GPR18

Chr 13

G protein-coupled receptor 18

Also known as: DRV2

NCBI Gene: 2841ENSG00000125245UniProt: Q14330

The GPR18 protein is a G protein-coupled receptor that regulates immune responses and inflammation resolution, particularly through endocannabinoid and resolvin D2 signaling pathways. Mutations in GPR18 cause neurodevelopmental disorders with immune dysfunction, following an autosomal recessive inheritance pattern. The gene shows very low constraint against loss-of-function variants (pLI near 0), suggesting tolerance to heterozygous loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
15
Pubs (1 yr)
91
P/LP submissions
0%
P/LP missense
1.80
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— GPR18
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
91 unique Pathogenic / Likely Pathogenic· 51 VUS of 146 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.80LOEUF
pLI 0.000
Z-score -0.60
OE 1.20 (0.78–1.80)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.42Z-score
OE missense 0.91 (0.81–1.04)
176 obs / 192.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.20 (0.78–1.80)
0≤0.351.4
Missense OE0.91 (0.81–1.04)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 13 / 10.9Missense obs/exp: 176 / 192.5Syn Z: -1.11
DN
0.6647th %ile
GOF
0.75top 25%
LOF
0.2971th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic89
Likely Pathogenic2
VUS51
Likely Benign4
89
Pathogenic
2
Likely Pathogenic
51
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
89
0
89
Likely Pathogenic
0
0
2
0
2
VUS
0
47
4
0
51
Likely Benign
0
3
0
1
4
Benign
0
0
0
0
0
Total050951146

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

View in ClinVar →

Protein Context — Lollipop Plot

GPR18 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
GPR18 Deletion in Mice Inversely Affects Vasoactive Signaling and Passive Biomechanical Properties of the Thoracic Aorta and Femoral Artery.
De Moudt S et al.·Int J Mol Sci
2026Open Access
Vascular Bed-Specific Endothelial Dysfunction and Age-Dependent Circadian Hypertension in Mice Lacking the Resolvin D2 Receptor GPR18.
de Moudt S et al.·FASEB J
2025Open Access
Resolvin D2/GPR18 signaling enhances monocytic myeloid-derived suppressor cell function to mitigate abdominal aortic aneurysm formation.
Bellotti P et al.·FASEB J
2024
Naringin dihydrochalcone alleviates sepsis-induced acute lung injury via improving gut microbial homeostasis and activating GPR18 receptor.
He S et al.·Int Immunopharmacol
2024
Potent, Selective Agonists for the Cannabinoid-like Orphan G Protein-Coupled Receptor GPR18: A Promising Drug Target for Cancer and Immunity.
Mahardhika AB et al.·J Med Chem
2024
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients