GPR35
Chr 2G protein-coupled receptor 35
The GPR35 protein is a G-protein coupled receptor that binds ligands including kynurenic acid, lysophosphatidic acid, and serotonin metabolites to regulate immune cell function, mitochondrial metabolism, and inflammatory responses. Mutations in GPR35 cause autosomal recessive primary immunodeficiency with recurrent infections and inflammatory bowel disease-like symptoms. The gene shows low constraint to loss-of-function variation (pLI 0.005, LOEUF 1.51), consistent with a recessive inheritance pattern where biallelic mutations are required for disease.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
GPR35 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools