RGS5

Summary

RGS5 (regulator of G protein signaling 5, HGNC:10001) is a protein-coding gene on chromosome 1q23.3, encoding Regulator of G-protein signaling 5 (O15539). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.

This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini.

Source: NCBI Gene 8490 — RefSeq curated summary.

At a glance

• Gene–disease (curated): essential hypertension, genetic (No Known Disease Relationship, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 26 total
• Phenotypes (HPO): 4
• MANE Select transcript: NM_003617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10001
Approved symbol	RGS5
Name	regulator of G protein signaling 5
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000143248
Ensembl biotype	protein_coding
OMIM	603276
Entrez	8490

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000313961, ENST00000367903, ENST00000428971, ENST00000469495, ENST00000525894, ENST00000527988, ENST00000530241, ENST00000530507, ENST00000531476, ENST00000531954, ENST00000534288, ENST00000618415, ENST00000950224

RefSeq mRNA: 12 — MANE Select: NM_003617 NM_001195303, NM_001254748, NM_001254749, NM_001414472, NM_001414473, NM_001414474, NM_001414475, NM_001414476, NM_001414477, NM_001414478, NM_001414479, NM_003617

CCDS: CCDS1244, CCDS55652, CCDS58041

Canonical transcript exons

ENST00000313961 — 5 exons

Exon	Start	End
ENSE00001158772	163202792	163202916
ENSE00003468643	163152550	163152716
ENSE00003513173	163168258	163168368
ENSE00003566635	163161915	163161976
ENSE00003749411	163142299	163147503

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.8339 / max 1536.2871, expressed in 1644 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15704	21.7169	642
15705	5.3053	1557
15691	0.4351	138
15689	0.1457	40
15692	0.1137	33
15693	0.0727	33
15690	0.0445	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.97	gold quality
descending thoracic aorta	UBERON:0002345	99.78	gold quality
cardia of stomach	UBERON:0001162	99.70	gold quality
urethra	UBERON:0000057	99.68	gold quality
pylorus	UBERON:0001166	99.61	gold quality
aorta	UBERON:0000947	99.60	gold quality
thoracic aorta	UBERON:0001515	99.60	gold quality
popliteal artery	UBERON:0002250	99.60	gold quality
tibial artery	UBERON:0007610	99.59	gold quality
ascending aorta	UBERON:0001496	99.58	gold quality
artery	UBERON:0001637	99.48	gold quality
visceral pleura	UBERON:0002401	99.48	gold quality
seminal vesicle	UBERON:0000998	99.45	gold quality
heart right ventricle	UBERON:0002080	99.44	gold quality
right coronary artery	UBERON:0001625	99.40	gold quality
mucosa of urinary bladder	UBERON:0001259	99.34	gold quality
vena cava	UBERON:0004087	99.29	gold quality
left ventricle myocardium	UBERON:0006566	99.16	gold quality
lower lobe of lung	UBERON:0008949	99.05	gold quality
colonic epithelium	UBERON:0000397	98.99	gold quality
myocardium	UBERON:0002349	98.99	gold quality
renal medulla	UBERON:0000362	98.94	gold quality
superficial temporal artery	UBERON:0001614	98.91	gold quality
gall bladder	UBERON:0002110	98.91	gold quality
parietal pleura	UBERON:0002400	98.90	gold quality
pons	UBERON:0000988	98.89	gold quality
pleura	UBERON:0000977	98.88	gold quality
biceps brachii	UBERON:0001507	98.83	gold quality
skin of hip	UBERON:0001554	98.81	gold quality
subthalamic nucleus	UBERON:0001906	98.74	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	7580.95
E-HCAD-31	yes	7258.73
E-HCAD-23	yes	6143.17
E-GEOD-124263	yes	5879.88
E-MTAB-6701	yes	5558.15
E-CURD-126	yes	5423.95
E-HCAD-11	yes	5148.03
E-GEOD-134144	yes	4889.17
E-CURD-46	yes	4421.01
E-MTAB-8381	yes	4153.63
E-MTAB-10287	yes	4018.76
E-ENAD-20	yes	3634.50
E-MTAB-9841	yes	3278.77
E-MTAB-8410	yes	3204.21
E-MTAB-6308	yes	2962.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, PPARD, PPARG

miRNA regulators (miRDB)

198 targeting RGS5, 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-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431

Literature-anchored findings (GeneRIF, showing 39)

• There is a contribution of RGS5 to schizophrenia susceptibility. (PMID:14755443)
• Elevated levels of RGS-5 in pericytes are also observed during wound healing and ovulation indicating a strong correlation between RGS-5 expression and active vessel remodeling. (PMID:15459006)
• The loss of RGS5 in the fibrous cap is of particular interest because of its role in vessel development and physiology and loss in fibrous cap of atherosclerosis (PMID:16293795)
• x-ray crystallography of the complex of RGS5 and Galphai(3) proteins with GDP/Mg(2+)/AlF(4)(-) at 3.0 A resolution (PMID:17100651)
• examined function, receptor specificity, and expression of R4 subfamily RGS proteins, RGS2, -3, -4, -5, and -8 via missense mutations introduced (PMID:17220356)
• RGS5 dimerization was confirmed by the analysis of a GFP tagged RGS5 fusion in yeast and with two-hybrid assays (PMID:17762159)
• Rgs5 and Notch3 are expressed in pericytes of developing and injured teeth and have roles along with vascular-derived stem cells during pulp healing (PMID:17939118)
• RGS5 genotypes predicted severity of baseline symptoms in schizophrenia. These data suggest a possible role for multiple RGS proteins in schizophrenia. (PMID:18262772)
• RGS5 is a novel HIF-1-dependent, hypoxia-induced gene that is involved in the induction of endothelial apoptosis. (PMID:19564336)
• Multiple SNPs in combination in RGS5 may confer risk for hypertension. Our results also lend support for the effect of RGS5 SNPs on lipid metabolism (PMID:19863299)
• used transgenic mice show that the cardiac constitutive expression of human Rgs5 protects against cardiac hypertrophy and fibrosis by blocking MEK-ERK1/2 signaling, whereas Rgs5-/- mice displayed the opposite phenotype. (PMID:20643937)
• RGS5 expression level in gastric carcinoma is associated with the differentiation and microvascular density of the tumor, and may be used as an important parameter for determining the prognosis of gastric carcinoma patients. (PMID:21105200)
• Repetitive beta(2)-agonist use may not only lead to reduced bronchoprotection but also to sensitization of excitation-contraction signaling pathways as a result of reduced RGS5 expression (PMID:21278382)
• regulator of G-protein signaling 5 can act as a physiological regulator of calcium sensing by calcium sensing receptor in the parathyroid gland (PMID:21393447)
• Low expression of RGS5 was strongly associated with cancer vasculature invasion and lymph node metastasis in non-small cell lung cancer. (PMID:21780128)
• examined polymorphisms in three genes (ATP1B1, RGS5 and SELE) in relation to hypertension and blood pressure in a cohort of African-Americans (PMID:21881522)
• demonstrate RGS5 in the blood vessels of other cancer models endowed with a proangiogenic environment, such as human melanoma and renal carcinoma xenografts (PMID:22130514)
• Our work identifies a new genetic variant in RGS5 demonstrating additive effect with PDE4D, both implicated in modulation of asthma treatment. (PMID:23193110)
• RGS1 is largely upregulated, whereas RGS2 is downregulated in the majority of solid tumors, whereas RGS5 transcripts are greatly increased in eight subtypes of lymphoma with no reports of downregulation in hematological malignancies (PMID:23464602)
• Over-expression of regulator of G protein signaling 5 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells. (PMID:23868206)
• 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)
• RGS5 enhanced the cytotoxic effect of radiation in the human lung cancer cells. Our results indicated that RGS5 may be a potential target for cancer therapy. (PMID:25891540)
• The pericyte marker RGS5 may be of future clinical utility for the evaluation of pericytic differentiation in soft tissue tumors. (PMID:26558691)
• Downregulation of RGS5 is an important prerequisite for smooth muscle cell proliferation in vascular injury model. (PMID:26663397)
• The chimeric RGS8 domains containing the first or the second exon part of RGS5 showed strong inhibitory effects similar to that of wild type RGS8, but the chimeric domain with the third exon part of RGS5 lost its activity (PMID:26754208)
• The rs16849802 of RGS5 and haplotype GAA independently increased the risk of essential hypertension in Mongolian patients, and may be used as a risk factor for the prediction of high blood pressure. (PMID:26782409)
• Rgs5 prevents vagal-related bradycardia and atrial tachycardia by negatively regulating the IKA Ach current. (PMID:26961238)
• Results show that RGS5 was highly expressed in the cytoplasm of epithelial ovarian cancer (EOC) cells and in microvascular structures. The expression of RGS5 in EOC was negatively associated with peritoneal metastasis. Hypoxia increased RGS5 expression in ovarian carcinomaderived endothelial cells (ODMECs). Further data indicated that RGS5 is crucial for the occurrence and development of ovarian cancer. (PMID:30365142)
• Expression and role of regulator of G-protein signaling 5 in squamous cell carcinoma of the tongue. (PMID:31049219)
• Down-regulated RGS5 by genetic variants impairs endothelial cell function and contributes to coronary artery disease. (PMID:31605122)
• Human cytomegalovirus promoting endothelial cell proliferation by targeting regulator of G-protein signaling 5 hypermethylation and downregulation. (PMID:32041970)
• RGS5 rs4657251 polymorphism is associated with small vessel occlusion stroke in Taiwan Han Chinese. (PMID:32080025)
• Hepatic Regulator of G Protein Signaling 5 Ameliorates Nonalcoholic Fatty Liver Disease by Suppressing Transforming Growth Factor Beta-Activated Kinase 1-c-Jun-N-Terminal Kinase/p38 Signaling. (PMID:32191345)
• In biopsy specimens of hepatocellular carcinoma, RGS5 and GPC3 expression were useful molecular makers for predicting portal vein invasion. (PMID:32620659)
• Integration of NRP1, RGS5, and FOXM1 expression, and tumour necrosis, as a postoperative prognostic classifier based on molecular subtypes of clear cell renal cell carcinoma. (PMID:34212534)
• RGS5 Attenuates Baseline Activity of ERK1/2 and Promotes Growth Arrest of Vascular Smooth Muscle Cells. (PMID:34359918)
• Implications of regulator of G-protein signaling 5 expression in the pathogenesis of primary and secondary hyperparathyroidism. (PMID:35681135)
• RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes. (PMID:36111549)
• Lnc-RGS5 sponges miR-542-5p to promote FoxM1/VEGFA signaling and breast cancer cell proliferation. (PMID:37594134)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs5a	ENSDARG00000002644
mus_musculus	Rgs5	ENSMUSG00000026678
rattus_norvegicus	Rgs5	ENSRNOG00000083506

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), 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 5 — O15539 (reviewed: O15539)

All UniProt accessions (3): O15539, B1APM2, E9PS96

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G(i)-alpha and G(o)-alpha, but not to G(s)-alpha.

Subcellular location. Cytoplasm. Membrane Cytoplasm.

Miscellaneous. Acts as an endogenous negative regulator of isoform 1.

Isoforms (3)

UniProt ID	Names	Canonical?
O15539-1	1	yes
O15539-2	2, RGS5s
O15539-3	3

RefSeq proteins (12): NP_001182232, NP_001241677, NP_001241678, NP_001401401, NP_001401402, NP_001401403, NP_001401404, NP_001401405, NP_001401406, NP_001401407, NP_001401408, NP_003608* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016137	RGS	Domain
IPR024066	RGS_subdom1/3	Homologous_superfamily
IPR034956	RGS_RGS5	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00615

UniProt features (15 total): helix 11, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CRP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15539-F1	86.31	0.72

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: 291 (showing top): MODULE_52, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, MODULE_64, GOBP_MUSCLE_CELL_PROLIFERATION, MODULE_313, PATIL_LIVER_CANCER, MODULE_66, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, CADWELL_ATG16L1_TARGETS_DN, ONKEN_UVEAL_MELANOMA_UP, MODULE_289, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, SASSON_RESPONSE_TO_FORSKOLIN_DN, CCTGTGA_MIR513

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), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706)

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

GO Cellular Component (4): 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
negative regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS5	GNB5	O14775	872
RGS5	SUCLG2	Q96I99	846
RGS5	GNAQ	P50148	786
RGS5	ARHGEF11	O15085	779
RGS5	ARHGEF1	Q92888	775
RGS5	RGSL1	A5PLK6	764
RGS5	GRK2	P25098	757
RGS5	MCF2	P10911	700
RGS5	GNA13	Q14344	692
RGS5	RGS7BP	Q6MZT1	679
RGS5	PLEK	P08567	670
RGS5	ARHGEF25	Q86VW2	666
RGS5	SUCLG1	P53597	664
RGS5	AKAP10	O43572	647
RGS5	PLEK2	Q9NYT0	643

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RGS5	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
ADO	RGS5	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
PCNA	RGS5	psi-mi:“MI:0915”(physical association)	0.370
RGS5	CST8	psi-mi:“MI:0914”(association)	0.350
RGS5	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): RGS5 (Two-hybrid), GNAI3 (Reconstituted Complex), GNAI2 (Reconstituted Complex), GNAO1 (Reconstituted Complex), OMP (Affinity Capture-MS), GNAI1 (Affinity Capture-Western), GNAI2 (Affinity Capture-Western), GNAI3 (Affinity Capture-Western), GNAO1 (Affinity Capture-Western), GNAQ (Affinity Capture-Western), RPP25L (Affinity Capture-MS), CST8 (Affinity Capture-MS), RGS5 (Cross-Linking-MS (XL-MS)), RPL37A (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A1A643, O08849, O08850, O14921, O15539, O35119, O43665, O46470, O54829, P34295, P41220, P49758, P49800, P49802, P49803, P49806, P49808, P49809, P79100, P97844, Q08116, Q09777, Q0P5H5, Q10955, Q2KHW7, Q2M5E4, Q3S853, Q3T0T8, Q4L0E8, Q5M8L6, Q62240, Q6DGI0, Q6RG78, Q864Z2, Q8K443, Q8VYB9, Q99PG4, Q9CQE5, Q9FLY5, Q9JHX0

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

920 predictions. Top by Δscore:

Variant	Effect	Δscore
1:163152549:CCT:C	donor_gain	1.0000
1:163152556:AGGAG:A	donor_gain	1.0000
1:163152563:T:TA	donor_gain	1.0000
1:163152596:G:A	donor_gain	1.0000
1:163152712:TCCAT:T	acceptor_gain	1.0000
1:163152713:CCAT:C	acceptor_gain	1.0000
1:163152713:CCATC:C	acceptor_gain	1.0000
1:163152714:CAT:C	acceptor_gain	1.0000
1:163152714:CATC:C	acceptor_gain	1.0000
1:163152715:AT:A	acceptor_gain	1.0000
1:163152717:C:CC	acceptor_gain	1.0000
1:163152717:CTG:C	acceptor_loss	1.0000
1:163152718:T:C	acceptor_loss	1.0000
1:163161908:AACTT:A	donor_loss	1.0000
1:163161909:ACTTA:A	donor_loss	1.0000
1:163161910:CTTAC:C	donor_loss	1.0000
1:163161911:TTAC:T	donor_loss	1.0000
1:163161912:T:TG	donor_loss	1.0000
1:163161913:A:AC	donor_gain	1.0000
1:163161914:C:CC	donor_gain	1.0000
1:163161914:C:CT	donor_loss	1.0000
1:163161914:CA:C	donor_gain	1.0000
1:163161914:CAG:C	donor_gain	1.0000
1:163161984:A:T	acceptor_gain	1.0000
1:163161988:A:AC	acceptor_gain	1.0000
1:163168251:GACTC:G	donor_loss	1.0000
1:163168252:ACT:A	donor_loss	1.0000
1:163168253:CTC:C	donor_loss	1.0000
1:163168254:TCACT:T	donor_loss	1.0000
1:163168255:CACTT:C	donor_loss	1.0000

AlphaMissense

1208 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:163152574:G:C	F120L	0.999
1:163152574:G:T	F120L	0.999
1:163152576:A:G	F120L	0.999
1:163152656:A:G	F93S	0.999
1:163152691:G:C	F81L	0.999
1:163152691:G:T	F81L	0.999
1:163152693:A:G	F81L	0.999
1:163147383:G:T	R169S	0.998
1:163152655:G:C	F93L	0.998
1:163152655:G:T	F93L	0.998
1:163152657:A:G	F93L	0.998
1:163152676:G:C	F86L	0.998
1:163152676:G:T	F86L	0.998
1:163152678:A:G	F86L	0.998
1:163152689:A:G	L82P	0.998
1:163147378:A:C	F170L	0.997
1:163147378:A:T	F170L	0.997
1:163147379:A:G	F170S	0.997
1:163147380:A:G	F170L	0.997
1:163147406:A:G	L161P	0.997
1:163147427:G:T	A154D	0.997
1:163147498:A:C	N130K	0.997
1:163147498:A:T	N130K	0.997
1:163147382:C:G	R169P	0.996
1:163152597:C:G	A113P	0.996
1:163152643:A:C	C97W	0.996
1:163152668:T:A	E89V	0.996
1:163152673:A:C	S87R	0.996
1:163152673:A:T	S87R	0.996
1:163152675:T:G	S87R	0.996

dbSNP variants (sampled 300 via entrez): RS1000008497 (1:163256173 C>T), RS1000018021 (1:163170025 A>T), RS1000032625 (1:163184705 G>A), RS1000037315 (1:163273666 G>C), RS1000048839 (1:163307385 T>G), RS1000124298 (1:163263100 A>G), RS1000153136 (1:163256881 A>T), RS1000161457 (1:163282194 C>T), RS1000163318 (1:163270503 G>C), RS1000169271 (1:163219982 T>C), RS1000173011 (1:163322079 G>A), RS1000189584 (1:163148561 C>T), RS1000252574 (1:163236714 A>C), RS1000252697 (1:163229725 C>A), RS1000265315 (1:163226223 G>A)

Disease associations

OMIM: gene MIM:603276 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
essential hypertension, genetic	No Known Disease Relationship	Unknown

Mondo (1): essential hypertension, genetic (MONDO:0007781)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0001426	Non-Mendelian inheritance
HP:0004421	Elevated systolic blood pressure
HP:0004972	Elevated mean arterial pressure
HP:0005117	Elevated diastolic blood pressure

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002156_1	Response to mTOR inhibitor (rapamycin)	4.000000e-06
GCST002207_6	Liver enzyme levels (alanine transaminase)	4.000000e-06
GCST002759_28	Motion sickness	3.000000e-09
GCST002831_3	Lead levels in blood	3.000000e-06
GCST008163_553	Height	4.000000e-08
GCST012007_4	Hypoalbuminemia	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005417	response to mTOR inhibitor
EFO:0006928	motion sickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1056515	Efficacy	3	bevacizumab;fluorouracil;irinotecan;leucovorin	Colorectal Neoplasms

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1056515	RGS5	3	2.00	1	bevacizumab;fluorouracil;irinotecan;leucovorin
rs2661280	RGS5		0.00	0
rs11580141	RGS5		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — R4 family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	6
methylmercuric chloride	decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	3
Silicon Dioxide	decreases expression	3
Tretinoin	decreases expression, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Estradiol	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Okadaic Acid	affects expression, decreases expression	2
Esketamine	decreases expression	1
bufotalin	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	decreases expression	1
bisphenol A	affects methylation	1
deoxynivalenol	decreases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression	1
pentanal	decreases expression	1
avobenzone	decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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