GPR52

Summary

GPR52 (G protein-coupled receptor 52, HGNC:4508) is a protein-coding gene on chromosome 1q25.1, encoding G-protein coupled receptor 52 (Q9Y2T5). Gs-coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization.

Members of the G protein-coupled receptor (GPR) family play important roles in signal transduction from the external environment to the inside of the cell.

Source: NCBI Gene 9293 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• Druggable target: yes
• MANE Select transcript: NM_005684

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4508
Approved symbol	GPR52
Name	G protein-coupled receptor 52
Location	1q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000203737
Ensembl biotype	protein_coding
OMIM	604106
Entrez	9293

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000367685

RefSeq mRNA: 1 — MANE Select: NM_005684 NM_005684

CCDS: CCDS30941

Canonical transcript exons

ENST00000367685 — 1 exons

Exon	Start	End
ENSE00001445369	174447964	174449545

Expression profiles

Bgee: expression breadth broad, 65 present calls, max score 88.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4345 / max 90.9325, expressed in 37 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6774	0.3947	34
6773	0.0398	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.68	gold quality
bone marrow cell	CL:0002092	74.23	gold quality
mucosa of paranasal sinus	UBERON:0005030	72.77	gold quality
nucleus accumbens	UBERON:0001882	67.55	gold quality
prefrontal cortex	UBERON:0000451	64.02	gold quality
putamen	UBERON:0001874	63.74	gold quality
caudate nucleus	UBERON:0001873	62.16	gold quality
colonic epithelium	UBERON:0000397	60.89	gold quality
calcaneal tendon	UBERON:0003701	59.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.56	silver quality
Brodmann (1909) area 9	UBERON:0013540	57.01	gold quality
amniotic fluid	UBERON:0000173	55.78	gold quality
frontal cortex	UBERON:0001870	55.76	gold quality
neocortex	UBERON:0001950	54.32	gold quality
epithelium of nasopharynx	UBERON:0001951	53.54	gold quality
anterior cingulate cortex	UBERON:0009835	53.46	gold quality
tonsil	UBERON:0002372	53.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	52.71	gold quality
bone marrow	UBERON:0002371	52.45	gold quality
tendon	UBERON:0000043	52.07	gold quality
forebrain	UBERON:0001890	51.88	gold quality
right frontal lobe	UBERON:0002810	51.38	gold quality
cerebral cortex	UBERON:0000956	49.83	gold quality
adrenal tissue	UBERON:0018303	49.83	gold quality
cardia of stomach	UBERON:0001162	49.80	gold quality
brain	UBERON:0000955	49.59	gold quality
adenohypophysis	UBERON:0002196	48.28	gold quality
pituitary gland	UBERON:0000007	47.72	gold quality
gingival epithelium	UBERON:0001949	47.29	gold quality
hypothalamus	UBERON:0001898	47.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting GPR52, 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-4775	99.98	75.00	6394
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-4474-5P	94.23	67.95	568

Literature-anchored findings (GeneRIF, showing 4)

• Data show that G protein-coupled receptor 52 (Gpr52) modulates huntingtin protein (Htt) levels in the striatal cells in vitro and in vivo. (PMID:25738228)
• high-resolution structures of human GPR52 in three states: a ligand-free state, a Gs-coupled self-activation state and a potential allosteric ligand-bound state (PMID:32076264)
• beta-Arrestin-2-Dependent Mechanism of GPR52 Signaling in Frontal Cortical Neurons. (PMID:32519845)
• Targeted Proteomics Combined with Affinity Mass Spectrometry Analysis Reveals Antagonist E7 Acts As an Intracellular Covalent Ligand of Orphan Receptor GPR52. (PMID:33258587)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr52	ENSDARG00000093460
mus_musculus	Gpr52	ENSMUSG00000118401
rattus_norvegicus	Gpr52	ENSRNOG00000055673

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

G-protein coupled receptor 52 — Q9Y2T5 (reviewed: Q9Y2T5)

All UniProt accessions (2): Q9Y2T5, F2YGU0

UniProt curated annotations — full annotation on UniProt →

Function. Gs-coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization. May play a role in locomotor activity through modulation of dopamine, NMDA and ADORA2A-induced locomotor activity. These behavioral changes are accompanied by modulation of the dopamine receptor signaling pathway in striatum. Modulates HTT level via cAMP-dependent but PKA independent mechanisms throught activation of RAB39B that translocates HTT to the endoplasmic reticulum, thus avoiding proteasome degradation.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in brain, especially in striatum.

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

RefSeq proteins (1): NP_005675* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050125	GPCR_opsins	Family

Pfam: PF00001

UniProt features (47 total): helix 14, topological domain 8, sequence conflict 8, transmembrane region 7, glycosylation site 3, turn 3, strand 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6LI0	X-RAY DIFFRACTION	2.2
8HMP	ELECTRON MICROSCOPY	2.77
6LI2	X-RAY DIFFRACTION	2.8
6LI1	X-RAY DIFFRACTION	2.9
6LI3	ELECTRON MICROSCOPY	3.32
9IJS	ELECTRON MICROSCOPY	3.64
9IJR	ELECTRON MICROSCOPY	3.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2T5-F1	81.87	0.50

Antibody-complex structures (SAbDab): 4 — 6LI3, 8HMP, 9IJR, 9IJS

Functional residue map

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

Disulfide bonds (1): 114–193

Glycosylation sites (3): 2, 13, 20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): GOBP_BEHAVIOR, GCANCTGNY_MYOD_Q6, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, TGACCTY_ERR1_Q2, GOBP_RESPONSE_TO_RADIATION, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, AACTTT_UNKNOWN, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, PPARA_01, GOBP_CELLULAR_RESPONSE_TO_RADIATION, GOBP_RESPONSE_TO_LIGHT_STIMULUS, TGACCTTG_SF1_Q6

GO Biological Process (7): G protein-coupled receptor signaling pathway (GO:0007186), phototransduction (GO:0007602), locomotory behavior (GO:0007626), response to xenobiotic stimulus (GO:0009410), cellular response to light stimulus (GO:0071482), signal transduction (GO:0007165), detection of visible light (GO:0009584)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), G protein-coupled photoreceptor activity (GO:0008020), protein binding (GO:0005515)

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	2
signal transduction	2
detection of light stimulus	2
behavior	1
response to chemical	1
response to light stimulus	1
cellular response to radiation	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
detection of visible light	1
photoreceptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR52	GPR88	Q9GZN0	742
GPR52	RHO	P08100	724
GPR52	GPR6	P46095	610
GPR52	GPR62	Q9BZJ7	524
GPR52	GPR158	Q5T848	513
GPR52	GPR63	Q9BZJ6	491
GPR52	GPR82	Q96P67	490
GPR52	GPR150	Q8NGU9	486
GPR52	SUCLG2	Q96I99	477
GPR52	GPR61	Q9BZJ8	469
GPR52	GPR139	Q6DWJ6	461
GPR52	GPR162	Q16538	456
GPR52	GPR85	P60893	450
GPR52	GPR20	Q99678	446
GPR52	MTNR1A	P48039	437

IntAct

8 interactions, top by confidence:

A	B	Type	Score
GPR52	ATN1	psi-mi:“MI:0915”(physical association)	0.560
GPR52	SYNGR2	psi-mi:“MI:0914”(association)	0.530
POT1	GPR52	psi-mi:“MI:0915”(physical association)	0.370
GPR52	GPR89A	psi-mi:“MI:0914”(association)	0.350
GPR52	SURF4	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): MBOAT7 (Affinity Capture-MS), SYNGR2 (Affinity Capture-MS), ALG8 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), SLC4A2 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), FITM2 (Affinity Capture-MS), FZD2 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), GPR89A (Affinity Capture-MS), EBP (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), REEP5 (Affinity Capture-MS), GJA1 (Affinity Capture-MS), CHPT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A678XMK4, A6QLE7, G3M4F8, O08890, O42384, O42574, O70528, P07550, P0C5J4, P10608, P17124, P18762, P25021, P25102, P28221, P28222, P28334, P28564, P28565, P28566, P30939, P30940, P35404, P35406, P46636, P47747, P56496, P60020, P60021, P61752, P79748, P97288, Q02284, Q0EAB5, Q13639, Q28044, Q28509, Q588Y6, Q61224, Q62758

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, A6QLE7, D4A7K7, E7FEL0, E9QJ73, O00254, O08675, O46685, P0C0W8, P0C5J4, P32246, P32249, P32250, P34996, P35366, P35383, P41231, P41232, P46093, P47900, P48042, P49650, P49651, P49652, P50132, P56482, P58826, P59902, P79928, P97266, Q149R9, Q15743, Q1JQB3, Q2Y2P0, Q3U6B2, Q3ZC80, Q4G072, Q4KLH9, Q5E9H8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

428 predictions. Top by Δscore:

Variant	Effect	Δscore
1:174448308:ATTGT:A	acceptor_gain	0.8300
1:174448308:ATT:A	acceptor_gain	0.7800
1:174448309:T:G	acceptor_gain	0.7400
1:174448312:T:TA	acceptor_gain	0.7400
1:174448320:T:A	acceptor_gain	0.7200
1:174448282:G:T	donor_gain	0.7100
1:174448293:T:G	donor_gain	0.7100
1:174449063:A:AG	acceptor_gain	0.6700
1:174449064:G:GG	acceptor_gain	0.6700
1:174448282:G:GT	donor_gain	0.6500
1:174448246:G:GA	donor_gain	0.6400
1:174448310:T:A	acceptor_gain	0.6400
1:174448169:AAT:A	donor_gain	0.6300
1:174448972:A:AG	acceptor_gain	0.6300
1:174448973:G:GG	acceptor_gain	0.6300
1:174448219:G:GA	donor_gain	0.6200
1:174448786:C:G	acceptor_gain	0.6200
1:174448747:T:G	acceptor_gain	0.6100
1:174448788:T:G	acceptor_gain	0.6100
1:174448308:A:AG	acceptor_gain	0.6000
1:174448206:GCCAC:G	donor_gain	0.5900
1:174448649:T:A	acceptor_gain	0.5900
1:174448747:T:TA	acceptor_gain	0.5900
1:174448787:A:AG	acceptor_gain	0.5900
1:174448793:A:AG	acceptor_gain	0.5900
1:174448218:T:TA	donor_gain	0.5800
1:174448913:T:G	donor_gain	0.5800
1:174448799:T:TA	acceptor_gain	0.5700
1:174448645:T:TA	acceptor_gain	0.5600
1:174448908:T:G	donor_gain	0.5600

AlphaMissense

2379 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:174448382:G:A	G91R	0.999
1:174448382:G:C	G91R	0.999
1:174448383:G:A	G91E	0.999
1:174448517:A:C	S136R	0.999
1:174448519:T:A	S136R	0.999
1:174448519:T:G	S136R	0.999
1:174448527:G:C	R139P	0.999
1:174448931:T:C	F274L	0.999
1:174448933:T:A	F274L	0.999
1:174448933:T:G	F274L	0.999
1:174448950:C:G	P280R	0.999
1:174449039:A:C	S310R	0.999
1:174449041:T:A	S310R	0.999
1:174449041:T:G	S310R	0.999
1:174448280:G:A	G57R	0.998
1:174448280:G:C	G57R	0.998
1:174448285:T:A	N58K	0.998
1:174448285:T:G	N58K	0.998
1:174448370:G:C	D87H	0.998
1:174448371:A:C	D87A	0.998
1:174448371:A:G	D87G	0.998
1:174448371:A:T	D87V	0.998
1:174448372:T:A	D87E	0.998
1:174448372:T:G	D87E	0.998
1:174448374:T:C	L88P	0.998
1:174448487:A:C	S126R	0.998
1:174448489:T:A	S126R	0.998
1:174448489:T:G	S126R	0.998
1:174448506:T:C	L132P	0.998
1:174448607:T:A	W166R	0.998

dbSNP variants (sampled 300 via entrez): RS1000118000 (1:174446299 G>A,C), RS1000905014 (1:174449922 A>C,G), RS1003125843 (1:174446585 T>G), RS1003635851 (1:174449259 A>G), RS1003925962 (1:174449577 T>G), RS1005150887 (1:174449231 C>T), RS1006360234 (1:174447649 A>C), RS1006517472 (1:174447294 T>C), RS1007673926 (1:174446698 G>A,T), RS1009247408 (1:174447118 TA>T), RS1010934245 (1:174449621 A>C,G), RS1011807622 (1:174446131 T>A), RS1012207117 (1:174449532 T>C), RS1012561190 (1:174446987 G>A), RS1012692369 (1:174446619 A>G)

Disease associations

OMIM: gene MIM:604106 | 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): CHEMBL3297639 (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 only surrogate ligands

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
derivative 17 [Nakahata et al., 2018]	Agonist	7.68	pEC50
NXE0041178	Agonist	7.56	pEC50
compound 7a [PMID: 24884590]	Agonist	7.55	pEC50
comp-43	Antagonist	6.2	pIC50

ChEMBL bioactivities

388 potent at pChembl≥5 of 389 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.97	EC50	1.06	nM	CHEMBL4852000
8.96	EC50	1.1	nM	CHEMBL4846914
8.96	EC50	1.1	nM	CHEMBL4872227
8.96	EC50	1.1	nM	CHEMBL4865057
8.96	EC50	1.1	nM	CHEMBL4869139
8.96	EC50	1.1	nM	CHEMBL4868643
8.96	EC50	1.1	nM	CHEMBL4858187
8.96	EC50	1.1	nM	CHEMBL4878069
8.96	EC50	1.1	nM	CHEMBL4846416
8.96	EC50	1.1	nM	CHEMBL4848812
8.96	EC50	1.1	nM	CHEMBL4851368
8.96	EC50	1.1	nM	CHEMBL4855829
8.96	EC50	1.1	nM	CHEMBL4875443
8.96	EC50	1.1	nM	CHEMBL4853555
8.96	EC50	1.1	nM	CHEMBL4865653
8.96	EC50	1.1	nM	CHEMBL4863386
8.96	EC50	1.1	nM	CHEMBL4863198
8.96	EC50	1.1	nM	CHEMBL4866463
8.96	EC50	1.1	nM	CHEMBL4848606
8.96	EC50	1.1	nM	CHEMBL4858042
8.96	EC50	1.1	nM	CHEMBL4871052
8.96	EC50	1.1	nM	CHEMBL4863576
8.96	EC50	1.1	nM	CHEMBL4861950
8.96	EC50	1.1	nM	CHEMBL4847685
8.96	EC50	1.1	nM	CHEMBL4866193
8.96	EC50	1.1	nM	CHEMBL4876504
8.96	EC50	1.1	nM	CHEMBL4864049
8.96	EC50	1.1	nM	CHEMBL4877909
8.96	EC50	1.1	nM	CHEMBL4864476
8.96	EC50	1.1	nM	CHEMBL4867044
8.96	EC50	1.1	nM	CHEMBL4848379
8.96	EC50	1.1	nM	CHEMBL4855290
8.96	EC50	1.1	nM	CHEMBL4875102
8.96	EC50	1.1	nM	CHEMBL4863447
8.96	EC50	1.1	nM	CHEMBL4850812
8.96	EC50	1.1	nM	CHEMBL4846330
8.96	EC50	1.1	nM	CHEMBL4846775
8.96	EC50	1.1	nM	CHEMBL4876282
8.96	EC50	1.1	nM	CHEMBL4854218
8.96	EC50	1.1	nM	CHEMBL4849904
8.96	EC50	1.1	nM	CHEMBL4865996
8.96	EC50	1.1	nM	CHEMBL4852273
8.96	EC50	1.1	nM	CHEMBL4877494
8.96	EC50	1.1	nM	CHEMBL4878221
8.96	EC50	1.1	nM	CHEMBL4860064
8.96	EC50	1.1	nM	CHEMBL4852339
8.96	EC50	1.1	nM	CHEMBL4845846
8.96	EC50	1.1	nM	CHEMBL4877713
8.96	EC50	1.1	nM	CHEMBL4872112
8.96	EC50	1.1	nM	CHEMBL4868214

PubChem BioAssay actives

176 with measured affinity, of 345 total; 50 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
1-[2-[[3-(difluoromethyl)-5-fluorophenyl]methyl]-4-pyridinyl]-3-methyl-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0025	uM
1-[2-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-4-pyridinyl]-3-methyl-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0040	uM
N-(2-hydroxyethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0052	uM
1-[2-[[3-(difluoromethoxy)-5-fluorophenyl]methyl]-4-pyridinyl]-3-methyl-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0063	uM
N-(2-methoxyethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0096	uM
1-[5-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-3-pyridinyl]-3-methyl-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0100	uM
1-[4-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0100	uM
4-[2-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-4-methyl-1,3-thiazol-5-yl]-2-methylbenzamide	1452524: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0110	uM
1-[3-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]phenyl]-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0126	uM
2-cyclopropyl-N-(2-hydroxyethyl)-3-[[4-[[3-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]amino]benzamide	2077476: Agonist activity at GPR52 (unknown origin) transfected in HTLA cells co-transfected with tango plasmid assessed as beta-arrestin recrutiment incubated for 20 hrs by luminescence based microbeta2 microplate counter	ec50	0.0140	uM
N-(2-hydroxyethyl)-3,5-dimethyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0150	uM
3-[[4-[[2,4-bis(trifluoromethyl)phenyl]methyl]-2-pyridinyl]amino]-N-(2-hydroxyethyl)-2-methylbenzamide	2077476: Agonist activity at GPR52 (unknown origin) transfected in HTLA cells co-transfected with tango plasmid assessed as beta-arrestin recrutiment incubated for 20 hrs by luminescence based microbeta2 microplate counter	ec50	0.0170	uM
N-(2-methoxyethyl)-3,5-dimethyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0170	uM
1-[2-[[3-(difluoromethyl)-5-fluorophenyl]methyl]-4-pyridinyl]-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0199	uM
N-(2-hydroxyethyl)-5-(hydroxymethyl)-3-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0210	uM
N-(2-hydroxyethyl)-1-[4-[[3-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]-2,3-dihydroindole-4-carboxamide	2077476: Agonist activity at GPR52 (unknown origin) transfected in HTLA cells co-transfected with tango plasmid assessed as beta-arrestin recrutiment incubated for 20 hrs by luminescence based microbeta2 microplate counter	ec50	0.0220	uM
4-[3-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-1-methylpyrazol-5-yl]-2-methylbenzamide	1452524: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0230	uM
4-[2-[(3-chloro-5-fluorophenyl)methyl]-4-methyl-1,3-thiazol-5-yl]-2-methylbenzamide	1452524: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0250	uM
1-[4-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]-5-methyl-6,7-dihydropyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0251	uM
1-[4-[[3-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]-6,7-dihydro-5H-indazol-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0251	uM
1-[2-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-4-pyridinyl]-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0275	uM
N-(2-hydroxyethyl)-3-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzofuran-4-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0282	uM
3-[2-[(3-chloro-5-fluorophenyl)methyl]-1-benzothiophen-7-yl]-N-(2-methoxyethyl)benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0295	uM
N-(2-hydroxyethyl)-2-methyl-3-[[4-[[3-(trifluoromethoxy)phenyl]methyl]-2-pyridinyl]amino]benzamide	2077386: Agonist activity at wildtype human GPR52 transfected in HEK293 cells assessed as increase in cAMP level incubated for 15 mins by microbeta2 microplate counter based Glosensor assay	ec50	0.0300	uM
N-(2-hydroxyethyl)-3-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzofuran-7-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0347	uM
N-(2-hydroxyethyl)-3-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0372	uM
N-(2-hydroxyethyl)-3-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-4-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0380	uM
N-(2-hydroxyethyl)-3-[2-[[3-(trifluoromethyl)phenyl]methyl]indazol-4-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0389	uM
1-[2-[[4-chloro-3-fluoro-5-(trifluoromethyl)phenyl]methyl]-4-pyridinyl]-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0398	uM
N-(2-methoxyethyl)-3-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0427	uM
N-(2-hydroxyethyl)-1-methyl-3-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-5-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0450	uM
3-[[4-[(3-chloro-5-fluorophenyl)methyl]-2-pyridinyl]amino]-N-(2-hydroxyethyl)-2-methylbenzamide	2077386: Agonist activity at wildtype human GPR52 transfected in HEK293 cells assessed as increase in cAMP level incubated for 15 mins by microbeta2 microplate counter based Glosensor assay	ec50	0.0460	uM
N-(2-hydroxyethyl)-2-methyl-3-[[4-[[3-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]amino]benzamide	2077386: Agonist activity at wildtype human GPR52 transfected in HEK293 cells assessed as increase in cAMP level incubated for 15 mins by microbeta2 microplate counter based Glosensor assay	ec50	0.0470	uM
1-[2-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-4-pyridinyl]-5,6,7,8-tetrahydropyrazolo[4,5-c]azepin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0501	uM
N-(2-hydroxyethyl)-3-[[4-[(3-methoxyphenyl)methyl]-2-pyridinyl]amino]-2-methylbenzamide	2077386: Agonist activity at wildtype human GPR52 transfected in HEK293 cells assessed as increase in cAMP level incubated for 15 mins by microbeta2 microplate counter based Glosensor assay	ec50	0.0530	uM
N-(2-amino-2-oxoethyl)-3-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0549	uM
4-[4-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-2-methylimidazol-1-yl]-2-methylbenzamide	1452524: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0590	uM
N-(2-methoxyethyl)-5-methyl-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0620	uM
N-(2-methoxyethyl)-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0620	uM
1-[4-[[3-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]-6,7-dihydro-5H-pyrazolo[4,5-c]pyridin-4-one	1952862: Agonist activity at human GPR52 expressed in HEK293F assessed as cAMP accumulation preincubated for 30 mins followed by cAMP detection reagent and measured after 1 hr by HTRF analysis	ec50	0.0631	uM
N-(2-hydroxyethyl)-2-methoxy-3-[[4-[[3-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]amino]benzamide	2077386: Agonist activity at wildtype human GPR52 transfected in HEK293 cells assessed as increase in cAMP level incubated for 15 mins by microbeta2 microplate counter based Glosensor assay	ec50	0.0640	uM
N-(2-hydroxyethyl)-3-[2-[[3-(trifluoromethyl)phenyl]methyl]indazol-7-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0646	uM
2-methyl-4-[4-methyl-2-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-5-yl]benzamide	1452524: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0730	uM
4-[3-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-5-methyl-1,2,4-triazol-1-yl]-2-methylbenzamide	1452524: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0750	uM
N-(2-hydroxyethyl)-3-[3-methyl-2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzofuran-7-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0813	uM
2-ethyl-4-[4-methyl-2-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-5-yl]benzamide	1452524: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0830	uM
N-(2-amino-2-oxoethyl)-3-[4-fluoro-2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]benzamide	1224203: Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay	ec50	0.0832	uM
N-(2-hydroxyethyl)-2-thiophen-2-yl-3-[[4-[[3-(trifluoromethyl)phenyl]methyl]-2-pyridinyl]amino]benzamide	2077386: Agonist activity at wildtype human GPR52 transfected in HEK293 cells assessed as increase in cAMP level incubated for 15 mins by microbeta2 microplate counter based Glosensor assay	ec50	0.0840	uM
N-(2-hydroxyethyl)-1-[2-[[3-(trifluoromethyl)phenyl]methyl]-1-benzothiophen-7-yl]pyrazole-4-carboxamide	1389766: Agonist activity at human GPR52 expressed in CHO cells assessed as increase in cAMP level after 30 mins by AlphaScreen assay	ec50	0.0870	uM
N-(2-hydroxyethyl)-1-[6-[(3-methylphenyl)methyl]pyrimidin-4-yl]-2,3-dihydroindole-4-carboxamide	1700852: Agonist activity at human GPR52 expressed in HEK293 cells assessed as increase in cAMP levels incubated for 15 mins by Glosensor cAMP assay	ec50	0.0900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Hydrogen Peroxide	decreases expression	1
Ozone	affects expression, increases abundance	1
T-2 Toxin	decreases expression	1

ChEMBL screening assays

35 unique, capped per target: 27 functional, 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3367421	Binding	Agonist activity at GPR52 (unknown origin)	Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52. — J Med Chem
CHEMBL3367423	Functional	Agonist activity at human GPR52 expressed in CHO cells assessed as cAMP production after 30 mins by Alphascreen assay relative to N-(2-Hydroxyethyl)-3-{2-[3-(trifluoromethyl)benzyl]-1-benzofuran-4-yl}benzamide	Discovery of the first potent and orally available agonist of the orphan G-protein-coupled receptor 52. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX66	PathHunter CHO-K1 GPR52 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA44	PathHunter U2OS GPR52 beta-arrestin	Cancer cell line	Female

Clinical trials (associated diseases)

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