GPR61

Summary

GPR61 (G protein-coupled receptor 61, HGNC:13300) is a protein-coding gene on chromosome 1p13.3, encoding G-protein coupled receptor 61 (Q9BZJ8). Orphan G-protein coupled receptor. It is a selective cancer dependency (DepMap: 28.1% of cell lines).

This gene belongs to the G-protein coupled receptor 1 family. G protein-coupled receptors contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. The protein encoded by this gene is most closely related to biogenic amine receptors.

Source: NCBI Gene 83873 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 52 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 28.1% of screened cell lines
• MANE Select transcript: NM_001393907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13300
Approved symbol	GPR61
Name	G protein-coupled receptor 61
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	BALGR
Ensembl gene	ENSG00000156097
Ensembl biotype	protein_coding
OMIM	606916
Entrez	83873

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 nonsense_mediated_decay, 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000404129, ENST00000469383, ENST00000526744, ENST00000527748, ENST00000616874, ENST00000618721, ENST00000689084

RefSeq mRNA: 2 — MANE Select: NM_001393907 NM_001393907, NM_031936

CCDS: CCDS801

Canonical transcript exons

ENST00000527748 — 2 exons

Exon	Start	End
ENSE00001556530	109539872	109539953
ENSE00002146744	109542422	109547260

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 79.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8086 / max 105.4138, expressed in 141 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4422	0.7132	132
4423	0.0955	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	79.76	gold quality
right frontal lobe	UBERON:0002810	78.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.46	gold quality
adenohypophysis	UBERON:0002196	75.22	gold quality
pituitary gland	UBERON:0000007	74.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.55	gold quality
anterior cingulate cortex	UBERON:0009835	73.78	gold quality
cerebellar hemisphere	UBERON:0002245	73.50	gold quality
cerebellar cortex	UBERON:0002129	73.46	gold quality
frontal cortex	UBERON:0001870	72.42	gold quality
neocortex	UBERON:0001950	71.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.44	gold quality
hypothalamus	UBERON:0001898	71.42	gold quality
cerebellum	UBERON:0002037	71.23	gold quality
nucleus accumbens	UBERON:0001882	70.28	gold quality
putamen	UBERON:0001874	69.21	gold quality
adrenal tissue	UBERON:0018303	68.74	gold quality
caudate nucleus	UBERON:0001873	68.20	gold quality
right uterine tube	UBERON:0001302	67.68	gold quality
amygdala	UBERON:0001876	67.33	gold quality
cerebral cortex	UBERON:0000956	67.11	gold quality
forebrain	UBERON:0001890	67.08	gold quality
brain	UBERON:0000955	66.75	gold quality
left testis	UBERON:0004533	66.07	gold quality
right testis	UBERON:0004534	66.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.59	gold quality
right lobe of thyroid gland	UBERON:0001119	65.45	gold quality
left lobe of thyroid gland	UBERON:0001120	64.96	gold quality
thyroid gland	UBERON:0002046	64.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting GPR61, 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-6833-3P	100.00	70.63	3197
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-3928-5P	98.50	67.48	980

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• maps to chromosome 1, is widely expressed, with expression highest in the brain areas associated with cognition, learning, and memory. (PMID:11690637)
• Modeling rationalizes the effects of transmembrane proline mutants previously reported for another family of GPCR. (PMID:15615699)
• We conclude that the N-terminal domain of GPR61 is required for maintaining its constitutive activity and functions as a tethered intramolecular ligand. (PMID:19025769)
• 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

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr61	ENSDARG00000055570
mus_musculus	Gpr61	ENSMUSG00000046793
rattus_norvegicus	Gpr61	ENSRNOG00000019738

Paralogs (3): GPR176 (ENSG00000166073), GPR62 (ENSG00000180929), GPR135 (ENSG00000181619)

Protein

Protein identifiers

G-protein coupled receptor 61 — Q9BZJ8 (reviewed: Q9BZJ8)

Alternative names: Biogenic amine receptor-like G-protein coupled receptor

All UniProt accessions (3): Q9BZJ8, A0A8I5KY74, G4XH66

UniProt curated annotations — full annotation on UniProt →

Function. Orphan G-protein coupled receptor. Constitutively activates the G(s)-alpha/cAMP signaling pathway. Shows a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization. May be involved in the regulation of food intake and body weight.

Subunit / interactions. Forms heterodimer with MTNR1B. Interacts with ARRB1 and ARRB2 in a spontaneous and agonist-independent manner; leading to the internalization of GPR61 in the endosomal compartment.

Subcellular location. Cell membrane. Endosome membrane.

Tissue specificity. Expressed in brain; detected in frontal and temporal lobes, occipital pole, amygdala and hippocampus. Also expressed in testis and T cells, B cells, and monocyte. Low expression in many other tissues. Widely expressed in the hippocampus (at protein level).

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

RefSeq proteins (2): NP_001380836, NP_114142 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (42 total): helix 10, topological domain 8, transmembrane region 7, sequence conflict 7, strand 3, turn 2, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8TB7	ELECTRON MICROSCOPY	2.94
9YFU	ELECTRON MICROSCOPY	3.08
8KGK	ELECTRON MICROSCOPY	3.16
8TB0	ELECTRON MICROSCOPY	3.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZJ8-F1	69.55	0.29

Antibody-complex structures (SAbDab): 2 — 8KGK, 8TB0

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 (1): 12

Mutagenesis-validated functional residues (1):

Position	Phenotype
12	does not affect subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): RNGTGGGC_UNKNOWN, CAGCTG_AP4_Q5, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_SIGNAL_TRANSDUCTION_IN_ABSENCE_OF_LIGAND, AACTTT_UNKNOWN, GOCC_RECEPTOR_COMPLEX, GOBP_ADENYLATE_CYCLASE_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, TCANNTGAY_SREBP1_01, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, CHANGOLKAR_H2AFY_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_ARRESTIN_FAMILY_PROTEIN_BINDING

GO Biological Process (3): G protein-coupled receptor signaling pathway (GO:0007186), ligand-independent adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0038035), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), 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
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
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
protein binding	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

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR61	GPER1	Q99527	902
GPR61	RNF157	Q96PX1	487
GPR61	GPR20	Q99678	476
GPR61	GPR150	Q8NGU9	474
GPR61	GPR52	Q9Y2T5	469
GPR61	GPR162	Q16538	456
GPR61	GPR63	Q9BZJ6	454
GPR61	GPR3	P46089	452
GPR61	GPR45	Q9Y5Y3	445
GPR61	GPR82	Q96P67	439
GPR61	GPR17	Q13304	425
GPR61	GPR39	O43194	422
GPR61	RANBP10	Q6VN20	418
GPR61	PRPSAP1	Q14558	406
GPR61	SYPL2	Q5VXT5	396

IntAct

72 interactions, top by confidence:

A	B	Type	Score
TMEM60	GPR61	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	GPR61	psi-mi:“MI:0915”(physical association)	0.560
GPR61	GJA8	psi-mi:“MI:0915”(physical association)	0.560
GPR61	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
GPR61	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
PMP22	GPR61	psi-mi:“MI:0915”(physical association)	0.560
ARL6IP6	GPR61	psi-mi:“MI:0915”(physical association)	0.560
GPR61	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
TMEM147	GPR61	psi-mi:“MI:0915”(physical association)	0.560
CTXN3	GPR61	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	GPR61	psi-mi:“MI:0915”(physical association)	0.560
KLRC1	GPR61	psi-mi:“MI:0915”(physical association)	0.560
ARLN	GPR61	psi-mi:“MI:0915”(physical association)	0.560
PLP1	GPR61	psi-mi:“MI:0915”(physical association)	0.560
EMP3	GPR61	psi-mi:“MI:0915”(physical association)	0.560
GPR61	CLDND1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0B	GPR61	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	GPR61	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	GPR61	psi-mi:“MI:0915”(physical association)	0.560
GPR61	SLC12A7	psi-mi:“MI:0915”(physical association)	0.560
	GPR61	psi-mi:“MI:0915”(physical association)	0.560
GJB6	GPR61	psi-mi:“MI:0915”(physical association)	0.560
GJA8	GPR61	psi-mi:“MI:0915”(physical association)	0.560
GPR61	RAMP1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (22): GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), GPR61 (Two-hybrid), FCER1G (Two-hybrid), C4orf3 (Two-hybrid), SLC13A4 (Two-hybrid), SCN3B (Two-hybrid)

ESM2 similar proteins: A0A287A2K5, F1MV99, O08858, O43193, O77808, O97772, P28646, P30098, P30552, P30553, P30796, P30872, P30873, P30937, P30938, P31391, P32239, P32300, P32307, P32745, P33533, P35346, P35370, P35377, P41143, P41146, P46095, P46627, P47748, P48044, P49660, P51651, P56481, P58406, P79266, P79292, Q49LX5, Q5D0K2, Q6W5G4, Q6YNI2

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

822 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109539949:CAAAG:C	donor_loss	0.9500
1:109539950:AAAGG:A	donor_loss	0.9500
1:109539951:AAG:A	donor_loss	0.9500
1:109539952:AG:A	donor_loss	0.9500
1:109539953:GG:G	donor_loss	0.9500
1:109543177:T:A	acceptor_gain	0.9500
1:109544339:C:G	donor_gain	0.9500
1:109544397:G:GT	donor_gain	0.9500
1:109543856:G:GT	donor_gain	0.9400
1:109544329:T:G	donor_gain	0.9400
1:109544400:GGA:G	donor_gain	0.9400
1:109543168:T:TA	acceptor_gain	0.9100
1:109544045:T:G	acceptor_gain	0.9000
1:109544045:T:TA	acceptor_gain	0.8900
1:109544332:C:A	donor_gain	0.8900
1:109542927:G:GT	donor_gain	0.8800
1:109543168:T:G	acceptor_gain	0.8800
1:109543174:T:TA	acceptor_gain	0.8700
1:109544044:AT:A	acceptor_gain	0.8600
1:109544369:G:GT	donor_gain	0.8500
1:109544044:ATG:A	acceptor_gain	0.8400
1:109544401:G:T	donor_gain	0.8400
1:109545309:A:AG	acceptor_gain	0.8400
1:109545310:G:GG	acceptor_gain	0.8400
1:109543453:T:TA	donor_gain	0.8300
1:109543454:A:AA	donor_gain	0.8300
1:109543167:AT:A	acceptor_gain	0.8100
1:109545310:GGACT:G	acceptor_gain	0.8100
1:109539954:GT:G	donor_gain	0.7900
1:109539955:T:A	donor_gain	0.7900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001013342 (1:109541155 T>C), RS1001211076 (1:109544679 C>T), RS1002186344 (1:109537872 C>A), RS1002658653 (1:109546580 C>T), RS1002888054 (1:109546593 T>A,G), RS1003825607 (1:109540590 T>C), RS1003837881 (1:109538951 C>A), RS1003905416 (1:109538546 C>T), RS1004199285 (1:109540847 A>G), RS1004518331 (1:109539196 T>G), RS1004538806 (1:109546529 G>C), RS1004772938 (1:109546473 G>A), RS1005148468 (1:109546072 C>T), RS1005488864 (1:109544106 C>A), RS1005581343 (1:109540024 C>A)

Disease associations

OMIM: gene MIM:606916 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001840_10	Stearic acid (18:0) levels	5.000000e-06
GCST003177_33	Childhood body mass index	5.000000e-08
GCST003177_34	Childhood body mass index	5.000000e-08
GCST003944_10	Hepcidin/ferritin ratio	3.000000e-07
GCST003944_11	Hepcidin/ferritin ratio	4.000000e-06
GCST004065_77	Waist circumference	3.000000e-09
GCST004065_81	Waist circumference	1.000000e-09
GCST004557_77	Body mass index	2.000000e-10
GCST004558_123	Body mass index (joint analysis main effects and physical activity interaction)	6.000000e-06
GCST004559_178	Body mass index in physically active individuals	3.000000e-09
GCST007565_161	Morning person	4.000000e-14
GCST007576_307	Chronotype	1.000000e-07
GCST007576_39	Chronotype	4.000000e-14
GCST010988_249	Adult body size	4.000000e-23
GCST010989_179	Body size at age 10	5.000000e-28
GCST012299_20	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	4.000000e-07

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007901	hepcidin:ferritin ratio
EFO:0008002	physical activity measurement
EFO:0008328	chronotype measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523918 (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 emerging pharmacology

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 1 [PMID: 37741852]	Inverse agonist	8.0	pIC50

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
kojic acid	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Lipopolysaccharides	increases expression, affects response to substance	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	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
CHEMBL4883460	Binding	PRESTO-Tango GPCRome screening (GPR61)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX69	PathHunter CHO-K1 GPR61 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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