GPR3

Summary

GPR3 (G protein-coupled receptor 3, HGNC:4484) is a protein-coding gene on chromosome 1p36.11, encoding G-protein coupled receptor 3 (P46089). Constitutively active G-protein coupled receptor that maintains high cAMP levels and contributes to several processes, including meiotic arrest in oocytes and neuronal development, through activation of intracellular signaling pathways.

This gene is a member of the G protein-coupled receptor family and is found in the cell membrane. G protein-coupled receptors, characterized by a seven transmembrane domain motif, are involved in translating outside signals into G protein mediated intracellular effects. The encoded protein activates adenylate cyclase and modulates amyloid-beta production in a mouse model, suggesting that it may play a role in Alzheimer’s disease.

Source: NCBI Gene 2827 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• Druggable target: yes
• MANE Select transcript: NM_005281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4484
Approved symbol	GPR3
Name	G protein-coupled receptor 3
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	ACCA
Ensembl gene	ENSG00000181773
Ensembl biotype	protein_coding
OMIM	600241
Entrez	2827

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000374024, ENST00000924879

RefSeq mRNA: 1 — MANE Select: NM_005281 NM_005281

CCDS: CCDS303

Canonical transcript exons

ENST00000374024 — 2 exons

Exon	Start	End
ENSE00001462185	27393794	27395814
ENSE00003992008	27392622	27392737

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 84.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.1062 / max 28.7448, expressed in 926 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1709	1.4709	755
1708	0.6352	358

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	84.55	gold quality
secondary oocyte	CL:0000655	75.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.00	gold quality
prefrontal cortex	UBERON:0000451	72.94	gold quality
frontal pole	UBERON:0002795	72.27	gold quality
paraflocculus	UBERON:0005351	71.76	gold quality
cingulate cortex	UBERON:0003027	71.54	gold quality
middle frontal gyrus	UBERON:0002702	71.47	gold quality
anterior cingulate cortex	UBERON:0009835	71.39	gold quality
oocyte	CL:0000023	71.01	gold quality
right frontal lobe	UBERON:0002810	70.48	gold quality
frontal cortex	UBERON:0001870	69.43	gold quality
neocortex	UBERON:0001950	69.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.64	gold quality
islet of Langerhans	UBERON:0000006	68.38	gold quality
primary visual cortex	UBERON:0002436	68.10	gold quality
right atrium auricular region	UBERON:0006631	67.98	gold quality
cerebellar cortex	UBERON:0002129	67.75	gold quality
cerebellar hemisphere	UBERON:0002245	67.66	gold quality
triceps brachii	UBERON:0001509	67.23	gold quality
tongue squamous epithelium	UBERON:0006919	67.21	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.19	gold quality
gluteal muscle	UBERON:0002000	67.10	gold quality
stromal cell of endometrium	CL:0002255	66.93	gold quality
granulocyte	CL:0000094	66.82	gold quality
cerebellum	UBERON:0002037	66.63	gold quality
cardiac atrium	UBERON:0002081	66.63	gold quality
hypothalamus	UBERON:0001898	66.21	gold quality
cerebral cortex	UBERON:0000956	66.15	gold quality
adenohypophysis	UBERON:0002196	66.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting GPR3, 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-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-10393-5P	99.65	68.01	1368

Literature-anchored findings (GeneRIF, showing 12)

• control of gene expression in vascular endothelial cells in the presence of fluid shear stress and classifies it as a sphingosine 1-phosphate receptor. (PMID:12649592)
• GPR3 is expressed in the ovary and testes, and is necessary for the regulation of meiosis in mouse. (PMID:15591206)
• We conclude that perturbations in GPR3 are not a common explanation for POF in this population. (PMID:17953967)
• Mutations in GPR3 are not a common cause of premature ovarian failure in Chinese women. (PMID:20158988)
• GPR3 is a key factor in the regulation of the nervous system and follicle development.[review] (PMID:23732663)
• Results demonstrate that GPR3 signals at the plasma membrane and can be silenced by GRK2/beta-arrestin overexpression. These results also strongly implicate the serine and/or threonine residues in the third intracellular loop in the regulation of GPR3 activity. (PMID:23826079)
• Gpr3 stimulates Abeta production via interactions with APP and beta-arrestin2. (PMID:24069330)
• these results suggest an important role of the allosteric sodium binding site for GPR3 activity and open a possible avenue for the modulation of Abeta production in the Alzheimer’s Disease. (PMID:30038319)
• Development of a High-Throughput Screening-Compatible Assay for Discovery of GPR3 Inverse Agonists Using a cAMP Biosensor. (PMID:31516076)
• Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis. (PMID:34048700)
• Silencing the G-protein coupled receptor 3-salt inducible kinase 2 pathway promotes human beta cell proliferation. (PMID:34302056)
• Rare variants in GPR3 in POI patients: a case series with review of literature. (PMID:37919810)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gpr3	ENSMUSG00000049649
rattus_norvegicus	Gpr3	ENSRNOG00000009540

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), S1PR5 (ENSG00000180739), MC2R (ENSG00000185231), CNR2 (ENSG00000188822), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

G-protein coupled receptor 3 — P46089 (reviewed: P46089)

Alternative names: ACCA orphan receptor

All UniProt accessions (2): P46089, F1DAM5

UniProt curated annotations — full annotation on UniProt →

Function. Constitutively active G-protein coupled receptor that maintains high cAMP levels and contributes to several processes, including meiotic arrest in oocytes and neuronal development, through activation of intracellular signaling pathways. Essential activator of thermogenic adipocytes, where it drives thermogenesis via constitutive G(s)-coupling activity in the absence of ligand. May be activated by lipid-derived agonists such as oleoylethanolamide (OEA), oleic acid or sphingosine 1-phosphate leading to activation of the G(s)/cAMP/PKA signaling pathway. Plays a potential role in modulating brain functions, including behavioral responses to stress and amyloid-beta peptide generation in neurons. Stimulates neurite outgrowth in cerebellar granule neurons via PKA, ERK, and PI3K-mediated signaling pathways.

Subunit / interactions. Homodimer. Interacts with GNAS.

Subcellular location. Cell membrane.

Tissue specificity. Expressed predominantly in the central nervous system, and at low levels in the lung, kidney, testis, ovary and eye. Highly expressed in regions of the brain implicated in the Alzheimer disease.

Activity regulation. GPR3 bound to the lipid agonist is in an equilibrium between monomeric and dimeric states. G protein engagement leads to dissociation of the dimer, and efficient coupling and signaling of the G(s) protein.

Induction. Upon cold exposure by a lipolytic signal in thermogenic adipose tissue.

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

RefSeq proteins (1): NP_005272* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000723	GPR_3/6/12_orphan	Family
IPR000984	GPR3	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (43 total): helix 10, topological domain 8, transmembrane region 7, mutagenesis site 4, strand 4, modified residue 3, turn 2, chain 1, lipid moiety-binding region 1, glycosylation site 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8WW2	ELECTRON MICROSCOPY	2.79
8X2K	ELECTRON MICROSCOPY	3.03
9LYC	ELECTRON MICROSCOPY	3.06
9LYB	ELECTRON MICROSCOPY	3.16
9M8P	ELECTRON MICROSCOPY	3.42
8U8F	ELECTRON MICROSCOPY	3.49
9LYD	ELECTRON MICROSCOPY	3.66
9M8V	ELECTRON MICROSCOPY	3.83

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46089-F1	82.13	0.57

Antibody-complex structures (SAbDab): 4 — 8WW2, 8X2K, 9LYB, 9LYC

Functional residue map

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

Post-translational modifications (4): 324, 326, 328, 313

Disulfide bonds (1): 177–184

Glycosylation sites (1): 20

Mutagenesis-validated functional residues (4):

Position	Phenotype
135	partial loss of constitutive homodimerization.
211	partial loss of constitutive homodimerization.
215	partial loss of constitutive homodimerization.
280	reduced receptor activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 190 (showing top): ATF_B, MORF_FLT1, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_NUCLEAR_DIVISION, LFA1_Q6, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_SPHINGOLIPID_MEDIATED_SIGNALING_PATHWAY, MODULE_64, AAGCCAT_MIR135A_MIR135B, CREBP1_Q2, MODULE_16, CACCAGC_MIR138, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, SP1_Q2_01, CEBPB_01

GO Biological Process (6): adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), regulation of meiotic nuclear division (GO:0040020), positive regulation of cold-induced thermogenesis (GO:0120162), sphingosine-1-phosphate receptor signaling pathway (GO:0003376), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), sphingosine-1-phosphate receptor activity (GO:0038036), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
cellular anatomical structure	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
regulation of cell cycle process	1
regulation of meiotic cell cycle	1
regulation of nuclear division	1
meiotic nuclear division	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
sphingolipid mediated signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
transmembrane signaling receptor activity	1
sphingosine-1-phosphate receptor signaling pathway	1
bioactive lipid receptor activity	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

701 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR3	ARRB2	P32121	886
GPR3	GPR18	Q14330	716
GPR3	GPR55	Q9Y2T6	669
GPR3	ARRB1	P49407	610
GPR3	PDE3A	Q14432	593
GPR3	APH1A	Q96BI3	571
GPR3	GPR4	P46093	553
GPR3	CMKLR2	P46091	512
GPR3	GPR31	O00270	495
GPR3	GPR62	Q9BZJ7	474
GPR3	GPR39	O43194	455
GPR3	GPR17	Q13304	455
GPR3	GPR87	Q9BY21	454
GPR3	GPR63	Q9BZJ6	453
GPR3	GPR61	Q9BZJ8	452

IntAct

13 interactions, top by confidence:

A	B	Type	Score
GPR3	APOD	psi-mi:“MI:0914”(association)	0.530
GPR3	APP	psi-mi:“MI:0915”(physical association)	0.520
APP	GPR3	psi-mi:“MI:0915”(physical association)	0.520
Arrb2	GPR3	psi-mi:“MI:0915”(physical association)	0.400
Arrb1	GPR3	psi-mi:“MI:0915”(physical association)	0.400
GNPAT	GPR3	psi-mi:“MI:0915”(physical association)	0.370
GPR3	RXYLT1	psi-mi:“MI:0915”(physical association)	0.370
GPR3	ZNF593	psi-mi:“MI:0915”(physical association)	0.370
GPR3	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
GPR3	ARRB2	psi-mi:“MI:0914”(association)	0.350
GPR3	App	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (13): DMWD (Affinity Capture-MS), DMWD (Affinity Capture-MS), APOD (Affinity Capture-MS), GPR3 (Affinity Capture-Western), DMWD (Affinity Capture-MS), APOD (Affinity Capture-MS), TNFRSF10B (Affinity Capture-MS), SAMM50 (Affinity Capture-MS), ACTB (Affinity Capture-MS), GPR3 (Affinity Capture-RNA), GPR3 (Two-hybrid), TMEM5 (Two-hybrid), ZNF593 (Two-hybrid)

ESM2 similar proteins: A0A287A2K5, A5A4K9, F1MV99, O08858, O43193, O97772, P28646, P30098, P30552, P30553, P30796, P30872, P30873, P30937, P30938, P31391, P32239, P32300, P33533, P33535, P35346, P35370, P35372, P35377, P41143, P41144, P41145, P41146, P42866, P46089, P46095, P46627, P47748, P51651, P56481, P58406, P79266, P79292, Q2KIP6, Q49LX5

Diamond homologs: O02213, O02662, O02667, O13076, O70528, O77621, P04761, P08483, P08908, P08909, P08911, P08912, P0DMS8, P11229, P11483, P11616, P11617, P12657, P15823, P16395, P17124, P18841, P19327, P20309, P22270, P25021, P25099, P25102, P25962, P28190, P28285, P28286, P28335, P28647, P29274, P29275, P29276, P30542, P30543, P34968

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

176 predictions. Top by Δscore:

Variant	Effect	Δscore
1:27392733:GAGCG:G	donor_gain	1.0000
1:27392734:AGCGG:A	donor_loss	1.0000
1:27392735:GCG:G	donor_gain	1.0000
1:27392738:G:GA	donor_loss	1.0000
1:27392738:G:GG	donor_gain	1.0000
1:27392739:TGA:T	donor_loss	1.0000
1:27392740:GAGTA:G	donor_loss	1.0000
1:27392734:AGCG:A	donor_gain	0.9900
1:27392735:GCGG:G	donor_gain	0.9900
1:27392736:CG:C	donor_gain	0.9900
1:27392737:GG:G	donor_gain	0.9900
1:27392741:AGTAG:A	donor_loss	0.9900
1:27393789:TGCA:T	acceptor_loss	0.9900
1:27393790:GCAGG:G	acceptor_loss	0.9900
1:27393791:CAG:C	acceptor_loss	0.9900
1:27393792:A:G	acceptor_loss	0.9900
1:27393793:G:C	acceptor_loss	0.9900
1:27393523:T:TA	acceptor_gain	0.9600
1:27393792:A:AG	acceptor_gain	0.9600
1:27393793:G:GG	acceptor_gain	0.9600
1:27393789:T:TA	acceptor_gain	0.9000
1:27393780:CCTTT:C	acceptor_loss	0.8400
1:27393781:CTTTC:C	acceptor_loss	0.8400
1:27393782:TTTCT:T	acceptor_loss	0.8400
1:27393793:GGT:G	acceptor_gain	0.8400
1:27393793:GGTA:G	acceptor_gain	0.8400
1:27393792:AG:A	acceptor_gain	0.7900
1:27393793:GG:G	acceptor_gain	0.7900
1:27393786:TCCTG:T	acceptor_loss	0.7400
1:27393787:CCTGC:C	acceptor_loss	0.7400

AlphaMissense

2081 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:27394039:A:C	S81R	0.999
1:27394041:C:A	S81R	0.999
1:27394041:C:G	S81R	0.999
1:27394055:A:T	D86V	0.998
1:27394174:A:C	S126R	0.998
1:27394176:T:A	S126R	0.998
1:27394176:T:G	S126R	0.998
1:27393972:T:A	N58K	0.997
1:27393972:T:G	N58K	0.997
1:27394055:A:C	D86A	0.997
1:27394055:A:G	D86G	0.997
1:27394165:A:C	S123R	0.997
1:27394167:C:A	S123R	0.997
1:27394167:C:G	S123R	0.997
1:27393949:G:C	G51R	0.996
1:27393950:G:A	G51D	0.996
1:27394054:G:C	D86H	0.996
1:27394056:C:A	D86E	0.996
1:27394056:C:G	D86E	0.996
1:27394066:G:C	G90R	0.996
1:27394583:C:G	P262R	0.996
1:27394279:T:A	W161R	0.995
1:27394279:T:C	W161R	0.995
1:27393970:A:C	N58H	0.994
1:27394067:G:A	G90D	0.994
1:27394087:T:C	F97L	0.994
1:27394089:T:A	F97L	0.994
1:27394089:T:G	F97L	0.994
1:27394199:G:C	R134P	0.994
1:27393970:A:T	N58Y	0.993

dbSNP variants (sampled 300 via entrez): RS1000001609 (1:27395077 C>T), RS1000185542 (1:27391837 C>A,T), RS1000404398 (1:27392187 C>G,T), RS1001409073 (1:27393284 C>T), RS1002276500 (1:27395559 A>T), RS1002306152 (1:27395263 T>A), RS1002628359 (1:27393740 C>T), RS1004271712 (1:27392645 G>T), RS1004302910 (1:27392533 G>A,T), RS1004605147 (1:27391224 C>T), RS1004637638 (1:27390868 C>T), RS1005486926 (1:27395673 G>C), RS1005871636 (1:27395897 G>A,C), RS1006403573 (1:27392592 C>T), RS1007261461 (1:27390732 T>C)

Disease associations

OMIM: gene MIM:600241 | 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): CHEMBL4523856 (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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
sphingosine 1-phosphate	Full agonist	7.7	pEC50
RTI-19318-32	Agonist	6.59	pEC50
diphenyleneiodonium chloride	Full agonist	6.0	pEC50

ChEMBL bioactivities

30 potent at pChembl≥5 of 41 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.99	Kd	102.3	nM	CHEMBL5410506
6.86	EC50	137	nM	CHEMBL5415054
6.64	EC50	230	nM	CHEMBL5425788
6.58	EC50	260	nM	CHEMBL5399736
6.56	EC50	277	nM	CHEMBL5432166
6.53	Ki	295.1	nM	CHEMBL5410506
6.52	Kd	302	nM	CHEMBL5410506
6.34	EC50	455	nM	CHEMBL5409202
6.09	EC50	816	nM	CHEMBL5427433
6.05	EC50	891.2	nM	CHEMBL5410506
6.04	EC50	921	nM	CHEMBL4302437
6.04	EC50	923	nM	CHEMBL5433034
6.03	EC50	937	nM	CHEMBL5409214
6.00	EC50	1000	nM	DIPHENYLENEIODONIUM CHLORIDE
5.90	IC50	1259	nM	CHEMBL5410506
5.89	EC50	1300	nM	CHEMBL5432982
5.88	EC50	1310	nM	CHEMBL4300174
5.87	EC50	1340	nM	CHEMBL5421637
5.85	EC50	1413	nM	CHEMBL5410506
5.82	EC50	1530	nM	CHEMBL5431176
5.72	EC50	1890	nM	CHEMBL4302860
5.52	EC50	3020	nM	CHEMBL5434234
5.47	EC50	3388	nM	CHEMBL5405597
5.41	EC50	3860	nM	CHEMBL4167328
5.35	EC50	4467	nM	CHEMBL5423734
5.35	EC50	4467	nM	CHEMBL5398023
5.29	EC50	5170	nM	DIPHENYLENEIODONIUM CHLORIDE
5.29	EC50	5100	nM	CHEMBL5405489
5.21	EC50	6120	nM	CHEMBL4173205
5.12	EC50	7600	nM	CARBAZOLE

PubChem BioAssay actives

30 with measured affinity, of 142 total; 24 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[6-[2-[7-[(4-chloro-2-propan-2-yloxyphenyl)methylamino]-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenoxy]hexylcarbamoyl]-2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoate	2021309: Binding affinity to N-terminal 3xHA/Nluc-tagged full-length wild-type human GPR3 expressed in HEK293A cells using vivazine as substrate measured for 180 mins by time-course saturation based NanoBRET assay	kd	0.1023	uM
5-fluoro-11-(trifluoromethoxy)-8-iodoniatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.1370	uM
4,5-difluoro-11-(trifluoromethoxy)-8-iodoniatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.2300	uM
5-(trifluoromethoxy)-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.2600	uM
5,11-bis(trifluoromethoxy)-8-iodoniatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.2770	uM
5-methyl-11-(trifluoromethoxy)-8-iodoniatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.4550	uM
4-fluoro-5-(trifluoromethyl)-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2,4,6,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.8160	uM
5-chloro-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.9210	uM
4,5-difluoro-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2,4,6,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.9230	uM
5-(trifluoromethyl)-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	0.9370	uM
8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2,4,6,9,11-hexaene chloride	2021323: Agonist activity at FLAG/GFP-tagged GPR3 (unknown origin)-mediated cAMP signaling in HEK293 cells using d2-cAMP as substrate preincubated for 30 mins followed by substrate addition measured after 60 mins by HTRF assay	ec50	1.0000	uM
5-(2,2,2-trifluoroethoxy)-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	1.3000	uM
5-fluoro-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	1.3100	uM
5-nitro-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	1.3400	uM
5-hexyl-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	1.5300	uM
5-methoxy-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	1.8900	uM
4-fluoro-5-methyl-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	3.0200	uM
5-[2-[2-[2-[2-[2-[7-[(4-chloro-2-propan-2-yloxyphenyl)methylamino]-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]-2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoate	2021313: Total binding affinity to N-terminal 3xHA/Nluc-tagged full-length wild-type human GPR3 expressed in HEK293A cells using furimazine as substrate measured for 3 hrs by NanoBRET assay	ec50	3.3884	uM
8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2,4,6,9,11-hexaene;trifluoromethanesulfonate	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	3.8600	uM
5-[2-[2-[2-[2-[2-[2-[2-[7-[(4-chloro-2-propan-2-yloxyphenyl)methylamino]-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]-2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoate	2021313: Total binding affinity to N-terminal 3xHA/Nluc-tagged full-length wild-type human GPR3 expressed in HEK293A cells using furimazine as substrate measured for 3 hrs by NanoBRET assay	ec50	4.4668	uM
5-[6-[3-[7-[(4-chloro-2-propan-2-yloxyphenyl)methylamino]-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl]phenoxy]hexylcarbamoyl]-2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoate	2021313: Total binding affinity to N-terminal 3xHA/Nluc-tagged full-length wild-type human GPR3 expressed in HEK293A cells using furimazine as substrate measured for 3 hrs by NanoBRET assay	ec50	4.4668	uM
dibenzothiophene 5,5-dioxide	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	5.1000	uM
5-methyl-8-iodoniatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene;trifluoromethanesulfonate	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	6.1200	uM
9H-carbazole	2012292: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	ec50	7.6000	uM

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	3
Estradiol	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	increases expression	1
manganese chloride	increases abundance, decreases expression	1
ferrous chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Camptothecin	increases expression	1
Cisplatin	increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Drugs, Chinese Herbal	decreases expression	1
Formaldehyde	decreases expression	1
Manganese	decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Tetradecanoylphorbol Acetate	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-4-phenylpyridinium	increases expression	1

ChEMBL screening assays

24 unique, capped per target: 16 binding, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883444	Binding	PRESTO-Tango GPCRome screening (GPR3)	Data for DCP probe UCSF924
CHEMBL5366025	Functional	Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay	The development of diphenyleneiodonium analogs as GPR3 agonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX55	PathHunter CHO-K1 GPR3 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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