GPR22

Summary

GPR22 (G protein-coupled receptor 22, HGNC:4477) is a protein-coding gene on chromosome 7q22.3, encoding G-protein coupled receptor 22 (Q99680). Orphan G-protein coupled receptor.

This gene is a member of the G-protein coupled receptor 1 family and encodes a multi-pass membrane protein.

Source: NCBI Gene 2845 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 3 total
• Druggable target: yes
• MANE Select transcript: NM_005295

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4477
Approved symbol	GPR22
Name	G protein-coupled receptor 22
Location	7q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172209
Ensembl biotype	protein_coding
OMIM	601910
Entrez	2845

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000304402, ENST00000473300, ENST00000496754, ENST00000890166, ENST00000960458, ENST00000960459

RefSeq mRNA: 1 — MANE Select: NM_005295 NM_005295

CCDS: CCDS5744

Canonical transcript exons

ENST00000304402 — 3 exons

Exon	Start	End
ENSE00001174047	107474035	107475684
ENSE00001413461	107471372	107472302
ENSE00001414143	107470057	107470445

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 95.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8244 / max 172.2434, expressed in 130 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80443	1.5695	124
80444	0.1965	75
204643	0.0584	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.24	gold quality
superior frontal gyrus	UBERON:0002661	89.87	gold quality
prefrontal cortex	UBERON:0000451	86.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.60	gold quality
frontal cortex	UBERON:0001870	84.36	gold quality
cerebral cortex	UBERON:0000956	83.44	gold quality
anterior cingulate cortex	UBERON:0009835	82.91	gold quality
primary visual cortex	UBERON:0002436	81.70	gold quality
right frontal lobe	UBERON:0002810	81.05	gold quality
heart left ventricle	UBERON:0002084	80.23	gold quality
Ammon’s horn	UBERON:0001954	79.51	gold quality
cardiac atrium	UBERON:0002081	79.13	gold quality
right atrium auricular region	UBERON:0006631	79.13	gold quality
corpus callosum	UBERON:0002336	76.97	gold quality
cerebellar cortex	UBERON:0002129	76.65	gold quality
cerebellum	UBERON:0002037	76.52	gold quality
cerebellar hemisphere	UBERON:0002245	76.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.09	gold quality
heart	UBERON:0000948	75.88	gold quality
amygdala	UBERON:0001876	75.18	gold quality
temporal lobe	UBERON:0001871	75.17	gold quality
brain	UBERON:0000955	73.11	gold quality
adrenal tissue	UBERON:0018303	72.76	gold quality
apex of heart	UBERON:0002098	72.56	gold quality
caudate nucleus	UBERON:0001873	67.74	gold quality
bone marrow cell	CL:0002092	67.42	silver quality
calcaneal tendon	UBERON:0003701	66.99	gold quality
ventricular zone	UBERON:0003053	66.41	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6075	no	460.83
E-ANND-3	no	1.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting GPR22, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 2)

• Demonstrate GRR22 expression in human heart. (PMID:18539757)
• Cardiomyocyte-specific overexpression of GPR22 ameliorates cardiac injury in mice with acute myocardial infarction. (PMID:38816768)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr22a	ENSDARG00000004592
danio_rerio	gpr22b	ENSDARG00000045383
mus_musculus	Gpr22	ENSMUSG00000044067
rattus_norvegicus	Gpr22	ENSRNOG00000008423
drosophila_melanogaster	CrzR	FBGN0036278
caenorhabditis_elegans		WBGENE00013642

Paralogs (16): NPFFR2 (ENSG00000056291), GNRHR (ENSG00000109163), CCKBR (ENSG00000110148), HCRTR1 (ENSG00000121764), AVPR2 (ENSG00000126895), GALR3 (ENSG00000128310), HCRTR2 (ENSG00000137252), NPFFR1 (ENSG00000148734), CCKAR (ENSG00000163394), AVPR1A (ENSG00000166148), GALR1 (ENSG00000166573), GPR150 (ENSG00000178015), OXTR (ENSG00000180914), FFAR4 (ENSG00000186188), QRFPR (ENSG00000186867), AVPR1B (ENSG00000198049)

Protein

Protein identifiers

G-protein coupled receptor 22 — Q99680 (reviewed: Q99680)

All UniProt accessions (1): Q99680

UniProt curated annotations — full annotation on UniProt →

Function. Orphan G-protein coupled receptor. Seems to act through a G(i)/G(o) mediated pathway. May be involved in ciliogenesis.

Subcellular location. Cell membrane.

Tissue specificity. High expression in adult and fetal heart tissue. Expressed in the brain, with enrichment in the accumbens, amygdala, cerebellum, cortex, and hippocampus regions.

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

RefSeq proteins (1): NP_005286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (19 total): topological domain 8, transmembrane region 7, glycosylation site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99680-F1	72.19	0.32

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, 192

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): WWTAAGGC_UNKNOWN, LHX3_01, EFC_Q6, EVI1_05, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, WTGAAAT_UNKNOWN, TGACATY_UNKNOWN, GOBP_RESPONSE_TO_HORMONE, AACTTT_UNKNOWN, GOBP_CELL_PROJECTION_ORGANIZATION, MYB_Q5_01, TGGAAA_NFAT_Q4_01, TAATTA_CHX10_01, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

GO Biological Process (4): G protein-coupled receptor signaling pathway (GO:0007186), cell projection organization (GO:0030030), cellular response to hormone stimulus (GO:0032870), signal transduction (GO:0007165)

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

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	1
signal transduction	1
cellular component organization	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	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
cellular anatomical structure	1

Protein interactions and networks

STRING

754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR22	GPR20	Q99678	974
GPR22	LPAR4	Q99677	864
GPR22	CMKLR2	P46091	816
GPR22	DUS4L	O95620	733
GPR22	COG5	Q9UP83	699
GPR22	BCAP29	Q9UHQ4	644
GPR22	SST	P01166	520
GPR22	PRKAR2B	P31323	503
GPR22	GPR142	Q7Z601	503
GPR22	CCDC174	Q6PII3	487
GPR22	GPR63	Q9BZJ6	483
GPR22	GPR176	Q14439	483
GPR22	GPR19	Q15760	467
GPR22	GPR162	Q16538	456
GPR22	MCF2L	O15068	443

IntAct

5 interactions, top by confidence:

A	B	Type	Score
GPR22	CEBPE	psi-mi:“MI:0915”(physical association)	0.370
NFATC4	GPR22	psi-mi:“MI:0915”(physical association)	0.370
GPR22	TFAP2C	psi-mi:“MI:0915”(physical association)	0.370
ARGLU1	PIAS2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (3): NFATC4 (Two-hybrid), TFAP2C (Two-hybrid), GPR22 (Two-hybrid)

ESM2 similar proteins: A0A2R9YJI3, B2ZHY2, B3DM66, B4XF06, D4A3U0, O02777, O43194, O46635, P08909, P08911, P0C0W8, P14842, P18599, P20272, P21554, P28223, P28335, P32240, P34311, P34968, P35363, P47746, P50128, P50129, P56971, P70259, Q09502, Q333S9, Q5IS53, Q5IS66, Q5IS73, Q5IS98, Q5R4Q6, Q5U431, Q60F97, Q6DWJ6, Q71SP5, Q75Z89, Q801M1, Q80UC8

Diamond homologs: A0A2R9YJI3, D4A3U0, Q8BZL4, Q99680

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

344 predictions. Top by Δscore:

Variant	Effect	Δscore
7:107471370:A:G	acceptor_gain	1.0000
7:107470443:GAG:G	donor_gain	0.9900
7:107471367:ACAAG:A	acceptor_gain	0.9900
7:107471369:A:AG	acceptor_gain	0.9900
7:107471369:AAG:A	acceptor_gain	0.9900
7:107471369:AAGG:A	acceptor_gain	0.9900
7:107471511:GGAA:G	donor_gain	0.9900
7:107474033:A:AG	acceptor_gain	0.9900
7:107474034:G:GG	acceptor_gain	0.9900
7:107470442:AGAGG:A	donor_loss	0.9800
7:107470444:AGG:A	donor_loss	0.9800
7:107470446:G:GC	donor_loss	0.9800
7:107470447:T:A	donor_loss	0.9800
7:107474029:TTCTA:T	acceptor_loss	0.9800
7:107474030:TCTA:T	acceptor_loss	0.9800
7:107474031:CTA:C	acceptor_loss	0.9800
7:107474032:TAGGG:T	acceptor_loss	0.9800
7:107474033:A:C	acceptor_loss	0.9800
7:107471367:A:AG	acceptor_gain	0.9700
7:107471368:C:G	acceptor_gain	0.9700
7:107474033:AG:A	acceptor_gain	0.9700
7:107474034:GG:G	acceptor_gain	0.9700
7:107474080:T:TA	acceptor_gain	0.9700
7:107470446:G:GG	donor_gain	0.9600
7:107472059:T:G	acceptor_gain	0.9600
7:107474034:GGGA:G	acceptor_gain	0.9500
7:107471498:GAGT:G	donor_gain	0.9400
7:107471755:G:GT	donor_gain	0.9400
7:107474575:T:A	donor_gain	0.9400
7:107471370:AG:A	acceptor_gain	0.9300

AlphaMissense

2845 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:107474223:G:A	G55R	0.999
7:107474223:G:C	G55R	0.999
7:107474224:G:A	G55E	0.999
7:107474232:A:C	S58R	0.999
7:107474234:C:A	S58R	0.999
7:107474234:C:G	S58R	0.999
7:107474311:T:C	L84P	0.999
7:107474323:A:C	D88A	0.999
7:107474323:A:T	D88V	0.999
7:107475024:T:C	F322L	0.999
7:107475026:T:A	F322L	0.999
7:107475026:T:G	F322L	0.999
7:107475036:T:A	W326R	0.999
7:107475036:T:C	W326R	0.999
7:107475043:C:G	P328R	0.999
7:107475151:C:A	P364H	0.999
7:107475151:C:G	P364R	0.999
7:107474237:C:A	N59K	0.998
7:107474237:C:G	N59K	0.998
7:107474289:A:C	S77R	0.998
7:107474291:T:A	S77R	0.998
7:107474291:T:G	S77R	0.998
7:107474334:T:C	C92R	0.998
7:107474436:A:C	S126R	0.998
7:107474438:T:A	S126R	0.998
7:107474438:T:G	S126R	0.998
7:107474479:G:C	R140T	0.998
7:107474480:A:C	R140S	0.998
7:107474480:A:T	R140S	0.998
7:107474481:T:G	Y141D	0.998

dbSNP variants (sampled 300 via entrez): RS1000598964 (7:107469638 A>G), RS1000699137 (7:107477228 A>G), RS1000723431 (7:107476857 T>C,G), RS1000928679 (7:107469839 T>A), RS1001663807 (7:107470157 C>A,G), RS1001814651 (7:107476822 T>A), RS1002430620 (7:107469215 T>C), RS1002872265 (7:107468951 G>A), RS1004165862 (7:107471972 T>A,C), RS1004631495 (7:107478191 T>C), RS1004808754 (7:107473571 C>G), RS1004882596 (7:107471840 A>G), RS1005182852 (7:107473934 A>C), RS1005467435 (7:107470211 A>G), RS1006169838 (7:107478242 A>G)

Disease associations

OMIM: gene MIM:601910 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005956_26	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_48	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06
GCST90013406_282	Liver enzyme levels (alkaline phosphatase)	1.000000e-25

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523914 (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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression	2
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
entinostat	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Sunitinib	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	increases expression	1
Thimerosal	increases expression	1
Valproic Acid	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Thapsigargin	increases expression	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
CHEMBL4883440	Binding	PRESTO-Tango GPCRome screening (GPR22)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_LA42	PathHunter U2OS GPR22 beta-arrestin	Cancer cell line	Female

Clinical trials (associated diseases)

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