GPR35

Chr 2

G protein-coupled receptor 35

NCBI Gene: 2859 ENSG00000178623 UniProt: Q9HC97

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.

ResearchSummary from RefSeq, UniProt

Enables C-X-C chemokine receptor activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cardiac muscle cell apoptotic process; and response to ischemia. Acts upstream of or within chemokine-mediated signaling pathway. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.51

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.51LOEUF

pLI 0.005

Z-score 0.72

OE 0.68 (0.33–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.21Z-score

OE missense 0.96 (0.86–1.08)

213 obs / 221.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.33–1.51)

0≤0.351.4

Missense OE?0.96 (0.86–1.08)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 5.9Missense obs/exp: 213 / 221.6Syn Z: -0.40

Background carrier burden — how many people carry a rare variant somewhere in GPR35?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 74

430 rare PASS variants

Rare truncating (LoF)

1 in 2,300

57 rare PASS variants

Rare synonymous (reference)

1 in 130

232 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR35. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 90	1 in 3,000
South Asian	~43k	1 in 80	1 in 5,400
Remaining (unassigned)	~30k	1 in 80	1 in 3,300
European (Finnish)	~26k	1 in 220	1 in 950
Admixed American	~22k	1 in 72	1 in 800
African / African American	~21k	1 in 57	1 in 1,000
East Asian	~20k	1 in 160	≈ 1 in 6,100
Ashkenazi Jewish	~13k	1 in 260	1 in 480
Middle Eastern	~2,884	1 in 85	1 in 450

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓