (9:113486525 G>A), RS1000176481 (9:113558559 G>A), RS1000200944 (9:113466749 T>C), RS1000208459 (9:113556901 G>C), RS1000224998 (9:113463081 T>G), RS1000226317 (9:113473287 TAGGTATAGAGAGGCTAAC>T), RS1000232188 (9:113557466 T>C), RS1000239287 (9:113563134 C>T), RS1000239441 (9:113557367 A>G), RS1000279616 (9:113536325 G>A)

Disease associations

OMIM: gene MIM:602189 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST008163_233	Height	5.000000e-07
GCST010002_278	Refractive error	4.000000e-08
GCST010083_163	Hemoglobin levels	4.000000e-11
GCST010083_174	Hemoglobin levels	5.000000e-12
GCST90002383_522	Hematocrit	5.000000e-19
GCST90002384_266	Hemoglobin	9.000000e-20
GCST90002403_617	Red blood cell count	4.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — R4 family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression	3
Acetaminophen	decreases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Cisplatin	increases expression	2
Progesterone	decreases expression, affects cotreatment	2
Silicon Dioxide	increases expression, decreases expression	2
Smoke	decreases expression, increases abundance	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
afimoxifene	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Valsartan	decreases reaction, increases expression	1
Benzo(a)pyrene	affects expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cobalt	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Demecolcine	increases expression	1
Diazinon	increases methylation	1

Clinical trials (associated diseases)

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