GPR88

Summary

GPR88 (G protein-coupled receptor 88, HGNC:4539) is a protein-coding gene on chromosome 1p21.2, encoding G protein-coupled receptor 88 (Q9GZN0). Orphan G protein-coupled receptor implicated in a large repertoire of behavioral responses that engage motor activities, spatial learning, and emotional processing.

The protein encoded by this gene is a G protein-coupled receptor found almost exclusively in the striatum, a brain structure that controls motor function and cognition. Defects in this gene have been associated with chorea, speech delay, and learning difficulties, as well as some neuropsychiatric disorders.

Source: NCBI Gene 54112 — RefSeq curated summary.

At a glance

• Gene–disease (curated): chorea, childhood-onset, with psychomotor retardation (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 103 total — 1 pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes
• MANE Select transcript: NM_022049

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4539
Approved symbol	GPR88
Name	G protein-coupled receptor 88
Location	1p21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000181656
Ensembl biotype	protein_coding
OMIM	607468
Entrez	54112

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000315033

RefSeq mRNA: 1 — MANE Select: NM_022049 NM_022049

CCDS: CCDS772

Canonical transcript exons

ENST00000315033 — 2 exons

Exon	Start	End
ENSE00001258674	100538139	100538502
ENSE00001451884	100538894	100542021

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 97.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.1251 / max 1108.7490, expressed in 134 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4237	2.8921	83
4241	0.7328	47
4243	0.4277	55
4236	0.1784	30
4240	0.1771	32
4235	0.1685	30
4242	0.1449	34
4239	0.1274	20
4238	0.1138	27
4247	0.0629	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	97.45	gold quality
putamen	UBERON:0001874	94.55	gold quality
caudate nucleus	UBERON:0001873	93.49	gold quality
nucleus accumbens	UBERON:0001882	90.62	gold quality
endothelial cell	CL:0000115	76.15	silver quality
entorhinal cortex	UBERON:0002728	73.22	gold quality
middle temporal gyrus	UBERON:0002771	71.86	silver quality
telencephalon	UBERON:0001893	71.61	gold quality
prefrontal cortex	UBERON:0000451	70.24	gold quality
right lobe of liver	UBERON:0001114	70.13	gold quality
forebrain	UBERON:0001890	68.45	gold quality
liver	UBERON:0002107	68.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.68	gold quality
Brodmann (1909) area 23	UBERON:0013554	67.44	gold quality
spleen	UBERON:0002106	67.31	gold quality
temporal lobe	UBERON:0001871	67.20	gold quality
anterior cingulate cortex	UBERON:0009835	66.15	gold quality
frontal cortex	UBERON:0001870	66.14	gold quality
cingulate cortex	UBERON:0003027	66.11	gold quality
neocortex	UBERON:0001950	65.94	gold quality
cerebral cortex	UBERON:0000956	65.15	gold quality
amygdala	UBERON:0001876	64.71	gold quality
superior frontal gyrus	UBERON:0002661	64.05	gold quality
primary visual cortex	UBERON:0002436	63.69	gold quality
cortical plate	UBERON:0005343	63.54	gold quality
brain	UBERON:0000955	63.28	gold quality
right frontal lobe	UBERON:0002810	62.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.22	gold quality
lower esophagus	UBERON:0013473	62.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting GPR88, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-30A-3P	99.87	69.74	2928

Literature-anchored findings (GeneRIF, showing 3)

• Study designed and synthesized a series of 2-PCCA analogues bearing a variety of substituents at the phenyl ring of the aniline moiety to determine the structure-activity relationship (SAR) in this region; SAR studies suggested that there is a hydrophobic pocket in the GPR88 binding site interacting with the aniline region of 2-PCCA (PMID:27499251)
• Activation and allosteric regulation of the orphan GPR88-Gi1 signaling complex. (PMID:35501348)
• The orphan receptor GPR88 controls impulsivity and is a risk factor for Attention-Deficit/Hyperactivity Disorder. (PMID:36075963)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gpr88	ENSMUSG00000068696
rattus_norvegicus	Gpr88	ENSRNOG00000026953

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), GPR83 (ENSG00000123901), MCHR1 (ENSG00000128285), OR11H1 (ENSG00000130538), MTNR1B (ENSG00000134640), MCHR2 (ENSG00000152034), NPY1R (ENSG00000164128), NPY5R (ENSG00000164129), MTNR1A (ENSG00000168412), PROKR1 (ENSG00000169618), TACR3 (ENSG00000169836), OR9G1 (ENSG00000174914), OR11H4 (ENSG00000176198), OR11H6 (ENSG00000176219), OR9A2 (ENSG00000179468), GPR19 (ENSG00000183150), NPY2R (ENSG00000185149), OR11G2 (ENSG00000196832), NPY4R (ENSG00000204174), OR11A1 (ENSG00000204694), OR9A1P (ENSG00000237621), OR11H12 (ENSG00000257115), OR9A4 (ENSG00000258083), OR11H2 (ENSG00000258453), OR11H7 (ENSG00000258806), NPY4R2 (ENSG00000264717), OR10X1 (ENSG00000279111), OR51F1 (ENSG00000280021)

Protein

Protein identifiers

G protein-coupled receptor 88 — Q9GZN0 (reviewed: Q9GZN0)

Alternative names: Striatum-specific G-protein coupled receptor

All UniProt accessions (1): Q9GZN0

UniProt curated annotations — full annotation on UniProt →

Function. Orphan G protein-coupled receptor implicated in a large repertoire of behavioral responses that engage motor activities, spatial learning, and emotional processing. May play a role in the regulation of cognitive and motor function. Couples with the heterotrimeric G protein complex of the G(i) subfamily, consisting of GNAI1, GNB1 and GNG2, thereby acting through a G(i)-mediated pathway. Plays a role in the attenuation of D1 dopamine receptor (D1R)-mediated cAMP response in ciliated cells. In non-ciliated cells, involved in the inhibition of the beta-2 adrenergic receptor (B2AR) response.

Subcellular location. Cell membrane. Cell projection. Cilium membrane. Cytoplasm. Nucleus.

Tissue specificity. Expressed predominantly in the striatum.

Disease relevance. Chorea, childhood-onset, with psychomotor retardation (COCPMR) [MIM:616939] An autosomal recessive neurodevelopmental disorder characterized by abnormal involuntary movements, marked speech delay, intellectual disability and learning difficulties. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_071332* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00001

UniProt features (40 total): mutagenesis site 10, helix 10, topological domain 8, transmembrane region 7, sequence variant 3, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7EJX	ELECTRON MICROSCOPY	2.4
7WZ4	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZN0-F1	76.73	0.41

Antibody-complex structures (SAbDab): 2 — 7EJX, 7WZ4

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): 3

Mutagenesis-validated functional residues (10):

Position	Phenotype
84	abolishes the responsiveness to synthetic agonist 2-pcca.
117	reduced g(i)-coupling activity.
121	reduced g(i)-coupling activity.
209	reduced g(i)-coupling activity.
216	reduced g(i)-coupling activity.
219	reduced g(i)-coupling activity.
283	inhibits d1r-dependent camp accumulation.
283	retains g(i)-protein-coupled signaling activity. abolishes the responsiveness to synthetic agonist 2-pcca.
287	reduced g(i)-coupling activity.
322	abolishes the responsiveness to synthetic agonist 2-pcca.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): AAGCAAT_MIR137, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_PHOTOTRANSDUCTION, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MODULE_205, GOBP_LEARNING, GOBP_ADRENERGIC_RECEPTOR_SIGNALING_PATHWAY, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, CAATGCA_MIR33, WTGAAAT_UNKNOWN

GO Biological Process (11): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), phototransduction (GO:0007602), locomotory behavior (GO:0007626), neuronal action potential (GO:0019228), neuromuscular process controlling balance (GO:0050885), motor learning (GO:0061743), cellular response to light stimulus (GO:0071482), signal transduction (GO:0007165), detection of visible light (GO:0009584), adrenergic receptor signaling pathway (GO:0071875)

GO Molecular Function (4): cytoskeletal motor activity (GO:0003774), beta2-adrenergic receptor activity (GO:0004941), G protein-coupled photoreceptor activity (GO:0008020), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cilium (GO:0005929), ciliary membrane (GO:0060170), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
cellular anatomical structure	3
G protein-coupled receptor activity	2
signal transduction	2
detection of light stimulus	2
adenylate cyclase activity	1
behavior	1
action potential	1
transmission of nerve impulse	1
musculoskeletal movement	1
neuromuscular process	1
learning	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
adrenergic receptor activity	1
molecular_function	1
beta-adrenergic receptor activity	1
detection of visible light	1
photoreceptor activity	1
transmembrane signaling receptor activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
cell projection membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR88	GPR6	P46095	760
GPR88	GPR52	Q9Y2T5	742
GPR88	GPR75	O95800	663
GPR88	GPR141	Q7Z602	648
GPR88	GPR63	Q9BZJ6	589
GPR88	GPR4	P46093	526
GPR88	GPR150	Q8NGU9	513
GPR88	GPR161	Q8N6U8	509
GPR88	ADORA2A	P29274	492
GPR88	PDE10A	Q9Y233	479
GPR88	SLC6A3	Q01959	478
GPR88	GPR26	Q8NDV2	475
GPR88	PPP1R1B	Q9UD71	473
GPR88	CARTPT	Q16568	464
GPR88	ARPP21	Q9UBL0	458

IntAct

7 interactions, top by confidence:

A	B	Type	Score
GNB1	GNAI1	psi-mi:“MI:0915”(physical association)	0.810
	GNB1	psi-mi:“MI:0915”(physical association)	0.560
GPR88	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): ATP13A3 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), SLC39A10 (Affinity Capture-MS), GRIN1 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), SLC5A3 (Affinity Capture-MS), MFSD8 (Affinity Capture-MS), ECSIT (Affinity Capture-MS), TMEM259 (Affinity Capture-MS), POTEF (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), MARCH6 (Affinity Capture-MS), SLC7A3 (Affinity Capture-MS), LGR4 (Affinity Capture-MS)

ESM2 similar proteins: O02662, O02666, O43603, O70432, O95665, P08588, P13945, P18090, P18825, P18871, P21917, P22086, P25100, P25962, P26255, P30729, P31387, P34971, P35365, P46626, P47899, P50406, P51436, P79148, P97714, Q01337, Q28524, Q28927, Q28998, Q5IS65, Q60474, Q60476, Q60483, Q6TLJ0, Q7TQN7, Q7TQP2, Q80UC6, Q8IZ08, Q91V45, Q924U1

Diamond homologs: E7F7V7, F1R332, O00254, O08858, O09047, O42604, O77408, P11616, P21450, P21451, P25101, P30975, P32745, P35359, P49146, P51476, P79113, P79798, P97266, P97295, Q16581, Q28468, Q28642, Q29010, Q29J90, Q4V622, Q58D85, Q5IS62, Q5KSU9, Q5REI5, Q61614, Q68J47, Q8BFQ3, Q8TCW9, Q90328, Q95L55, Q96G91, Q9EPB7, Q9ESP4, Q9ESQ4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	60
Likely benign	38
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
225846	NM_022049.3(GPR88):c.873C>A (p.Cys291Ter)	Pathogenic

SpliceAI

119 predictions. Top by Δscore:

Variant	Effect	Δscore
1:100538499:CAAGG:C	donor_loss	0.9800
1:100538500:AAG:A	donor_loss	0.9800
1:100538501:AGGT:A	donor_loss	0.9800
1:100538503:G:GA	donor_loss	0.9800
1:100538504:T:A	donor_loss	0.9800
1:100538443:G:GT	donor_gain	0.9700
1:100538893:GGCA:G	acceptor_gain	0.9600
1:100538889:GGCA:G	acceptor_loss	0.9500
1:100538892:A:AC	acceptor_loss	0.9500
1:100538893:G:C	acceptor_loss	0.9500
1:100538498:GCAAG:G	donor_gain	0.9400
1:100538888:T:A	acceptor_gain	0.9400
1:100538892:A:AG	acceptor_gain	0.9300
1:100538892:AG:A	acceptor_gain	0.9300
1:100538893:G:GG	acceptor_gain	0.9300
1:100538893:GG:G	acceptor_gain	0.9300
1:100538480:C:G	donor_gain	0.9100
1:100538893:GGC:G	acceptor_gain	0.9000
1:100538889:G:A	acceptor_gain	0.8900
1:100538479:GC:G	donor_gain	0.8300
1:100539005:C:A	acceptor_gain	0.8200
1:100538397:C:G	donor_gain	0.7800
1:100538897:GGACA:G	acceptor_gain	0.7800
1:100539003:ACC:A	acceptor_gain	0.7800
1:100538449:T:TG	donor_gain	0.7700
1:100538499:C:T	donor_gain	0.7700
1:100538503:G:GG	donor_gain	0.7500
1:100538880:T:A	acceptor_loss	0.7200
1:100538505:A:C	donor_loss	0.7000
1:100538300:C:G	donor_gain	0.6700

AlphaMissense

2367 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:100539172:T:C	F69S	0.999
1:100539175:T:A	I70N	0.999
1:100539182:C:A	N72K	0.999
1:100539182:C:G	N72K	0.999
1:100539220:T:G	M85R	0.999
1:100539994:T:C	F343S	0.999
1:100539994:T:G	F343C	0.999
1:100539099:G:C	G45R	0.998
1:100539151:T:C	L62P	0.998
1:100539167:C:A	N67K	0.998
1:100539167:C:G	N67K	0.998
1:100539171:T:C	F69L	0.998
1:100539173:C:A	F69L	0.998
1:100539173:C:G	F69L	0.998
1:100539175:T:G	I70S	0.998
1:100539196:A:T	D77V	0.998
1:100539199:T:C	L78P	0.998
1:100539201:A:C	S79R	0.998
1:100539203:C:A	S79R	0.998
1:100539203:C:G	S79R	0.998
1:100539207:T:C	C81R	0.998
1:100539208:G:A	C81Y	0.998
1:100539209:C:G	C81W	0.998
1:100539220:T:C	M85T	0.998
1:100539391:T:A	I142N	0.998
1:100539462:T:A	W166R	0.998
1:100539462:T:C	W166R	0.998
1:100539091:C:A	A42D	0.997
1:100539100:G:A	G45D	0.997
1:100539103:C:A	T46K	0.997

dbSNP variants (sampled 300 via entrez): RS1000719686 (1:100539203 C>A,T), RS1000962455 (1:100539779 G>T), RS1001214170 (1:100538768 C>T), RS1001514344 (1:100541544 A>C,G), RS1001975620 (1:100539289 C>T), RS1002248073 (1:100538476 C>A), RS1002726910 (1:100536288 C>A,T), RS1003254492 (1:100537052 AT>A), RS1003992194 (1:100540678 G>A), RS1005174032 (1:100536911 A>G), RS1005959191 (1:100542266 G>A), RS1006299918 (1:100542039 T>A), RS1006532413 (1:100539438 A>G), RS1006632075 (1:100538961 G>T), RS1006739694 (1:100542322 C>T)

Disease associations

OMIM: gene MIM:607468 | disease phenotypes: MIM:616939

GenCC curated gene-disease

Disease	Classification	Inheritance
chorea, childhood-onset, with psychomotor retardation	Limited	Autosomal recessive

Mondo (1): chorea, childhood-onset, with psychomotor retardation (MONDO:0014839)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0002072	Chorea
HP:0002457	Abnormal head movements
HP:0002465	Poor speech
HP:0004305	Involuntary movements

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90011770_31	Glaucoma (primary open-angle)	2.000000e-18

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3399910 (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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
RTI-122	Agonist	7.96	pEC50
RTI-13951-33	Agonist	7.6	pEC50
compound 2 [PMID: 24793972]	Full agonist	6.22	pEC50

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5183838	EC50	355 nM
CHEMBL5171511	EC50	501 nM

ChEMBL bioactivities

618 potent at pChembl≥5 of 622 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.24	EC50	0.57	nM	CHEMBL3400199
9.18	EC50	0.66	nM	CHEMBL3404056
9.17	EC50	0.68	nM	CHEMBL3400198
8.96	EC50	1.1	nM	CHEMBL3400197
8.92	EC50	1.2	nM	CHEMBL3404049
8.85	EC50	1.4	nM	CHEMBL3400200
8.85	EC50	1.4	nM	CHEMBL3404054
8.77	EC50	1.7	nM	CHEMBL3404055
8.74	EC50	1.8	nM	CHEMBL3404051
8.70	EC50	2	nM	CHEMBL3400204
8.70	EC50	2	nM	CHEMBL3404052
8.70	EC50	2	nM	CHEMBL5422227
8.60	EC50	2.5	nM	CHEMBL3400208
8.52	EC50	3	nM	CHEMBL3400203
8.52	EC50	3	nM	CHEMBL3401459
8.52	EC50	3	nM	CHEMBL3401460
8.52	EC50	3	nM	CHEMBL3401461
8.52	EC50	3	nM	CHEMBL3715838
8.52	EC50	3	nM	CHEMBL3719007
8.52	EC50	3	nM	CHEMBL3718084
8.52	EC50	3	nM	CHEMBL3714801
8.52	EC50	3	nM	CHEMBL3718807
8.52	EC50	3	nM	CHEMBL3716013
8.52	EC50	3	nM	CHEMBL3718515
8.52	EC50	3	nM	CHEMBL3715829
8.52	EC50	3	nM	CHEMBL3717562
8.52	EC50	3	nM	CHEMBL3715807
8.52	EC50	3	nM	CHEMBL3717656
8.52	EC50	3	nM	CHEMBL3716470
8.52	EC50	3	nM	CHEMBL3718875
8.52	EC50	3	nM	CHEMBL3718945
8.52	EC50	3	nM	CHEMBL3718796
8.51	EC50	3.1	nM	CHEMBL3401461
8.46	EC50	3.5	nM	CHEMBL3401460
8.33	EC50	4.7	nM	CHEMBL3400206
8.33	EC50	4.7	nM	CHEMBL3400196
8.29	EC50	5.1	nM	CHEMBL3400205
8.24	EC50	5.8	nM	CHEMBL3404053
8.18	EC50	6.6	nM	CHEMBL3400207
8.10	EC50	8	nM	CHEMBL3714828
8.00	EC50	10	nM	CHEMBL3400202
7.97	EC50	10.8	nM	CHEMBL5396804
7.96	EC50	11	nM	CHEMBL3400201
7.94	EC50	11.5	nM	CHEMBL5396804
7.86	EC50	13.8	nM	CHEMBL5175064
7.85	EC50	14	nM	CHEMBL5175064
7.82	EC50	15	nM	CHEMBL3401459
7.61	EC50	24.7	nM	CHEMBL5432580
7.60	EC50	25	nM	CHEMBL4452474
7.60	EC50	25.12	nM	CHEMBL4452474

PubChem BioAssay actives

464 with measured affinity, of 695 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
trans-(1R,2R)-N-[(1-aminocyclopentyl)methyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0006	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0007	uM
trans-(1R,2R)-N-[(2S)-2-amino-2-cyclohexylethyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0007	uM
trans-(1R,2R)-N-[(2S)-2-amino-3-methylbutyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0011	uM
N-[(2S)-2-amino-4-methylpentyl]-2-methyl-3-phenyl-N-(4-phenylphenyl)propanamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0012	uM
trans-(1R,2R)-N-(2-amino-2-methylpropyl)-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0014	uM
trans-(1R,2R)-N-[(2S,3R)-2-amino-3-methylpentyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0014	uM
trans-(1R,2R)-N-[(2S)-2-amino-3-cyclohexylpropyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0017	uM
trans-(1R,2R)-N-[(2R)-2-amino-4-methylpentyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0018	uM
trans-(1R,2R)-N-(3-amino-4-ethylhexyl)-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0020	uM
trans-(1R,2R)-N-[(2S)-4-methyl-2-(methylamino)pentyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0020	uM
4-[4-[[(2R,3R)-2-amino-3-methoxybutyl]-[(1R,2R)-2-pyridin-2-ylcyclopropanecarbonyl]amino]phenyl]benzoic acid	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0020	uM
trans-(1R,2R)-N-[2-(cyclopentylmethylamino)ethyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0025	uM
trans-(1R,2R)-N-[(3S)-3-amino-5-methylhexyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0030	uM
trans-(1R,2R)-N-[(2S,3S)-2-amino-3-methylpentyl]-N-[4-(4-propylphenyl)phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0031	uM
trans-(1R,2R)-N-[(2S,3S)-2-amino-3-methylpentyl]-N-[4-(4-propan-2-yloxyphenyl)phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0035	uM
trans-(1R,2R)-N-[(2S)-2-amino-2-phenylethyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0047	uM
trans-(1R,2R)-N-[2-(2-methylbutylamino)ethyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0047	uM
trans-(1R,2R)-N-[2-(3-methylbutylamino)ethyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0051	uM
trans-(1R,2R)-N-[(2S,3S)-2-acetamido-3-methylpentyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0058	uM
trans-(1R,2R)-N-[2-(cyclohexylmethylamino)ethyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0066	uM
trans-(1R,2R)-2-phenyl-N-(4-phenylphenyl)-N-(piperidin-3-ylmethyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0100	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-2-(5-fluoro-2-pyridinyl)-N-[4-(4-propan-2-yloxyphenyl)phenyl]cyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0108	uM
trans-(1R,2R)-N-[(2S)-2-amino-3,3-dimethylbutyl]-2-phenyl-N-(4-phenylphenyl)cyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0110	uM
N-methyl-1-[(2R)-2-[4-[(2S)-2-methylpentoxy]phenyl]-2-[[(2S)-2-phenylpropanoyl]amino]ethyl]triazole-4-carboxamide	1876404: Agonist activity at GPR88 (unknown origin) expressed in CHO cells coexpressing PPLS-HA assessed as reduction in forskolin-stimulated cAMP production and measured after 90 mins by Lance TR-FRET cAMP assay	ec50	0.0138	uM
trans-(1R,2R)-N-[(2S,3S)-2-amino-3-methylpentyl]-N-[4-[4-(methoxymethyl)phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0150	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-(4-propan-2-yloxyphenyl)phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0247	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-[4-(methoxymethyl)phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;dihydrochloride	1529633: Agonist activity at GPR88 (unknown origin) expressed in PPLS-HA-GPR88 CHO cells assessed as effect on forskolin-induced cAMP accumulation after 30 mins by Eu-cAMP tracer-based TR-FRET assay	ec50	0.0250	uM
trans-(1R,2R)-N-[2-(difluoromethoxy)ethyl]-N-[1,3-dimethyl-4-[6-[(2S)-1,1,1-trifluoropropan-2-yl]oxy-3-pyridinyl]indazol-7-yl]-2-pyrimidin-4-ylcyclopropane-1-carboxamide	2066553: Agonist activity at human GPR88 transfected in HEK293 cells incubated for 10 mins by Gi1 BRET assay	ec50	0.0260	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-(4-ethoxyphenyl)phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0263	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-[4-[(1S)-1-methoxyethyl]phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0278	uM
(2S)-N-[(1R)-2-(dimethylamino)-1-[4-(2-methylpentoxy)phenyl]ethyl]-2-phenylpropanamide	1192995: Agonist activity at GPR88 (unknown origin) transfected in forskolin-stimulated HEK cells assessed as inhibition of cAMP production after 30 mins by HTRF method relative to control	ec50	0.0290	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-[4-[(1R)-1-methoxyethyl]phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0291	uM
trans-(1R,2R)-N-[(2S,3S)-2-amino-3-methylpentyl]-N-[4-[4-(methoxymethyl)phenyl]phenyl]-2-phenylcyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0350	uM
trans-(1R,2R)-N-[2-(difluoromethoxy)ethyl]-N-[1-methyl-4-[6-[(2S)-1,1,1-trifluoropropan-2-yl]oxy-3-pyridinyl]indazol-7-yl]-2-pyrimidin-4-ylcyclopropane-1-carboxamide	2066553: Agonist activity at human GPR88 transfected in HEK293 cells incubated for 10 mins by Gi1 BRET assay	ec50	0.0360	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-[4-[(2R)-oxolan-2-yl]phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0361	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-2-(6-fluoro-2-pyridinyl)-N-[4-[4-(methoxymethyl)phenyl]phenyl]cyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0390	uM
1-[(2R)-2-[4-(cyclobutylmethoxy)phenyl]-2-[[(2S)-2-phenylpropanoyl]amino]ethyl]-N-methyltriazole-4-carboxamide	1876404: Agonist activity at GPR88 (unknown origin) expressed in CHO cells coexpressing PPLS-HA assessed as reduction in forskolin-stimulated cAMP production and measured after 90 mins by Lance TR-FRET cAMP assay	ec50	0.0398	uM
trans-(1R,2R)-N-[(2S,3S)-2-amino-3-methylpentyl]-N-[4-(4-ethylphenyl)phenyl]-2-phenylcyclopropane-1-carboxamide	1193743: Agonist activity at GPR88 (unknown origin) transfected into cells assessed as cAMP accumulation by HTRF assay	ec50	0.0440	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-[4-[(2S)-oxolan-2-yl]phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0444	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-[4-(methoxymethyl)phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide	1876404: Agonist activity at GPR88 (unknown origin) expressed in CHO cells coexpressing PPLS-HA assessed as reduction in forskolin-stimulated cAMP production and measured after 90 mins by Lance TR-FRET cAMP assay	ec50	0.0447	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-[4-(methoxymethyl)phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0450	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-(4-cyclopropyloxyphenyl)phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0451	uM
trans-(1R,2R)-N-[(2S)-2-amino-2-cyclobutylethyl]-N-[4-(4-propan-2-yloxyphenyl)phenyl]-2-pyrimidin-4-ylcyclopropane-1-carboxamide	2066553: Agonist activity at human GPR88 transfected in HEK293 cells incubated for 10 mins by Gi1 BRET assay	ec50	0.0470	uM
(2S)-N-[(1R)-2-[4-(hydroxymethyl)triazol-1-yl]-1-[4-[(2S)-2-methylpentoxy]phenyl]ethyl]-2-phenylpropanamide	1876404: Agonist activity at GPR88 (unknown origin) expressed in CHO cells coexpressing PPLS-HA assessed as reduction in forskolin-stimulated cAMP production and measured after 90 mins by Lance TR-FRET cAMP assay	ec50	0.0490	uM
trans-(1R,2R)-N-[2-(difluoromethoxy)ethyl]-N-[1-methyl-4-(4-propan-2-yloxyphenyl)indazol-7-yl]-2-pyrimidin-4-ylcyclopropane-1-carboxamide	2066553: Agonist activity at human GPR88 transfected in HEK293 cells incubated for 10 mins by Gi1 BRET assay	ec50	0.0520	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-2-(5-fluoro-2-pyridinyl)-N-[4-[4-(methoxymethyl)phenyl]phenyl]cyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0523	uM
trans-(1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-2-(6-fluoro-2-pyridinyl)-N-[4-(4-propan-2-yloxyphenyl)phenyl]cyclopropane-1-carboxamide;hydrochloride	2028197: Agonist activity at PPLS-HA tagged GPR88 (unknown origin) expressed in CHO cells assessed as cAMP accumulation incubated for 30 mins by TR-FRET Assay	ec50	0.0548	uM
(2S)-N-[(1S)-2-(5-amino-1,3,4-oxadiazol-2-yl)-1-[4-(2-methylpentoxy)phenyl]ethyl]-2-phenylpropanamide;hydrochloride	1701016: Agonist activity at GPR88 (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-induced cAMP production by TR-FRET assay	ec50	0.0589	uM
(2S)-N-[(1S)-2-(5-amino-1,3,4-oxadiazol-2-yl)-1-[4-(2-methylpentoxy)phenyl]ethyl]-2-phenylpropanamide	1876404: Agonist activity at GPR88 (unknown origin) expressed in CHO cells coexpressing PPLS-HA assessed as reduction in forskolin-stimulated cAMP production and measured after 90 mins by Lance TR-FRET cAMP assay	ec50	0.0590	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Chenodeoxycholic Acid	decreases expression, affects cotreatment	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1
Glycocholic Acid	affects cotreatment, decreases expression	1
Glycodeoxycholic Acid	affects cotreatment, decreases expression	1
Ifosfamide	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tartrazine	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

30 unique, capped per target: 23 functional, 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3405070	Functional	Agonist activity at GPR88 (unknown origin) transfected in forskolin-stimulated HEK cells assessed as inhibition of cAMP production after 30 mins by HTRF method relative to control	Design, synthesis, and evaluation of phenylglycinols and phenyl amines as agonists of GPR88. — Bioorg Med Chem Lett
CHEMBL4883474	Binding	PRESTO-Tango GPCRome screening (GPR88)	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_KX77	PathHunter CHO-K1 GPR88 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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