GPR62

Summary

GPR62 (G protein-coupled receptor 62, HGNC:13301) is a protein-coding gene on chromosome 3p21.2, encoding G-protein coupled receptor 62 (Q9BZJ7). Orphan G-protein coupled receptor.

Enables arrestin family protein binding activity. Involved in ligand-independent adenylate cyclase-activating G protein-coupled receptor signaling pathway and positive regulation of calcium-mediated signaling. Located in endosome and plasma membrane. Part of receptor complex.

Source: NCBI Gene 118442 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• MANE Select transcript: NM_080865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13301
Approved symbol	GPR62
Name	G protein-coupled receptor 62
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180929
Ensembl biotype	protein_coding
OMIM	606917
Entrez	118442

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000322241

RefSeq mRNA: 1 — MANE Select: NM_080865 NM_080865

CCDS: CCDS2838

Canonical transcript exons

ENST00000322241 — 1 exons

Exon	Start	End
ENSE00001224327	51955381	51957499

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 86.37.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5518 / max 64.2367, expressed in 78 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36792	0.4300	75
36793	0.1218	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	86.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.95	gold quality
spinal cord	UBERON:0002240	85.44	gold quality
medial globus pallidus	UBERON:0002477	82.23	gold quality
subthalamic nucleus	UBERON:0001906	81.97	gold quality
globus pallidus	UBERON:0001875	81.62	gold quality
endothelial cell	CL:0000115	79.59	silver quality
ventral tegmental area	UBERON:0002691	79.46	gold quality
dorsal plus ventral thalamus	UBERON:0001897	78.48	gold quality
corpus callosum	UBERON:0002336	77.49	gold quality
midbrain	UBERON:0001891	77.39	gold quality
substantia nigra	UBERON:0002038	77.27	gold quality
lateral globus pallidus	UBERON:0002476	76.85	gold quality
medulla oblongata	UBERON:0001896	75.50	gold quality
putamen	UBERON:0001874	75.18	gold quality
Ammon’s horn	UBERON:0001954	75.02	gold quality
substantia nigra pars reticulata	UBERON:0001966	73.93	silver quality
superior vestibular nucleus	UBERON:0007227	73.91	gold quality
prefrontal cortex	UBERON:0000451	73.51	gold quality
lateral nuclear group of thalamus	UBERON:0002736	72.90	silver quality
Brodmann (1909) area 9	UBERON:0013540	72.24	gold quality
hypothalamus	UBERON:0001898	71.85	gold quality
pons	UBERON:0000988	71.74	gold quality
amygdala	UBERON:0001876	71.38	gold quality
substantia nigra pars compacta	UBERON:0001965	70.69	silver quality
caudate nucleus	UBERON:0001873	70.59	gold quality
Brodmann (1909) area 46	UBERON:0006483	70.34	gold quality
temporal lobe	UBERON:0001871	69.77	gold quality
sperm	CL:0000019	69.75	gold quality
frontal cortex	UBERON:0001870	69.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting GPR62, 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-9902	99.89	69.15	2250
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-6773-5P	97.04	64.30	595

Literature-anchored findings (GeneRIF, showing 1)

• Collectively, these data show that GPR61, GPR62 and GPR135 are unable to bind melatonin, but show a reciprocal regulatory interaction with MT2 receptors. (PMID:28827538)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gpr62	ENSMUSG00000091735
rattus_norvegicus	Gpr62	ENSRNOG00000083309

Paralogs (3): GPR61 (ENSG00000156097), GPR176 (ENSG00000166073), GPR135 (ENSG00000181619)

Protein

Protein identifiers

G-protein coupled receptor 62 — Q9BZJ7 (reviewed: Q9BZJ7)

Alternative names: G-protein coupled receptor GPCR8, G-protein coupled receptor KPG_005

All UniProt accessions (1): Q9BZJ7

UniProt curated annotations — full annotation on UniProt →

Function. Orphan G-protein coupled receptor. Constitutively activates the G(q/11)/inositol phosphate and the G(s)-alpha/cAMP signaling pathways. Has spontaneous activity for beta-arrestin recruitment. Shows a reciprocal modulation of signaling functions with the melatonin receptor MTNR1B most likely through receptor heteromerization.

Subunit / interactions. Homodimers. Forms heterodimer with MTNR1B. Interacts with ARRB1 and ARRB2 in a spontaneous and agonist-independent manner; leading to the internalization of GPR62 in the endosomal compartment.

Subcellular location. Cell membrane. Endosome membrane.

Tissue specificity. Expressed in brain; detected in the basal forebrain, frontal cortex, caudate, putamen, thalamus and hippocampus.

Domain organisation. Lacks the conserved DRY and BBXXB motifs. The restoration of these motifs affects its constitutive activity.

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

RefSeq proteins (1): NP_543141* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (22 total): topological domain 8, transmembrane region 7, sequence variant 3, glycosylation site 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZJ7-F1	76.66	0.35

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): 3, 8

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_SIGNAL_TRANSDUCTION_IN_ABSENCE_OF_LIGAND, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOCC_RECEPTOR_COMPLEX, GOBP_ADENYLATE_CYCLASE_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, HEB_Q6, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, MARTENS_TRETINOIN_RESPONSE_DN

GO Biological Process (5): G protein-coupled receptor signaling pathway (GO:0007186), ligand-independent adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0038035), positive regulation of calcium-mediated signaling (GO:0050850), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189)

GO Molecular Function (4): G protein-coupled receptor activity (GO:0004930), identical protein binding (GO:0042802), arrestin family protein binding (GO:1990763), protein binding (GO:0005515)

GO Cellular Component (5): endosome (GO:0005768), plasma membrane (GO:0005886), endosome membrane (GO:0010008), signaling receptor complex (GO:0043235), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
signal transduction in absence of ligand	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
positive regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

830 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR62	GPER1	Q99527	909
GPR62	GPR135	Q8IZ08	634
GPR62	GPR26	Q8NDV2	582
GPR62	GPR162	Q16538	557
GPR62	GPR52	Q9Y2T5	524
GPR62	GPR25	O00155	509
GPR62	GPR50	Q13585	497
GPR62	GPR82	Q96P67	491
GPR62	GPR101	Q96P66	487
GPR62	GPR3	P46089	474
GPR62	GPR87	Q9BY21	473
GPR62	GPR45	Q9Y5Y3	468
GPR62	GPR20	Q99678	464
GPR62	GPR39	O43194	448
GPR62	GPR150	Q8NGU9	432

IntAct

7 interactions, top by confidence:

A	B	Type	Score
	GPR62	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	GPR62	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR62	psi-mi:“MI:0915”(physical association)	0.400
GPR62	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR62	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: F2Z333, O00155, O43193, O54897, O60755, O77808, O88626, O88721, O88853, O95977, P21917, P30518, P32307, P34995, P35375, P46095, P48044, P50406, P51436, P51651, P70597, Q00788, Q5E9H8, Q5IS65, Q684M3, Q6NV75, Q6PI62, Q6TLJ0, Q6YNI2, Q7TQN7, Q7TQP2, Q80UC6, Q862A8, Q862A9, Q8BGE9, Q8HYC3, Q8IZ08, Q91X56, Q96P69, Q9BGL8

Diamond homologs: P50406, Q5IS65, Q80UC6, Q8C010, Q91178, Q9BZJ7, Q9BZJ8, O02664, O73810, O77408, P14416, P20288, P21917, P24628, P28285, P28286, P30546, P30729, P31389, P31390, P34973, P46095, P52702, P53453, P60026, P61168, P61169, P70174, Q17232, Q25188, Q25414, Q4LBB6, Q6TLI9, Q86ME6, Q9GJU1, Q9R1C8, E7EM37, O42384, O42385, O70432

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

107 predictions. Top by Δscore:

Variant	Effect	Δscore
3:51955398:GGGC:G	donor_gain	0.9100
3:51955399:GGC:G	donor_gain	0.7300
3:51955400:GC:G	donor_gain	0.6900
3:51955401:C:G	donor_gain	0.6400
3:51955581:A:AG	donor_gain	0.5700
3:51957028:TGAAA:T	acceptor_gain	0.5200
3:51955539:G:GT	donor_gain	0.3700
3:51955579:TG:T	donor_gain	0.3700
3:51956314:A:T	donor_gain	0.3700
3:51956518:T:G	donor_gain	0.3700
3:51956519:G:GG	donor_gain	0.3700
3:51957022:G:GT	acceptor_gain	0.3700
3:51956460:G:GT	donor_gain	0.3600
3:51956524:G:T	donor_gain	0.3600
3:51956523:GGGC:G	donor_gain	0.3400
3:51956607:C:T	donor_gain	0.3400
3:51957010:TCCAG:T	acceptor_gain	0.3400
3:51957011:CCAGC:C	acceptor_gain	0.3400
3:51957119:GGGCA:G	acceptor_gain	0.3400
3:51955565:GAGCA:G	donor_gain	0.3300
3:51956363:C:T	donor_gain	0.3300
3:51957136:CAG:C	acceptor_gain	0.3300
3:51955397:GGGGC:G	donor_gain	0.3200
3:51956313:G:GT	donor_gain	0.3200
3:51957138:G:T	acceptor_gain	0.3200
3:51957201:A:T	donor_gain	0.3200
3:51955582:T:G	donor_gain	0.3100
3:51957096:C:CT	acceptor_gain	0.3100
3:51955580:G:A	donor_gain	0.3000
3:51955626:AGCG:A	acceptor_gain	0.3000

AlphaMissense

2222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:51956400:T:C	F250L	0.992
3:51956402:T:A	F250L	0.992
3:51956402:T:G	F250L	0.992
3:51956395:G:A	G248D	0.989
3:51956499:T:C	F283L	0.989
3:51956501:C:A	F283L	0.989
3:51956501:C:G	F283L	0.989
3:51956401:T:G	F250C	0.987
3:51955748:C:A	N32K	0.985
3:51955748:C:G	N32K	0.985
3:51956401:T:C	F250S	0.985
3:51955965:G:A	G105R	0.984
3:51955965:G:C	G105R	0.984
3:51956203:C:A	P184H	0.984
3:51956082:G:C	G144R	0.983
3:51956193:T:C	F181L	0.983
3:51956195:C:A	F181L	0.983
3:51956195:C:G	F181L	0.983
3:51956419:C:A	P256H	0.982
3:51956061:T:A	W137R	0.981
3:51956061:T:C	W137R	0.981
3:51956394:G:C	G248R	0.981
3:51956203:C:G	P184R	0.979
3:51956500:T:C	F283S	0.979
3:51956512:C:A	P287H	0.979
3:51956481:T:A	W277R	0.978
3:51956481:T:C	W277R	0.978
3:51956488:C:A	A279D	0.977
3:51956412:T:A	W254R	0.975
3:51956412:T:C	W254R	0.975

dbSNP variants (sampled 300 via entrez): RS1000238463 (3:51954372 T>A,G), RS1000651797 (3:51957116 G>A,T), RS1001217335 (3:51957657 G>T), RS1001722755 (3:51956435 C>A), RS1001776841 (3:51956219 C>A,T), RS1002056785 (3:51957968 G>C), RS1003581071 (3:51957913 T>C,G), RS1003897872 (3:51953558 C>A,G), RS1003973149 (3:51954013 G>A), RS1005409188 (3:51954926 C>T), RS1005693780 (3:51955244 C>T), RS1007311295 (3:51957496 A>C,G), RS1008205531 (3:51953498 C>A,T), RS1009801481 (3:51954788 T>G), RS1009875490 (3:51955147 G>A,C)

Disease associations

OMIM: gene MIM:606917 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523917 (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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Valproic Acid	increases methylation	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
CHEMBL4883461	Binding	PRESTO-Tango GPCRome screening (GPR62)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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