RGS11

Summary

RGS11 (regulator of G protein signaling 11, HGNC:9993) is a protein-coding gene on chromosome 16p13.3, encoding Regulator of G-protein signaling 11 (O94810). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.

The protein encoded by this gene belongs to the RGS (regulator of G protein signaling) family. Members of the RGS family act as GTPase-activating proteins on the alpha subunits of heterotrimeric, signal-transducing G proteins. This protein inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Alternative splicing occurs at this locus and four transcript variants encoding distinct isoforms have been identified.

Source: NCBI Gene 8786 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 110 total
• MANE Select transcript: NM_183337

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9993
Approved symbol	RGS11
Name	regulator of G protein signaling 11
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000076344
Ensembl biotype	protein_coding
OMIM	603895
Entrez	8786

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000168869, ENST00000316163, ENST00000359740, ENST00000397770, ENST00000472466, ENST00000477143, ENST00000481672, ENST00000493449, ENST00000896542, ENST00000960873

RefSeq mRNA: 4 — MANE Select: NM_183337 NM_001286485, NM_001286486, NM_003834, NM_183337

CCDS: CCDS10403, CCDS42088, CCDS66884

Canonical transcript exons

ENST00000397770 — 17 exons

Exon	Start	End
ENSE00001779596	274976	275082
ENSE00001957809	275849	275944
ENSE00003466861	271399	271460
ENSE00003481099	272863	272931
ENSE00003503182	270984	271099
ENSE00003503577	270523	270661
ENSE00003526209	271540	271569
ENSE00003544070	271202	271315
ENSE00003544281	273760	273836
ENSE00003560838	269503	269585
ENSE00003563262	274043	274101
ENSE00003569947	273475	273556
ENSE00003600518	270744	270831
ENSE00003646330	274214	274265
ENSE00003658739	275283	275333
ENSE00003684171	268307	269383
ENSE00003755665	275402	275498

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 99.23.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2590 / max 97.1473, expressed in 394 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155714	1.2590	394

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.23	gold quality
cerebellar hemisphere	UBERON:0002245	98.87	gold quality
cerebellar cortex	UBERON:0002129	98.65	gold quality
right frontal lobe	UBERON:0002810	96.93	gold quality
cerebellum	UBERON:0002037	96.90	gold quality
adenohypophysis	UBERON:0002196	96.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.08	gold quality
pituitary gland	UBERON:0000007	94.66	gold quality
cingulate cortex	UBERON:0003027	92.87	gold quality
anterior cingulate cortex	UBERON:0009835	92.75	gold quality
spinal cord	UBERON:0002240	92.63	gold quality
tibial nerve	UBERON:0001323	92.58	gold quality
amygdala	UBERON:0001876	92.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.84	gold quality
apex of heart	UBERON:0002098	91.31	gold quality
nucleus accumbens	UBERON:0001882	90.93	gold quality
right atrium auricular region	UBERON:0006631	90.12	gold quality
caudate nucleus	UBERON:0001873	90.00	gold quality
right coronary artery	UBERON:0001625	89.89	gold quality
mucosa of transverse colon	UBERON:0004991	89.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.11	gold quality
putamen	UBERON:0001874	88.88	gold quality
hypothalamus	UBERON:0001898	88.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.36	gold quality
cardiac atrium	UBERON:0002081	88.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.01	gold quality
lower esophagus	UBERON:0013473	87.97	gold quality
left coronary artery	UBERON:0001626	87.63	gold quality
central nervous system	UBERON:0001017	87.35	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	1988.16
E-ANND-3	yes	3.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting RGS11, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-558	97.50	67.16	977
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-4740-5P	96.25	67.96	726
HSA-MIR-6749-5P	89.28	58.87	75

Literature-anchored findings (GeneRIF, showing 3)

• the successful purification of functionally intact Gbeta5-free recombinant RGS11 was reported that differentially interact with R7BP and Galpha(oa). (PMID:19497306)
• In granulosa cells, there are significant changes in expression during follicular maturation. (PMID:24828608)
• Overexpression of RGS11 promotes cell migration, participates in tumor metastasis, and correlates the clinicopathological conditions of patients with lung adenocarcinoma. (PMID:27105500)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs11	ENSDARG00000037646
mus_musculus	Rgs11	ENSMUSG00000024186

Paralogs (23): 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), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 11 — O94810 (reviewed: O94810)

All UniProt accessions (3): O94810, H7C5Z0, Q4TT70

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.

Subunit / interactions. Heterodimer with Gbeta5. Interacts with RGS7BP, leading to regulate the subcellular location of the heterodimer formed with Gbeta5.

Isoforms (3)

UniProt ID	Names	Canonical?
O94810-1	1	yes
O94810-2	2
O94810-3	3

RefSeq proteins (4): NP_001273414, NP_001273415, NP_003825, NP_899180* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000591	DEP_dom	Domain
IPR015898	G-protein_gamma-like_dom	Domain
IPR016137	RGS	Domain
IPR036284	GGL_sf	Homologous_superfamily
IPR036305	RGS_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040759	RGS_DHEX	Domain
IPR044926	RGS_subdomain_2	Homologous_superfamily
IPR047016	RGS6/7/9/11	Family
IPR047017	RGS6/7/9/11_DHEX_sf	Homologous_superfamily

Pfam: PF00610, PF00615, PF00631, PF18148

UniProt features (11 total): domain 3, mutagenesis site 2, splice variant 2, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94810-F1	87.02	0.75

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
274	diminishes interaction with gbeta5.
245	diminishes interaction with gbeta5.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding

MSigDB gene sets: 87 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, WANG_RESPONSE_TO_BEXAROTENE_UP, GOCC_NEURON_PROJECTION, GAVIN_FOXP3_TARGETS_CLUSTER_P2, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOBP_REGULATION_OF_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

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), intracellular signal transduction (GO:0035556)

GO Molecular Function (3): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), G-protein beta-subunit binding (GO:0031681)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Chaperonin-mediated protein folding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	3
regulation of signal transduction	2
intracellular anatomical structure	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
protein binding	1
cellular anatomical structure	1
membrane	1
cell periphery	1
cellular_component	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS11	GNB5	O14775	998
RGS11	RGS7BP	Q6MZT1	964
RGS11	RGS9BP	Q6ZS82	931
RGS11	SUCLG2	Q96I99	899
RGS11	GGT5	P36269	859
RGS11	ARHGEF1	Q92888	793
RGS11	GNAQ	P50148	778
RGS11	ARHGEF11	O15085	777
RGS11	GRK2	P25098	776
RGS11	RGSL1	A5PLK6	756
RGS11	PLEK	P08567	739
RGS11	GNA13	Q14344	715
RGS11	SUCLG1	P53597	709
RGS11	PLEK2	Q9NYT0	705
RGS11	MCF2	P10911	695

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RGS11	H1-2	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	RGS11	psi-mi:“MI:0915”(physical association)	0.400
CDC37	RGS11	psi-mi:“MI:0915”(physical association)	0.400
SNTA1	GNAT3	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): RGS11 (Affinity Capture-MS), RGS11 (Affinity Capture-MS), HIST1H1C (Proximity Label-MS), RGS11 (Affinity Capture-MS), RGS11 (Affinity Capture-MS), CCDC127 (Cross-Linking-MS (XL-MS)), AP1AR (Cross-Linking-MS (XL-MS)), RGS11 (Affinity Capture-MS), GNB5 (Affinity Capture-Western), GNB5 (Affinity Capture-Western), GNB5 (Reconstituted Complex), GNB5 (Co-purification), RGS11 (Affinity Capture-Luminescence), RGS11 (Affinity Capture-MS), RGS11 (PCA)

ESM2 similar proteins: A2VDW6, A4D2P6, A8VU90, B0BNK9, E9PY61, F1LQY6, O94810, O95382, Q05AA6, Q0QWG9, Q13474, Q2TBQ9, Q3KR56, Q3UFQ8, Q3UR97, Q3V3V9, Q5FVC2, Q5R8E2, Q5XHY1, Q60875, Q61085, Q6F5E8, Q6P597, Q6P5Z2, Q6PRD1, Q6V7V2, Q80XL1, Q80ZJ8, Q865S3, Q86UD0, Q8C6B2, Q8K031, Q8K045, Q8N4Y2, Q8ND23, Q91W40, Q91ZP9, Q92502, Q92974, Q969H4

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2952 predictions. Top by Δscore:

Variant	Effect	Δscore
16:270518:CCCA:C	donor_loss	1.0000
16:270520:CACCT:C	donor_loss	1.0000
16:270521:A:T	donor_loss	1.0000
16:270522:C:CG	donor_loss	1.0000
16:270522:CCTT:C	donor_gain	1.0000
16:270657:ACTGC:A	acceptor_loss	1.0000
16:270658:CTGC:C	acceptor_gain	1.0000
16:270659:TGCCT:T	acceptor_loss	1.0000
16:270660:GCCT:G	acceptor_loss	1.0000
16:270661:CCTAG:C	acceptor_loss	1.0000
16:270662:C:CC	acceptor_gain	1.0000
16:270663:T:G	acceptor_loss	1.0000
16:270742:A:AC	donor_gain	1.0000
16:270743:C:CC	donor_gain	1.0000
16:270743:CT:C	donor_gain	1.0000
16:270983:CCA:C	donor_gain	1.0000
16:271095:CCACC:C	acceptor_gain	1.0000
16:271096:CACCC:C	acceptor_gain	1.0000
16:271098:CC:C	acceptor_gain	1.0000
16:271099:CC:C	acceptor_gain	1.0000
16:271200:A:AC	donor_gain	1.0000
16:271201:C:CC	donor_gain	1.0000
16:272927:CCGGG:C	acceptor_gain	1.0000
16:272928:CGGGC:C	acceptor_gain	1.0000
16:273555:CC:C	acceptor_gain	1.0000
16:273556:CC:C	acceptor_gain	1.0000
16:273756:TCAC:T	donor_loss	1.0000
16:273757:CAC:C	donor_loss	1.0000
16:273758:A:T	donor_loss	1.0000
16:273759:C:CA	donor_loss	1.0000

AlphaMissense

3043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:270655:G:C	F358L	0.992
16:270655:G:T	F358L	0.992
16:270657:A:G	F358L	0.992
16:269568:G:C	F408L	0.985
16:269568:G:T	F408L	0.985
16:269569:A:G	F408S	0.985
16:269570:A:G	F408L	0.985
16:271003:A:C	F320L	0.985
16:271003:A:T	F320L	0.985
16:271005:A:G	F320L	0.985
16:271245:A:G	W274R	0.981
16:271245:A:T	W274R	0.981
16:270815:G:C	F332L	0.980
16:270815:G:T	F332L	0.980
16:270817:A:G	F332L	0.980
16:270988:G:C	F325L	0.980
16:270988:G:T	F325L	0.980
16:270990:A:G	F325L	0.980
16:269579:A:C	Y405D	0.978
16:271065:A:G	W300R	0.977
16:271065:A:T	W300R	0.977
16:270542:A:T	I396K	0.976
16:270625:G:C	N368K	0.976
16:270625:G:T	N368K	0.976
16:271063:C:A	W300C	0.974
16:271063:C:G	W300C	0.974
16:269572:C:A	R407M	0.967
16:270816:A:G	F332S	0.967
16:271013:A:G	F317S	0.965
16:274979:G:C	F105L	0.965

dbSNP variants (sampled 300 via entrez): RS1000133880 (16:272853 A>G), RS1000299354 (16:268363 G>A), RS1000389084 (16:275558 C>T), RS1000734465 (16:273634 G>A), RS1000767682 (16:271747 G>A), RS1000800389 (16:274243 G>A,T), RS1000825441 (16:274701 G>A), RS1001705831 (16:275508 G>A), RS1001767884 (16:275020 G>A,C), RS1002035262 (16:267958 G>A), RS1002087808 (16:268155 T>A,C), RS1002383218 (16:268565 C>A,T), RS1003157214 (16:269812 CT>C), RS1003581004 (16:277833 A>G), RS1003650428 (16:269972 G>A,C)

Disease associations

OMIM: gene MIM:603895 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000587_1	Mean corpuscular hemoglobin	3.000000e-09
GCST005951_12	Body mass index	5.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004340	body mass index

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 — R7 family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bufotalin	decreases expression	1
perfluorooctanoic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
ICG 001	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Fluvastatin	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	decreases expression	1
Copper	affects binding, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Disulfiram	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Folic Acid	increases expression	1
Ivermectin	decreases expression	1
Silicon Dioxide	increases expression	1
Testosterone	affects cotreatment, increases expression, decreases expression	1
Tetradecanoylphorbol Acetate	affects expression, affects cotreatment	1
Triclosan	increases expression	1
Tunicamycin	increases expression	1
Valproic Acid	increases methylation	1
Zinc	affects cotreatment, affects expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Thapsigargin	increases expression	1

Clinical trials (associated diseases)

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