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): 104 total — 1 pathogenic
• GTEx eGene: eQTL in 18 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 7
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.77 (unconstrained)
• MANE Select transcript: NM_022049
• Notable: 104 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 2 — 2 protein_coding

MANE Select: ENST00000315033

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000315033, ENST00001145372

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.

Highest expression (Bgee): lateral globus pallidus, putamen, caudate nucleus, nucleus accumbens, endothelial cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GPR88 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Liver	eqtl	1.3e-20	-0.69	1:100575096:T:A
Adipose Subcutaneous	eqtl	3.0e-11	+0.31	1:100574454:C:T
Heart Atrial Appendage	eqtl	2.9e-08	+0.32	1:100574454:C:T
Artery Tibial	eqtl	3.8e-08	+0.52	1:100524531:C:CTA
Adipose Visceral Omentum	eqtl	4.2e-06	+0.28	1:100574454:C:T
Thyroid	eqtl	9.2e-06	+0.25	1:100583826:G:A
Breast Mammary Tissue	eqtl	5.5e-05	+0.24	1:100576886:ATCTG:A
Nerve Tibial	eqtl	3.5e-04	+0.19	1:100618717:C:T
Adrenal Gland	eqtl	7.3e-04	+0.38	1:100585653:C:T
Muscle Skeletal	eqtl	2.0e-03	+0.17	1:99898645:T:C
Heart Left Ventricle	eqtl	2.9e-03	+0.26	1:100586230:T:C
Brain Anterior cingulate cortex BA24	eqtl	5.5e-03	+0.59	1:99739491:G:T
Lung	eqtl	8.4e-03	-0.25	1:100706185:T:C
Esophagus Muscularis	eqtl	1.2e-02	+0.30	1:100527343:A:G
Colon Transverse	eqtl	1.4e-02	-0.35	1:100370196:C:T
Brain Nucleus accumbens basal ganglia	eqtl	2.2e-02	-0.39	1:100469141:A:T
Prostate	eqtl	4.3e-02	+1.05	1:100568955:C:T
Skin Sun Exposed Lower leg	eqtl	4.7e-02	-0.75	1:100578494:A:G

FANTOM5 promoters

showing 10 of 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

showing 100 of 266 tissues 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
ventricular zone	UBERON:0003053	61.99	gold quality
left ovary	UBERON:0002119	61.75	gold quality
mucosa of stomach	UBERON:0001199	61.55	gold quality
hypothalamus	UBERON:0001898	60.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	60.59	gold quality
cranial nerve II	UBERON:0000941	60.49	gold quality
postcentral gyrus	UBERON:0002581	59.97	silver quality
ganglionic eminence	UBERON:0004023	59.78	gold quality
nipple	UBERON:0002030	59.68	gold quality
Ammon’s horn	UBERON:0001954	58.92	gold quality
right ovary	UBERON:0002118	58.74	gold quality
right coronary artery	UBERON:0001625	58.66	gold quality
ovary	UBERON:0000992	57.85	gold quality
occipital lobe	UBERON:0002021	57.61	gold quality
parietal lobe	UBERON:0001872	57.32	silver quality
muscle layer of sigmoid colon	UBERON:0035805	57.18	gold quality
decidua	UBERON:0002450	56.55	gold quality
monocyte	CL:0000576	56.32	gold quality
leukocyte	CL:0000738	56.31	gold quality
mononuclear cell	CL:0000842	56.28	gold quality
globus pallidus	UBERON:0001875	55.68	gold quality
tibial artery	UBERON:0007610	55.38	gold quality
popliteal artery	UBERON:0002250	55.32	gold quality
embryo	UBERON:0000922	54.93	gold quality
colonic epithelium	UBERON:0000397	54.48	gold quality
choroid plexus epithelium	UBERON:0003911	54.08	silver quality
medulla oblongata	UBERON:0001896	54.06	silver quality
left coronary artery	UBERON:0001626	53.45	gold quality
coronary artery	UBERON:0001621	53.13	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
tibialis anterior	UBERON:0001385	51.83	silver quality
tibial nerve	UBERON:0001323	50.96	gold quality
granulocyte	CL:0000094	50.68	silver quality
deltoid	UBERON:0001476	50.57	gold quality
rectum	UBERON:0001052	50.46	gold quality
aorta	UBERON:0000947	50.43	gold quality
vermiform appendix	UBERON:0001154	50.00	gold quality
medial globus pallidus	UBERON:0002477	49.93	silver quality
CA1 field of hippocampus	UBERON:0003881	49.84	gold quality
apex of heart	UBERON:0002098	49.80	gold quality
quadriceps femoris	UBERON:0001377	49.51	gold quality
smooth muscle tissue	UBERON:0001135	49.47	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
lymph node	UBERON:0000029	48.97	silver quality
cerebellar vermis	UBERON:0004720	48.93	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
caecum	UBERON:0001153	48.84	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
epithelial cell of pancreas	CL:0000083	48.67	gold quality
substantia nigra	UBERON:0002038	48.62	gold quality
inferior olivary complex	UBERON:0002127	48.57	silver quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
colon	UBERON:0001155	48.36	gold quality
calcaneal tendon	UBERON:0003701	48.27	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
large intestine	UBERON:0000059	48.11	gold quality
thymus	UBERON:0002370	48.10	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
muscle tissue	UBERON:0002385	48.05	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
adenohypophysis	UBERON:0002196	47.89	gold quality
midbrain	UBERON:0001891	47.83	gold quality
anatomical system	UBERON:0000467	47.82	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
bone marrow cell	CL:0002092	47.75	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

HPA expression

RNA tissue specificity: Tissue enriched

60 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Caudate putamen	tissue	719.1
Putamen	tissue	358.6
Basal ganglia	tissue	232.9
Nucleus accumbens	tissue	85.8
Ventral forebrain	tissue	83.7
Frontal cortex	tissue	37.8
Septum	tissue	35.2
Spleen	tissue	9.9
Medulla oblongata	tissue	8.5
Liver	tissue	8.3
Breast	tissue	6.7
Olfactory bulb	tissue	2.8
Hippocampus	tissue	2.3
Hippocampal formation	tissue	2.3
Hypothalamus	tissue	2.1
Locus coeruleus	tissue	2.1
Amygdala	tissue	2.0
Midbrain	tissue	2.0
Postcentral gyrus	tissue	2.0
Superior colliculi	tissue	1.6
Cerebral cortex	tissue	1.4
Temporal cortex	tissue	1.4
Choroid plexus	tissue	1.3
Ovary	tissue	1.2
Occipital cortex	tissue	1.2
Pituitary gland	tissue	1.1
Pons	tissue	1.1
Prefrontal cortex	tissue	1.0
Parathyroid gland	tissue	1.0
Substantia nigra	tissue	0.9
Entorhinal cortex	tissue	0.9
Somatosensory cortex	tissue	0.9
Insular cortex	tissue	0.9
Spinal cord	tissue	0.8
Corpus callosum	tissue	0.8
Motor cortex	tissue	0.7
Retrosplenial and cingulate cortex	tissue	0.6
Periaqueductal gray	tissue	0.6
Retrosplenial cortex	tissue	0.6
Thalamus	tissue	0.5
Adipose tissue	tissue	0.4
Salivary gland	tissue	0.4
Retina	tissue	0.3
Rectum	tissue	0.3
Duodenum	tissue	0.3
Prostate	tissue	0.3
Adrenal gland	tissue	0.3
Heart muscle	tissue	0.2
Tongue	tissue	0.2
Cerebellum	tissue	0.2
Small intestine	tissue	0.2
Thymus	tissue	0.2
Appendix	tissue	0.2
Lymph node	tissue	0.1
Stomach 1	tissue	0.1
Esophagus	tissue	0.1
Smooth muscle	tissue	0.1
Colon	tissue	0.1
Lung	tissue	0.1
Kidney	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Caudate nucleus (146.5), Nucleus basalis of Meynert (116.4), Inferior olive (22.0), Centromedial thalamic nucleus (15.6), Claustrum (15.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GPR88 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 98 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 6.61e-08, LOEUF 1.77, missense Z -0.883 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000315033 — one region, missense o/e 0.78.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1927653) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 31 distinct phenotype terms.

Mouse phenotype (MP)	Records
hyperactivity	2
impaired coordination	2
increased exploration in new environment	2
abnormal motor learning	2
decreased anxiety-related response	1
circling	1
increased stereotypic behavior	1
decreased grooming behavior	1
abnormal nest building behavior	1
abnormal associative learning	1
abnormal nervous system electrophysiology	1
decreased vertical activity	1
abnormal excitatory postsynaptic currents	1
abnormal inhibitory postsynaptic currents	1
abnormal GABA-mediated receptor currents	1
abnormal neuron physiology	1
abnormal behavior	1
abnormal spatial working memory	1
impaired cued conditioning behavior	1
abnormal behavioral response to xenobiotic	1
decreased grip strength	1
increased serotonin level	1
increased excitatory postsynaptic current amplitude	1
abnormal habituation to a new environment	1
impaired active avoidance behavior	1

+6 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Drosophila pseudoobscura pseudoobscura	Q29J90	68.4%	Diamond
Drosophila melanogaster	Q9W534	68.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01349	ncRNA	100128787
CDC14A	protein-coding	8556
MIR553	ncRNA	693138
RTCA	protein-coding	8634

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 by resolution:

PDB	Title	Method	Resolution (Å)
7EJX	Structure of the GPR88-Gi1 signaling complex bound to a synthetic ligand	ELECTRON MICROSCOPY	2.4
7WZ4	Structure of an orphan GPCR-G protein signaling complex	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 7EJX, 7WZ4

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

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)

Type	Positions
N-linked (glcnac…) asparagine	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 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (8): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), phototransduction (GO:0007602), 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 (6): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cilium (GO:0005929), ciliary membrane (GO:0060170), membrane (GO:0016020)

GO top-level categories

30 GO namespaces:

Category	Terms
G protein-coupled receptor signaling pathway	3
G protein-coupled receptor activity	2
signal transduction	2
detection of light stimulus	2
cellular anatomical structure	2
adenylate cyclase activity	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled receptor signaling pathway	BP	direct assay
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	BP	direct assay
ciliary membrane	CC	direct assay
cilium	CC	direct assay
plasma membrane	CC	physical interaction
beta2-adrenergic receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 726 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR88	GPR6	P46095	686
GPR88	GPR52	Q9Y2T5	607
GPR88	GPR63	Q9BZJ6	601
GPR88	GPR139	Q6DWJ6	572
GPR88	GPR75	O95800	539
GPR88	GPR141	Q7Z602	529
GPR88	GNG7	O60262	520
GPR88	PDE10A	Q9Y233	509
GPR88	GPR83	Q9NYM4	507
GPR88	PPP1R1B	Q9UD71	478
GPR88	ADORA2A	P29274	476
GPR88	GPR150	Q8NGU9	468
GPR88	DPH5	Q9H2P9	465
GPR88	PDYN	P01213	460
GPR88	GPR161	Q8N6U8	458

IntAct

Human interaction partners of GPR88 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
POTEF	association	0.350	1

BioGRID (15 interactions; top human partners by supporting records): ATP12A (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), ECSIT (Affinity Capture-MS), GRIN1 (Affinity Capture-MS), LGR4 (Affinity Capture-MS), MARCH6 (Affinity Capture-MS), MFSD8 (Affinity Capture-MS), POTEF (Affinity Capture-MS), SLC39A10 (Affinity Capture-MS), SLC5A3 (Affinity Capture-MS), SLC7A3 (Affinity Capture-MS), TMEM259 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
GPR88	“up-regulates activity”	GNAI1	binding

Disease & clinical

Genetic variants

Variant evidence for GPR88: 104 ClinVar records (1 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	60
Likely benign	39
Benign	3

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
225846	NM_022049.3(GPR88):c.873C>A (p.Cys291Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore GPR88’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 60):

Position(s)	Effect	Δscore	Sites
1:100538503–100538504	donor_loss	0.9800	4
1:100538503	donor_loss	0.9700
1:100538504	donor_loss	0.9600
1:100538892–100538893	acceptor_loss	0.9500	6
1:100538888	acceptor_gain	0.9400
1:100538480	donor_gain	0.9100
1:100538889	acceptor_gain	0.8900
1:100539005	acceptor_gain	0.8200
1:100538397	donor_gain	0.7800
1:100538499	donor_gain	0.7700

AlphaMissense

852 missense substitutions predicted likely pathogenic (of 2,367 scored), across 230 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M85	9	0.938	0.999
D77	8	0.996	0.998
F69	8	0.984	0.999
F343	8	0.971	0.999
F293	8	0.964	0.994
N49	8	0.957	0.997
N332	8	0.957	0.996
N137	8	0.949	0.997
N67	8	0.945	0.998
H131	8	0.919	0.986
F231	8	0.913	0.990
W166	7	0.965	0.998
W84	7	0.957	0.997
N72	7	0.956	0.999
C81	7	0.950	0.998
C74	7	0.949	0.997
M161	7	0.944	0.973
E88	7	0.929	0.986
I142	7	0.923	0.998
I70	7	0.921	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
chorea, childhood-onset, with psychomotor retardation	Limited	Autosomal recessive	2

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

HPO phenotypes

7 phenotypes (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:

Study	Trait	p-value
GCST90011770_11	Glaucoma (primary open-angle)	2e-18

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3399910 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

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)

252 measured of 273 human assays (273 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3400199	EC50	0.57 nM
CHEMBL3404056	EC50	0.66 nM
CHEMBL3400198	EC50	0.68 nM
CHEMBL3400197	EC50	1.1 nM
CHEMBL3404049	EC50	1.2 nM
CHEMBL3400200	EC50	1.4 nM
CHEMBL3404054	EC50	1.4 nM
CHEMBL3404055	EC50	1.7 nM
CHEMBL3404051	EC50	1.8 nM
CHEMBL3400204	EC50	2 nM
CHEMBL3404052	EC50	2 nM
CHEMBL3400208	EC50	2.5 nM
CHEMBL3400203	EC50	3 nM
CHEMBL3401460	EC50	3.5 nM
CHEMBL3400206	EC50	4.7 nM
CHEMBL3400196	EC50	4.7 nM
CHEMBL3400205	EC50	5.1 nM
CHEMBL3404053	EC50	5.8 nM
CHEMBL3400207	EC50	6.6 nM
CHEMBL3400202	EC50	10 nM
CHEMBL3400201	EC50	11 nM
CHEMBL5396804	EC50	12 nM
CHEMBL5175064	EC50	14 nM
CHEMBL3401459	EC50	15 nM
CHEMBL3403781	EC50	29 nM
CHEMBL3400271	EC50	35 nM
CHEMBL5203114	EC50	40 nM
CHEMBL3400262	EC50	44 nM
CHEMBL4595209	EC50	45 nM
CHEMBL4784623	EC50	59 nM
CHEMBL4790638	EC50	59 nM
CHEMBL5184001	EC50	60 nM
CHEMBL3400263	EC50	61 nM
CHEMBL4583504	EC50	63 nM
CHEMBL3400274	EC50	66 nM
CHEMBL4751633	EC50	71 nM
CHEMBL3400266	EC50	72 nM
CHEMBL4760182	EC50	74 nM
CHEMBL5172064	EC50	74 nM
CHEMBL5172809	EC50	77 nM
CHEMBL4783876	EC50	78 nM
CHEMBL5189064	EC50	89 nM
CHEMBL3403782	EC50	90 nM
CHEMBL3400267	EC50	90 nM
CHEMBL3403783	EC50	91 nM
CHEMBL5171567	EC50	91 nM
CHEMBL5204827	EC50	91 nM
CHEMBL3400269	EC50	94 nM
CHEMBL5181466	EC50	95 nM
CHEMBL4456708	EC50	96 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	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	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	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tartrazine	decreases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GPR88 across ~30M SureChEMBL compounds — explore on Sugi Predict.