GPR37

Chr 7

G protein-coupled receptor 37

Also known as: EDNRBL, PAELR, hET(B)R-LP

NCBI Gene: 2861ENSG00000170775UniProt: O15354

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. [provided by RefSeq, Oct 2012]

111
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GPR37
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 75 VUS of 111 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.79LOEUF
pLI 0.000
Z-score 2.26
OE 0.45 (0.27–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.84Z-score
OE missense 0.88 (0.80–0.96)
316 obs / 360.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.27–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.80–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 9 / 19.9Missense obs/exp: 316 / 360.9Syn Z: 0.91

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS75
Likely Benign4
Benign6
24
Pathogenic
2
Likely Pathogenic
75
VUS
4
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
2
0
2
VUS
0
71
4
0
75
Likely Benign
0
3
0
1
4
Benign
0
1
0
5
6
Total075306111

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GPR37 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GPR37-enhanced ubiquitination of ATP1A1 inhibits tumor progression and radiation resistance in esophageal squamous cell carcinoma.
Hu J et al.·Cell Death Dis
2024
Role of orphan G-protein coupled receptors in tissue ischemia: A comprehensive review.
Keifi Bajestani A et al.·Eur J Pharmacol
2024Review
GPR37 expression as a prognostic marker in gliomas: a bioinformatics-based analysis.
Liang K et al.·Aging (Albany NY)
2023
Ecto-GPR37: a potential biomarker for Parkinson's disease.
Morató X et al.·Transl Neurodegener
2021
GPR37 promotes cancer growth by binding to CDK6 and represents a new theranostic target in lung adenocarcinoma.
Xie X et al.·Pharmacol Res
2022
Serum GPR37 as a novel biomarker for disease activity, disability, and differential diagnosis in NMOSD.
Li X et al.·Clin Chim Acta
2026
Emerging roles of the G-protein-coupled receptor 37 in neurological diseases and pain.
Wang X et al.·Neuroscience
2024Review
Functional GPR37 trafficking protects against toxicity induced by 6-OHDA, MPP+ or rotenone in a catecholaminergic cell line.
Lundius EG et al.·J Neurochem
2013Functional
Temporal biphasic regulation of photoreceptor degeneration by microglial TREM2: A metabolic-immune nexus in retinitis pigmentosa.
Li R et al.·Sci Adv
2025
The role of parkinson's disease-associated receptor GPR37 in the hippocampus: functional interplay with the adenosinergic system.
Lopes JP et al.·J Neurochem
2015Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Prognostic, chemotherapy and immunotherapy roles of GPR37/GPR37L1 in pan-cancer.
Zhu G et al.·Medicine (Baltimore)
2026🔓 Open Access
A bone-derived hormone permits rapid visual escape via GPR37 receptor in a subpopulation of VTA GABAergic neurons.
Liu X et al.·Neuron
2026
Bi-allelic loss-of-function variants in JKAMP cause a neurodevelopmental syndrome associated with dysregulation of GPR37 trafficking.
Chacon-Millan P et al.·Am J Hum Genet
2026
Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis.
Li Y et al.·J Clin Invest
2026🔓 Open Access
NPD1/GPR37 signaling protects against painful traumatic brain injury and comorbidities by regulating demyelination, glial responses, and neuroinflammation in the mouse brain.
Zhao J et al.·Brain Behav Immun
2026Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools