GPR37

Summary

GPR37 (G protein-coupled receptor 37, HGNC:4494) is a protein-coding gene on chromosome 7q31.33, encoding Prosaposin receptor GPR37 (O15354). G-protein-coupled receptor that plays a role in several physiological pathways such as resolution of inflammatory pain and oligodendrocyte differentiation.

This gene is a member of the G protein-coupled receptor family. The encoded protein contains seven transmembrane domains and is found in cell and endoplasmic reticulum membranes. G protein-coupled receptors are involved in translating outside signals into G protein mediated intracellular effects. This gene product interacts with Parkin and is involved in juvenile Parkinson disease.

Source: NCBI Gene 2861 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 92 total
• Druggable target: yes
• MANE Select transcript: NM_005302

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4494
Approved symbol	GPR37
Name	G protein-coupled receptor 37
Location	7q31.33
Locus type	gene with protein product
Status	Approved
Aliases	EDNRBL, hET(B)R-LP, PAELR
Ensembl gene	ENSG00000170775
Ensembl biotype	protein_coding
OMIM	602583
Entrez	2861

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000303921

RefSeq mRNA: 1 — MANE Select: NM_005302 NM_005302

CCDS: CCDS5792

Canonical transcript exons

ENST00000303921 — 2 exons

Exon	Start	End
ENSE00001166174	124743885	124747343
ENSE00001166181	124763954	124765792

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 99.67.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8366 / max 510.2450, expressed in 680 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86004	3.3990	508
86002	0.6314	118
86001	0.4502	79
86007	0.4357	104
86006	0.2852	115
86008	0.2640	155
86003	0.2060	72
86005	0.1299	64
86000	0.0354	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.67	gold quality
inferior vagus X ganglion	UBERON:0005363	99.35	gold quality
cranial nerve II	UBERON:0000941	99.30	gold quality
middle frontal gyrus	UBERON:0002702	98.89	gold quality
subthalamic nucleus	UBERON:0001906	98.32	gold quality
oocyte	CL:0000023	98.30	gold quality
medulla oblongata	UBERON:0001896	98.27	gold quality
ventral tegmental area	UBERON:0002691	98.26	gold quality
superior vestibular nucleus	UBERON:0007227	98.20	gold quality
lateral globus pallidus	UBERON:0002476	98.08	gold quality
inferior olivary complex	UBERON:0002127	97.87	gold quality
pons	UBERON:0000988	97.73	gold quality
corpus callosum	UBERON:0002336	97.72	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.55	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.50	gold quality
endothelial cell	CL:0000115	96.15	gold quality
postcentral gyrus	UBERON:0002581	95.78	gold quality
globus pallidus	UBERON:0001875	95.67	gold quality
parietal lobe	UBERON:0001872	95.62	gold quality
substantia nigra pars compacta	UBERON:0001965	95.41	gold quality
CA1 field of hippocampus	UBERON:0003881	95.39	gold quality
spinal cord	UBERON:0002240	95.35	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.99	gold quality
medial globus pallidus	UBERON:0002477	94.96	gold quality
frontal pole	UBERON:0002795	94.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.85	gold quality
entorhinal cortex	UBERON:0002728	93.07	gold quality
orbitofrontal cortex	UBERON:0004167	92.92	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.20	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1414.08
E-MTAB-9154	yes	421.07
E-MTAB-7316	yes	34.19
E-GEOD-84465	yes	10.77
E-CURD-10	no	249.52
E-ANND-3	no	3.08
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting GPR37, 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-3163	100.00	77.23	8605
HSA-MIR-98-3P	100.00	74.08	3907
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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6835-3P	99.93	70.49	2904
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

Literature-anchored findings (GeneRIF, showing 19)

• results show that panneuronal expression of Parkin substrate Pael-R causes age-dependent selective degeneration of Drosophila dopaminergic (DA) neurons; coexpression of Parkin degrades Pael-R and suppresses its toxicity (PMID:12670421)
• Glup/PACRG suppresses cell death induced by accumulation of unfolded Pael receptor and facilitates the formation of Pael-R inclusions. (PMID:14532270)
• These results suggest that 4-PBA suppresses ER stress by directly reducing the amount of misfolded protein, including Pael-R accumulated in the ER. (PMID:16539653)
• Parkin-ko/Pael-R-tg mice represents an AR-JP mouse model displaying chronic and selective loss of catecholaminergic neurons. (PMID:18691389)
• Data show that GPR37 overexpression can induce cellular autophagy, which may prevent the selective degeneration of GPR37-expressing neurons, as reported for Parkinson’s and related neurodegenerative diseases. (PMID:19218498)
• GPR37 surface trafficking in heterologous cells can be greatly enhanced by N-terminal truncation, coexpression with other receptors, and coexpression with syntenin-1. (PMID:19799451)
• results suggested that some alleles in GPR37 were related to the deleterious effect of ASD. GPR37 is associated with the dopamine transporter to modulate dopamine uptake, and regulates behavioral responses to dopaminergic drugs (PMID:23251443)
• GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin. (PMID:23690594)
• Positive role of GPR37 in the proliferation of multiple myeloma cells. (PMID:24290813)
• GPR37 may play an important role in the pathogenesis of hepatocellular carcinoma by affecting the proliferation of HCC cells. (PMID:25169131)
• GPR37 was shown to be a component of the CASPR2-MUPP1 complex in brain. (PMID:25977097)
• REG4 promotes peritoneal metastasis of gastric cancer through GPR37 and triggers a positive feedback loop. (PMID:27036049)
• Study supports the idea that protein levels of parkin associated endothelin like receptor are likely regulated by a multitude of proteins including parkin, protein kinase C interacting protein and gamma-aminobutyrate type A receptor associated protein like 2 via mechanisms that include ubiquitination, proteasomal degradagtion and autophagy. (PMID:29496607)
• Up-regulation of GPR37 promotes the proliferation of human glioma U251 cells (PMID:29973325)
• An interaction between GPR37 and both splice forms of D2R was detected. (PMID:30423289)
• Ecto-GPR37: a potential biomarker for Parkinson’s disease. (PMID:33637132)
• GPR37 promotes cancer growth by binding to CDK6 and represents a new theranostic target in lung adenocarcinoma. (PMID:35934193)
• Activation of PI3K/Akt pathway by G protein-coupled receptor 37 promotes resistance to cisplatin-induced apoptosis in non-small cell lung cancer. (PMID:37732632)
• GPR37 promotes colorectal cancer liver metastases by enhancing the glycolysis and histone lactylation via Hippo pathway. (PMID:37749229)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr37b	ENSDARG00000033296
danio_rerio	gpr37a	ENSDARG00000074563
mus_musculus	Gpr37	ENSMUSG00000039904
rattus_norvegicus	Gpr37	ENSRNOG00000002524
caenorhabditis_elegans		WBGENE00019224

Paralogs (15): NTSR1 (ENSG00000101188), BRS3 (ENSG00000102239), MLNR (ENSG00000102539), GHSR (ENSG00000121853), GRPR (ENSG00000126010), NMUR2 (ENSG00000132911), NMBR (ENSG00000135577), EDNRB (ENSG00000136160), EDNRA (ENSG00000151617), NTSR2 (ENSG00000169006), GPR37L1 (ENSG00000170075), NMUR1 (ENSG00000171596), GPR148 (ENSG00000173302), TRHR (ENSG00000174417), GPR39 (ENSG00000183840)

Protein

Protein identifiers

Prosaposin receptor GPR37 — O15354 (reviewed: O15354)

Alternative names: Endothelin B receptor-like protein 1, G-protein coupled receptor 37, Parkin-associated endothelin receptor-like receptor

All UniProt accessions (1): O15354

UniProt curated annotations — full annotation on UniProt →

Function. G-protein-coupled receptor that plays a role in several physiological pathways such as resolution of inflammatory pain and oligodendrocyte differentiation. Acts as a receptor for several ligands including prosaposin, osteocalcin or neuroprotectin D1. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade. Acts as a receptor for osteocalcin (OCN) to regulate oligodendrocyte differentiation and central nervous system myelination. Mechanistically, plays a negative role in oligodendrocyte differentiation and myelination during development via activation of the ERK1/2 signaling pathway. Therefore, regulates the stability of myelin or resistance of myelin itself to demyelination. Upon activation by neuroprotectin D1 (NPD1), promotes the activation of phagocytosis in macrophages as well as the shift in cytokine release toward an anti-inflammatory profile, and thus helps to reverse inflammatory pain. In addition, the increased macrophage phagocytosis mediates protection against sepsis upon pathogen infection. Additionally, extracellular vesicles derived from efferocyte express prosaposin, which binds to macrophage GPR37 to increase expression of the efferocytosis receptor TIM4 via an ERK-AP1-dependent signaling axis, leading to increased macrophage efferocytosis efficiency and accelerated resolution of inflammation. May also act as a maturation factor of LRP6, protecting LRP6 from the endoplasmic reticulum (ER)-associated protein degradation (ERAD) and thereby promoting the Wnt/beta-catenin signaling pathway.

Subunit / interactions. Forms a complex with PRKN, STUB1 and HSP70. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PRKN, thus facilitating PRKN-mediated GPR37 ubiquitination. Interacts with PACRG. Interacts with MPDZ. Interacts with CNTNAP2. Interacts with LRP6; this interaction promotes LRP6 maturation.

Subcellular location. Cell projection. Dendrite. Synapse. Cell membrane. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in brain and spinal cord, and at lower levels in testis, placenta and liver, but no detectable expression observed in any other tissue. When overexpressed in cells, tends to become insoluble and unfolded. Accumulation of the unfolded protein may lead to dopaminergic neuronal death in juvenile Parkinson disease (PDJ).

Post-translational modifications. The N-terminus is cleaved by ADAM10 metalloproteinase; mediating limited proteolysis leading to the release of receptor ectodomain by shedding. In addition, cleaved by FURIN between Arg-54 and Asp-55. Ubiquitinated by PRKN in the presence of UBE2E1 and UBE2L3 in the endoplasmic reticulum. The unfolded form is specifically ubiquitinated by SYVN1, which promotes its proteasomal degradation and prevents neuronal cell death.

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

RefSeq proteins (1): NP_005293* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR003909	GPR37_orph	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (40 total): sequence conflict 11, topological domain 8, transmembrane region 7, glycosylation site 3, region of interest 2, compositionally biased region 2, site 2, mutagenesis site 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15354-F1	62.33	0.18

Functional residue map

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

Catalytic / active sites (2): 54–55 (cleavage; by furin); 167–168 (cleavage)

Disulfide bonds (1): 334–419

Glycosylation sites (3): 36, 222, 239

Mutagenesis-validated functional residues (2):

Position	Phenotype
54	strong increase of full-length receptor abundance at the cell surface.
558	strong loss of interaction with mupp1 resulting in dendritic alteration.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 210 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_DENDRITE_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_BEHAVIOR, PEREZ_TP63_TARGETS, GOBP_POSITIVE_REGULATION_OF_AMINE_METABOLIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP

GO Biological Process (10): G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), neuropeptide signaling pathway (GO:0007218), dendrite development (GO:0016358), locomotion involved in locomotory behavior (GO:0031987), cellular response to reactive oxygen species (GO:0034614), dopamine biosynthetic process (GO:0042416), positive regulation of MAPK cascade (GO:0043410), positive regulation of dopamine metabolic process (GO:0045964), signal transduction (GO:0007165)

GO Molecular Function (11): G protein-coupled receptor activity (GO:0004930), neuropeptide receptor activity (GO:0008188), G protein-coupled peptide receptor activity (GO:0008528), PDZ domain binding (GO:0030165), Hsp70 protein binding (GO:0030544), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), prosaposin receptor activity (GO:0036505), peptide binding (GO:0042277), neuropeptide binding (GO:0042923), protein binding (GO:0005515)

GO Cellular Component (11): ubiquitin ligase complex (GO:0000151), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cell surface (GO:0009986), dendrite (GO:0030425), signaling receptor complex (GO:0043235), synapse (GO:0045202), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
G protein-coupled receptor activity	3
G protein-coupled receptor signaling pathway	2
dopamine metabolic process	2
binding	2
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
neuron projection development	1
anatomical structure development	1
locomotory behavior	1
locomotion	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
catecholamine biosynthetic process	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
positive regulation of amine metabolic process	1
regulation of dopamine metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
peptide receptor activity	1
protein domain specific binding	1
heat shock protein binding	1
protein-folding chaperone binding	1
protein binding	1
ubiquitin-like protein ligase binding	1
peptide binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1389 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR37	PSAP	P07292	969
GPR37	PRKN	O60260	862
GPR37	SNCAIP	Q9Y6H5	797
GPR37	SNCA	P37840	781
GPR37	SLC6A3	Q01959	707
GPR37	STUB1	Q9UNE7	693
GPR37	SEPTIN5	Q99719	663
GPR37	BAG5	Q9UL15	644
GPR37	SYT11	Q9BT88	637
GPR37	REG4	Q9BYZ8	629
GPR37	AIMP2	Q13155	626
GPR37	GPR32	O75388	603
GPR37	CMKLR2	P46091	584
GPR37	CMKLR1	Q99788	566
GPR37	HSPA4	P34932	555

IntAct

120 interactions, top by confidence:

A	B	Type	Score
GPR37	SLC3A2	psi-mi:“MI:0915”(physical association)	0.580
GPR37	HTR4	psi-mi:“MI:0915”(physical association)	0.580
GPR37	HTR4	psi-mi:“MI:2364”(proximity)	0.580
GPR37	HTR4	psi-mi:“MI:0403”(colocalization)	0.580
GPR37	ADORA2A	psi-mi:“MI:0915”(physical association)	0.580
SLC3A2	GPR37	psi-mi:“MI:0915”(physical association)	0.580
GPR37	FABP7	psi-mi:“MI:0915”(physical association)	0.560
GPR37	PXN	psi-mi:“MI:0915”(physical association)	0.560
GPR37	SDC2	psi-mi:“MI:0915”(physical association)	0.560
GPR37	YY1	psi-mi:“MI:0915”(physical association)	0.560
GPR37	APLN	psi-mi:“MI:0915”(physical association)	0.560
GPR37	CREB5	psi-mi:“MI:0915”(physical association)	0.560
GPR37	PUM1	psi-mi:“MI:0915”(physical association)	0.560
GPR37	NR1D2	psi-mi:“MI:0915”(physical association)	0.560
GPR37	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
GPR37	ZFHX2	psi-mi:“MI:0915”(physical association)	0.560
GPR37	SCAMP4	psi-mi:“MI:0915”(physical association)	0.560
GPR37	SPATA3	psi-mi:“MI:0915”(physical association)	0.560
GPR37	FAM76B	psi-mi:“MI:0915”(physical association)	0.560
GPR37	MSRB3	psi-mi:“MI:0915”(physical association)	0.560
GPR37	LCE2A	psi-mi:“MI:0915”(physical association)	0.560
GPR37		psi-mi:“MI:0915”(physical association)	0.560

BioGRID (117): NXF1 (Affinity Capture-MS), FAM219A (Affinity Capture-MS), PTPRD (Affinity Capture-MS), WDFY1 (Affinity Capture-MS), ABCB8 (Affinity Capture-MS), ATE1 (Affinity Capture-MS), PPP2R5D (Affinity Capture-MS), POLD2 (Affinity Capture-MS), MBOAT7 (Affinity Capture-MS), GPR37 (Affinity Capture-MS), GPR37 (Affinity Capture-RNA), GABARAPL2 (Two-hybrid), GABARAPL2 (Reconstituted Complex), Mpdz (Reconstituted Complex), GPR37 (Affinity Capture-MS)

ESM2 similar proteins: A4IFJ1, A6NMD0, O15354, O60883, O76081, P07700, P11615, P13207, P14138, P15692, P35368, P48299, P79348, Q00731, Q14439, Q15583, Q17QD8, Q3UVY1, Q4R6Y5, Q5M871, Q5NRP8, Q64017, Q68CR7, Q6P050, Q6UYE1, Q76NI1, Q7TSN5, Q7TSN6, Q80WT4, Q86SP6, Q8K3V5, Q8K4Z2, Q8N5Z5, Q8NAU1, Q8R0N9, Q8TDV0, Q8TDX9, Q8WTX9, Q8WWF5, Q924Y8

Diamond homologs: O15354, O60883, P14600, P25103, P30547, P30548, P49146, P79113, P97295, Q15761, Q17QD8, Q28468, Q5DUB1, Q5DUB3, Q5IS62, Q95M54, Q969F8, Q99JG2, Q9DDN6, Q9EP86, Q9GK74, Q9GZQ6, Q9MYW9, Q9QY42, Q9QYC5, Q9QYC6, Q9Z2D5, O15218, O43613, O62709, O97661, Q0GBZ5, Q8NFJ6, Q8R416, Q8SPN2, Q8TCW9, Q923X5, Q9JKL1, A0A287A2K5, C3ZQF9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
GPR37	up-regulates	“ER stress”
PRKN	“down-regulates quantity by destabilization”	GPR37	ubiquitination
SYVN1	“down-regulates quantity by destabilization”	GPR37	polyubiquitination
SYVN1	“down-regulates quantity by destabilization”	GPR37	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Class A/1 (Rhodopsin-like receptors)	7	12.4×	1e-04
G alpha (s) signalling events	7	12.2×	1e-04
GPCR ligand binding	7	10.7×	2e-04
GPCR downstream signalling	7	7.2×	1e-03
Signaling by GPCR	7	6.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
calcium ion transport	5	14.6×	4e-03
locomotory behavior	5	14.5×	4e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	6	10.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

493 predictions. Top by Δscore:

Variant	Effect	Δscore
7:124747343:CCTG:C	acceptor_loss	0.9900
7:124747344:C:CA	acceptor_loss	0.9900
7:124747345:T:A	acceptor_loss	0.9900
7:124747340:CGAC:C	acceptor_gain	0.9800
7:124762602:C:CT	donor_gain	0.9800
7:124762603:T:TT	donor_gain	0.9800
7:124763948:CATTA:C	donor_loss	0.9700
7:124763949:ATTAC:A	donor_loss	0.9700
7:124763950:TTACC:T	donor_loss	0.9700
7:124763951:TACCT:T	donor_loss	0.9700
7:124763952:ACCT:A	donor_loss	0.9700
7:124763953:C:CG	donor_loss	0.9700
7:124763953:CCT:C	donor_gain	0.9700
7:124764001:T:TA	donor_gain	0.9600
7:124746706:T:TC	acceptor_gain	0.9500
7:124747344:C:CC	acceptor_gain	0.9500
7:124746706:T:C	acceptor_gain	0.9300
7:124762246:T:A	donor_gain	0.9100
7:124763952:A:AC	donor_gain	0.9100
7:124763953:C:CC	donor_gain	0.9100
7:124763947:GCATT:G	donor_loss	0.8900
7:124747339:GCGAC:G	acceptor_gain	0.8700
7:124747340:CGACC:C	acceptor_gain	0.8700
7:124763954:C:G	donor_loss	0.8700
7:124747747:G:T	donor_gain	0.8600
7:124757840:A:AC	donor_gain	0.8300
7:124747341:GAC:G	acceptor_gain	0.8200
7:124748146:C:CA	acceptor_gain	0.8200
7:124765500:C:CA	donor_gain	0.8100
7:124747355:C:CT	acceptor_loss	0.8000

AlphaMissense

3951 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:124746847:G:T	P507H	1.000
7:124746862:C:T	G502E	1.000
7:124747006:G:C	P454R	1.000
7:124747006:G:T	P454H	1.000
7:124747210:A:T	I386K	1.000
7:124747303:A:G	L355P	1.000
7:124746730:G:C	P546R	0.999
7:124746730:G:T	P546Q	0.999
7:124746847:G:C	P507R	0.999
7:124746857:A:G	C504R	0.999
7:124746863:C:G	G502R	0.999
7:124746863:C:T	G502R	0.999
7:124746877:A:G	L497P	0.999
7:124746986:A:G	C461R	0.999
7:124747007:G:A	P454S	0.999
7:124747013:A:G	C452R	0.999
7:124747022:A:G	C449R	0.999
7:124747024:C:T	G448D	0.999
7:124747034:A:G	W445R	0.999
7:124747034:A:T	W445R	0.999
7:124747037:A:G	W444R	0.999
7:124747037:A:T	W444R	0.999
7:124747202:C:G	G389R	0.999
7:124747202:C:T	G389R	0.999
7:124747208:A:G	W387R	0.999
7:124747208:A:T	W387R	0.999
7:124747210:A:C	I386R	0.999
7:124747291:C:G	R359P	0.999
7:124747292:G:T	R359S	0.999
7:124747294:T:A	D358V	0.999

dbSNP variants (sampled 300 via entrez): RS1000016522 (7:124755099 G>A,C), RS1000095991 (7:124756366 A>G), RS1000205915 (7:124757754 T>C,G), RS1000239050 (7:124747578 G>A), RS1000557533 (7:124754832 G>C), RS1000792802 (7:124760285 T>C), RS1001056965 (7:124750506 C>T), RS1001246315 (7:124745898 A>C), RS1001348592 (7:124766709 C>A,G), RS1001388567 (7:124748930 G>A), RS1001425404 (7:124753725 C>A,T), RS1001618138 (7:124761545 C>T), RS1001734124 (7:124762015 A>C), RS1001802986 (7:124758722 C>T), RS1001821128 (7:124754153 T>C)

Disease associations

OMIM: gene MIM:602583 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002062_7	Reading and spelling	8.000000e-06
GCST003061_10	Cutaneous malignant melanoma	5.000000e-07
GCST005529_11	Ankylosing spondylitis	5.000000e-07
GCST005529_68	Ankylosing spondylitis	2.000000e-06
GCST010002_262	Refractive error	4.000000e-08
GCST010303_24	Nevus count or cutaneous melanoma	2.000000e-15
GCST010304_58	Cutaneous malignant melanoma	2.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005301	reading and spelling ability
EFO:0004632	nevus count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523862 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Class A Orphans with emerging pharmacology

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
neuropeptide head activator	Agonist	8.48	pEC50
prosaptide	Agonist	8.15	pEC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	9
trichostatin A	affects cotreatment, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
methylselenic acid	increases expression	1
VX-agent	increases expression	1
arsenite	decreases methylation	1
sodium arsenite	affects methylation	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
tobacco tar	decreases expression	1
pentanal	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Carmustine	decreases expression	1
Cycloheximide	decreases reaction, increases expression	1
Doxorubicin	affects expression	1
Estradiol	decreases expression	1
Etoposide	affects response to substance	1
Folic Acid	decreases expression	1
Ozone	increases abundance, increases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883449	Binding	PRESTO-Tango GPCRome screening (GPR37)	Data for DCP probe UCSF924
CHEMBL5665250	Functional	Agonist activity at GPR37 receptor (unknown origin)	In silico design of novel probes for the atypical opioid receptor MRGPRX2. — Nat Chem Biol

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX60	PathHunter CHO-K1 GPR37 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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