RGS21

Summary

RGS21 (regulator of G protein signaling 21, HGNC:26839) is a protein-coding gene on chromosome 1q31.2, encoding Regulator of G-protein signaling 21 (Q2M5E4). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.

Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins are GTPase-activating proteins for Gi (see GNAI1; MIM 139310) and Gq (see GNAQ; MIM 600998) class G-alpha proteins. They accelerate transit through the cycle of GTP binding and hydrolysis and thereby accelerate signaling kinetics and termination.

Source: NCBI Gene 431704 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_001039152

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26839
Approved symbol	RGS21
Name	regulator of G protein signaling 21
Location	1q31.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000253148
Ensembl biotype	protein_coding
OMIM	612407
Entrez	431704

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000417209

RefSeq mRNA: 1 — MANE Select: NM_001039152 NM_001039152

CCDS: CCDS41448

Canonical transcript exons

ENST00000417209 — 5 exons

Exon	Start	End
ENSE00002211405	192347313	192347389
ENSE00002265119	192365921	192367285
ENSE00002282514	192352047	192352213
ENSE00002290291	192316992	192317105
ENSE00002303776	192342977	192343047

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 45.47.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	45.47	gold quality
sural nerve	UBERON:0015488	38.94	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
granulocyte	CL:0000094	35.58	gold quality
skeletal muscle tissue	UBERON:0001134	35.20	gold quality
tonsil	UBERON:0002372	32.66	gold quality
muscle tissue	UBERON:0002385	32.40	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
leukocyte	CL:0000738	31.54	gold quality
monocyte	CL:0000576	31.36	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.69	gold quality
calcaneal tendon	UBERON:0003701	29.08	gold quality
liver	UBERON:0002107	28.30	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	26.91	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.35	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
frontal cortex	UBERON:0001870	24.75	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
pancreas	UBERON:0001264	24.36	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
kidney	UBERON:0002113	23.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting RGS21, 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-6740-5P	100.00	65.64	932
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-4328	99.57	71.06	4094

Literature-anchored findings (GeneRIF, showing 2)

• RGS21 mRNA is expressed ubiquitously in the 16 tissues examined, implying general physiological roles. (PMID:16302027)
• RGS21 modulates bitter taste signal transduction. (PMID:23095746)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-196h16.12	ENSDARG00000028276
mus_musculus	Rgs21	ENSMUSG00000098509
rattus_norvegicus	Rgs21	ENSRNOG00000056369

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), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901)

Protein

Protein identifiers

Regulator of G-protein signaling 21 — Q2M5E4 (reviewed: Q2M5E4)

All UniProt accessions (1): Q2M5E4

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.

Tissue specificity. Expressed ubiquitously.

RefSeq proteins (1): NP_001034241* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00615

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2M5E4-F1	85.05	0.74

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: 49 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_SENSORY_PERCEPTION_OF_TASTE, GOBP_SENSORY_PERCEPTION, GOCC_CYTOPLASMIC_SIDE_OF_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, 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, GOBP_NEGATIVE_REGULATION_OF_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_BITTER_TASTE

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), negative regulation of signal transduction (GO:0009968), transmission of nerve impulse (GO:0019226), sensory perception of bitter taste (GO:0050913), sensory perception of sweet taste (GO:0050916), sensory perception of umami taste (GO:0050917)

GO Molecular Function (1): GTPase activity (GO:0003924)

GO Cellular Component (1): plasma membrane (GO:0005886)

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
sensory perception of taste	3
signal transduction	2
G protein-coupled receptor activity	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
action potential	1
cell communication	1
chemical synaptic transmission	1
nervous system process	1
ribonucleoside triphosphate phosphatase activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

984 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS21	GNB5	O14775	882
RGS21	SUCLG2	Q96I99	861
RGS21	ARHGEF1	Q92888	799
RGS21	GNAQ	P50148	794
RGS21	ARHGEF11	O15085	793
RGS21	GRK2	P25098	771
RGS21	RGSL1	A5PLK6	771
RGS21	RGS7BP	Q6MZT1	723
RGS21	MCF2	P10911	722
RGS21	SUCLG1	P53597	721
RGS21	GNA13	Q14344	716
RGS21	PLEK	P08567	704
RGS21	AKAP10	O43572	673
RGS21	PLEK2	Q9NYT0	670
RGS21	ARHGEF25	Q86VW2	666

IntAct

0 interactions, top by confidence:

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

985 predictions. Top by Δscore:

Variant	Effect	Δscore
1:192317101:TTTGT:T	donor_gain	1.0000
1:192317104:GT:G	donor_gain	1.0000
1:192317106:G:GG	donor_gain	1.0000
1:192352045:A:AG	acceptor_gain	1.0000
1:192352045:AGCT:A	acceptor_gain	1.0000
1:192352046:G:GG	acceptor_gain	1.0000
1:192352046:GCTG:G	acceptor_gain	1.0000
1:192317078:A:T	donor_gain	0.9900
1:192317102:TTGT:T	donor_gain	0.9900
1:192317103:TGTGT:T	donor_loss	0.9900
1:192317105:TG:T	donor_loss	0.9900
1:192317106:GTGA:G	donor_loss	0.9900
1:192317108:G:GT	donor_loss	0.9900
1:192343043:GTGAA:G	donor_gain	0.9900
1:192343048:G:GG	donor_gain	0.9900
1:192352046:GCT:G	acceptor_gain	0.9900
1:192364503:C:G	acceptor_gain	0.9900
1:192365915:CCACA:C	acceptor_loss	0.9900
1:192365916:CACAG:C	acceptor_loss	0.9900
1:192365917:ACAG:A	acceptor_loss	0.9900
1:192365918:CAG:C	acceptor_loss	0.9900
1:192365919:A:AG	acceptor_gain	0.9900
1:192365919:AGA:A	acceptor_loss	0.9900
1:192365920:G:A	acceptor_loss	0.9900
1:192365920:G:GG	acceptor_gain	0.9900
1:192317077:G:GT	donor_gain	0.9800
1:192335242:C:CG	donor_gain	0.9800
1:192352043:ATAG:A	acceptor_loss	0.9800
1:192352044:TA:T	acceptor_loss	0.9800
1:192352045:A:C	acceptor_loss	0.9800

AlphaMissense

1018 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:192352187:T:C	F77L	0.998
1:192352189:C:A	F77L	0.998
1:192352189:C:G	F77L	0.998
1:192352070:T:C	F38L	0.997
1:192352072:T:A	F38L	0.997
1:192352072:T:G	F38L	0.997
1:192352106:T:C	F50L	0.996
1:192352108:C:A	F50L	0.996
1:192352108:C:G	F50L	0.996
1:192366045:T:C	F127S	0.996
1:192366044:T:C	F127L	0.995
1:192366046:T:A	F127L	0.995
1:192366046:T:G	F127L	0.995
1:192352107:T:C	F50S	0.994
1:192352085:T:C	F43L	0.992
1:192352087:T:A	F43L	0.992
1:192352087:T:G	F43L	0.992
1:192352120:T:G	C54W	0.991
1:192352166:G:C	A70P	0.991
1:192352074:T:C	L39P	0.990
1:192365922:T:G	I86S	0.990
1:192366018:T:C	L118P	0.990
1:192352115:G:C	A53P	0.989
1:192352119:G:A	C54Y	0.989
1:192366053:T:C	S130P	0.989
1:192352062:T:C	F35S	0.988
1:192352088:A:C	S44R	0.988
1:192352090:T:A	S44R	0.988
1:192352090:T:G	S44R	0.988
1:192365926:C:A	N87K	0.988

dbSNP variants (sampled 300 via entrez): RS1000143712 (1:192315121 G>A), RS1000211123 (1:192332439 T>C), RS1000215538 (1:192339676 T>C), RS1000411197 (1:192332210 A>T), RS1000437879 (1:192350684 G>A), RS1000494102 (1:192337916 T>A), RS1000519021 (1:192333543 A>G), RS1000537778 (1:192350867 G>A), RS1000585990 (1:192328127 C>T), RS1000651524 (1:192342835 T>C), RS1000665834 (1:192315065 GA>G), RS1000683401 (1:192326728 T>C), RS1000831920 (1:192322702 C>G), RS1000846509 (1:192320893 C>T), RS1000893565 (1:192350420 T>C)

Disease associations

OMIM: gene MIM:612407 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001598_1	Blood pressure	9.000000e-07
GCST003262_335	Post bronchodilator FEV1	3.000000e-06
GCST003489_1	Food addiction	2.000000e-07
GCST009391_538	Metabolite levels	5.000000e-06
GCST009597_294	Multiple sclerosis	4.000000e-33
GCST011096_20	Systemic lupus erythematosus	2.000000e-07
GCST012636_2	Systemic vasculitis	4.000000e-06
GCST90011866_8	Systemic lupus erythematosus	5.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0007829	eating behaviour
EFO:0007830	food addiction measurement
EFO:0010528	quinolinic acid measurement

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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation	1
Dinitrochlorobenzene	affects binding	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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