GPR20

Summary

GPR20 (G protein-coupled receptor 20, HGNC:4475) is a protein-coding gene on chromosome 8q24.3, encoding G-protein coupled receptor 20 (Q99678). Orphan receptor with constitutive G(i) signaling activity that activate cyclic AMP.

Enables G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of receptor complex.

Source: NCBI Gene 2843 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 101 total
• Druggable target: yes
• MANE Select transcript: NM_005293

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4475
Approved symbol	GPR20
Name	G protein-coupled receptor 20
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204882
Ensembl biotype	protein_coding
OMIM	601908
Entrez	2843

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000377741, ENST00000887272, ENST00000887273

RefSeq mRNA: 1 — MANE Select: NM_005293 NM_005293

CCDS: CCDS34949

Canonical transcript exons

ENST00000377741 — 2 exons

Exon	Start	End
ENSE00001474989	141356470	141357947
ENSE00001520912	141367201	141367286

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 95.75.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4438 / max 18.8871, expressed in 205 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95388	0.4438	205

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.58	gold quality
right coronary artery	UBERON:0001625	74.82	gold quality
popliteal artery	UBERON:0002250	72.65	gold quality
tibial artery	UBERON:0007610	72.61	gold quality
left coronary artery	UBERON:0001626	70.35	gold quality
mucosa of stomach	UBERON:0001199	68.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.39	gold quality
lower esophagus	UBERON:0013473	66.29	gold quality
smooth muscle tissue	UBERON:0001135	66.01	gold quality
descending thoracic aorta	UBERON:0002345	66.01	gold quality
left uterine tube	UBERON:0001303	65.47	gold quality
body of uterus	UBERON:0009853	65.41	gold quality
right lung	UBERON:0002167	64.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	64.25	gold quality
apex of heart	UBERON:0002098	63.86	gold quality
endocervix	UBERON:0000458	63.60	gold quality
fundus of stomach	UBERON:0001160	63.56	gold quality
thoracic aorta	UBERON:0001515	63.49	gold quality
ascending aorta	UBERON:0001496	63.09	gold quality
heart left ventricle	UBERON:0002084	62.84	gold quality
small intestine	UBERON:0002108	62.28	gold quality
body of stomach	UBERON:0001161	62.24	gold quality
myometrium	UBERON:0001296	62.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	62.07	gold quality
granulocyte	CL:0000094	61.93	gold quality
placenta	UBERON:0001987	61.92	gold quality
stomach	UBERON:0000945	61.54	gold quality
heart	UBERON:0000948	61.42	gold quality
upper lobe of left lung	UBERON:0008952	60.40	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting GPR20, 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-516B-5P	99.56	66.33	1495
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-3622B-5P	94.62	64.58	835
HSA-MIR-4746-3P	82.55	60.61	60

Literature-anchored findings (GeneRIF, showing 1)

• GPR20 constitutively activates G(i) proteins without ligand stimulation (PMID:18347022)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr20	ENSDARG00000077427
mus_musculus	Gpr20	ENSMUSG00000045281
rattus_norvegicus	Gpr20	ENSRNOG00000007795

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162)

Protein

Protein identifiers

G-protein coupled receptor 20 — Q99678 (reviewed: Q99678)

All UniProt accessions (1): Q99678

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor with constitutive G(i) signaling activity that activate cyclic AMP.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous with highest levels in intestinal tissues. In the brain detected in thalamus, putamen, and caudate, but not in frontal cortex, pons and hypothalamus.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_005284* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (43 total): helix 14, topological domain 8, transmembrane region 7, sequence variant 3, glycosylation site 2, sequence conflict 2, strand 2, chain 1, region of interest 1, compositionally biased region 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8HS2	ELECTRON MICROSCOPY	3.08
8HS3	ELECTRON MICROSCOPY	3.14
8HSC	ELECTRON MICROSCOPY	3.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99678-F1	79.89	0.48

Antibody-complex structures (SAbDab): 3 — 8HS2, 8HS3, 8HSC

Functional residue map

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

Glycosylation sites (2): 16, 26

Mutagenesis-validated functional residues (1):

Position	Phenotype
148	abolishes g(i) activation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 62 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GGGTGGRR_PAX4_03, SRF_Q5_01, SRF_01, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, SRF_C, ARGGGTTAA_UNKNOWN, GFI1_01, GOCC_RECEPTOR_COMPLEX, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, MIKKELSEN_IPS_LCP_WITH_H3K4ME3, MIKKELSEN_ES_LCP_WITH_H3K4ME3, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (2): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165)

GO Molecular Function (1): G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (3): plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

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
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR20	GPR22	Q99680	974
GPR20	GPR21	Q99679	938
GPR20	SST	P01166	495
GPR20	GPR26	Q8NDV2	490
GPR20	GPR61	Q9BZJ8	476
GPR20	GPR62	Q9BZJ7	464
GPR20	GPR52	Q9Y2T5	446
GPR20	ZNF528	Q3MIS6	424
GPR20	GPR150	Q8NGU9	418
GPR20	GPR3	P46089	388
GPR20	GPR101	Q96P66	382
GPR20	GPR27	Q9NS67	377
GPR20	GPR45	Q9Y5Y3	366
GPR20	CHRAC1	Q9NRG0	360
GPR20	OR4X1	Q8NH49	356

IntAct

13 interactions, top by confidence:

A	B	Type	Score
RAMP1	GPR20	psi-mi:“MI:0915”(physical association)	0.400
GPR20	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR20	psi-mi:“MI:0915”(physical association)	0.400
GPR20	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR20	psi-mi:“MI:0915”(physical association)	0.400
GPR20	RPL31	psi-mi:“MI:0915”(physical association)	0.370
POLR1H	GPR20	psi-mi:“MI:0915”(physical association)	0.370
JAM2	GPR20	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): JAM2 (Two-hybrid), ZNRD1 (Two-hybrid), RPL31 (Two-hybrid)

ESM2 similar proteins: A0A6I8PUB9, O00155, O00270, O14842, O14843, O15529, O43603, O46685, O60755, O88626, O88634, O88853, O88854, O88855, P0C5I1, P46092, P46093, P50132, Q149R9, Q15722, Q15743, Q1JQB3, Q3T181, Q3UFD7, Q3ZC80, Q4KLH9, Q6XKD3, Q76JU8, Q76JU9, Q76JV1, Q86VZ1, Q8BUD0, Q8BYC4, Q8HYC3, Q8K3T4, Q8TDS5, Q8TDU9, Q920E0, Q924U0, Q96G91

Diamond homologs: A0A6I8PUB9, A7YY44, B2GV46, F1MV99, O14842, O14843, O15529, O15552, P25116, P55085, P56488, Q00991, Q149R9, Q2HJA4, Q3T181, Q3UFD7, Q3ZC80, Q63645, Q63931, Q76EI6, Q76JU8, Q76JU9, Q76JV1, Q8K3T4, Q8VCK6, Q99678, Q9H1C0, E9QJ73, O09047, O42179, O43193, O55197, O88634, O88680, P30938, P46092, P46093, P47749, P50132, P58826

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

350 predictions. Top by Δscore:

Variant	Effect	Δscore
8:141367200:CCGCG:C	donor_gain	1.0000
8:141367197:TTA:T	donor_loss	0.9900
8:141367199:A:AC	donor_gain	0.9900
8:141367199:AC:A	donor_gain	0.9900
8:141367200:C:CC	donor_gain	0.9900
8:141367200:CC:C	donor_gain	0.9900
8:141367200:CCG:C	donor_gain	0.9900
8:141357943:CAGGC:C	acceptor_gain	0.9800
8:141357948:C:CC	acceptor_gain	0.9800
8:141367199:ACCG:A	donor_gain	0.9800
8:141367200:CCGC:C	donor_gain	0.9800
8:141357945:GGCCT:G	acceptor_loss	0.9600
8:141357947:CCTG:C	acceptor_loss	0.9600
8:141357948:CTGGA:C	acceptor_loss	0.9600
8:141357949:T:A	acceptor_loss	0.9600
8:141366089:A:C	donor_gain	0.9500
8:141357956:A:T	acceptor_loss	0.9400
8:141357946:GC:G	acceptor_gain	0.9300
8:141357947:CC:C	acceptor_gain	0.9300
8:141367207:TC:T	donor_gain	0.9300
8:141358097:C:CA	donor_gain	0.9200
8:141357945:GGC:G	acceptor_gain	0.9000
8:141357944:AGGC:A	acceptor_gain	0.8500
8:141366106:C:CT	donor_gain	0.8500
8:141358105:TC:T	donor_gain	0.8400
8:141358394:TA:T	donor_gain	0.8300
8:141358395:AA:A	donor_gain	0.8300
8:141357950:G:C	acceptor_loss	0.8100
8:141358086:AAATG:A	donor_gain	0.8100
8:141358106:C:CT	donor_gain	0.7900

AlphaMissense

2284 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:141357162:G:C	F254L	0.998
8:141357162:G:T	F254L	0.998
8:141357164:A:G	F254L	0.998
8:141357066:G:C	S286R	0.996
8:141357066:G:T	S286R	0.996
8:141357068:T:G	S286R	0.996
8:141357309:G:C	F205L	0.996
8:141357309:G:T	F205L	0.996
8:141357311:A:G	F205L	0.996
8:141357063:G:C	S287R	0.995
8:141357063:G:T	S287R	0.995
8:141357065:T:G	S287R	0.995
8:141357057:G:C	N289K	0.992
8:141357057:G:T	N289K	0.992
8:141357642:G:C	N94K	0.992
8:141357642:G:T	N94K	0.992
8:141357054:G:C	S290R	0.991
8:141357054:G:T	S290R	0.991
8:141357056:T:G	S290R	0.991
8:141357045:G:C	D293E	0.990
8:141357045:G:T	D293E	0.990
8:141357401:A:G	W175R	0.990
8:141357401:A:T	W175R	0.990
8:141357514:G:A	S137F	0.990
8:141357167:A:G	C253R	0.989
8:141357525:G:C	N133K	0.989
8:141357525:G:T	N133K	0.989
8:141357157:G:T	P256H	0.988
8:141357047:C:G	D293H	0.987
8:141357157:G:C	P256R	0.987

dbSNP variants (sampled 300 via entrez): RS1000272094 (8:141363580 T>G), RS1000472621 (8:141364050 G>A), RS1000591995 (8:141362990 T>C), RS1000880390 (8:141368479 C>G,T), RS1001492976 (8:141360989 C>T), RS1001674111 (8:141356647 G>A), RS1002320594 (8:141363372 A>G,T), RS1002425385 (8:141359034 C>A,T), RS1002476383 (8:141359292 C>A,T), RS1002529509 (8:141366740 C>T), RS1002640133 (8:141361712 G>A,C,T), RS1003035155 (8:141366539 C>T), RS1003093214 (8:141361902 C>T), RS1003165440 (8:141362138 C>T), RS1003402010 (8:141362902 C>T)

Disease associations

OMIM: gene MIM:601908 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001241_7	Bipolar disorder	9.000000e-06
GCST003437_5	Discordance in emotional problems in monozygotic twins	9.000000e-06
GCST003487_11	Response to fenofibrate (total cholesterol levels)	1.000000e-06
GCST004385_4	Systolic blood pressure	3.000000e-06
GCST004386_9	Diastolic blood pressure	4.000000e-11
GCST004388_19	Blood pressure traits (multi-trait analysis)	1.000000e-07
GCST004388_20	Blood pressure traits (multi-trait analysis)	2.000000e-08
GCST006020_39	Diastolic blood pressure	5.000000e-07
GCST006021_10	Systolic blood pressure	1.000000e-09
GCST007094_114	Diastolic blood pressure	1.000000e-07
GCST007099_8	Systolic blood pressure	4.000000e-08
GCST008044_13	Systolic blood pressure	5.000000e-07
GCST008044_2	Systolic blood pressure	7.000000e-09
GCST008362_184	Birth weight	8.000000e-08
GCST008839_518	Height	9.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007803	emotional symptom measurement
EFO:0007806	total cholesterol change measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004344	birth weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523912 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Class A Orphans with no pharmacology

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
propionaldehyde	increases expression	1
trichostatin A	decreases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1
Amphotericin B	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	increases expression	1
Cyclophosphamide	increases expression	1
Estradiol	increases expression	1
Gentamicins	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883438	Binding	PRESTO-Tango GPCRome screening (GPR20)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_KZ55	PathHunter HEK 293 GPR20 beta-arrestin	Transformed cell line	Female

Clinical trials (associated diseases)

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