GPR35

protein-coding

G protein-coupled receptor 35, the group of G protein-coupled receptors, Class A orphans

Gene summary

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]

MANE transcript

NM_005301.5

Inheritance

—

ClinVar variants

U:59B:25

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr2:240,605,430-240,633,159

External References & Databases

Ensembl (ENSG00000178623)

Transcript & Mutation Effects

hg38 • Region Span ~27.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPR35 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 18

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005301.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				8 clinvar	3 clinvar	11
missense			59 clinvar	9 clinvar	5 clinvar	73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	59	17	8	84

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005301.5	RefSeq	NP_005292.2	1	MANE Select
ENST00000407714.2	Ensembl	ENSP00000384263.1	1	MANE Select
NM_001195381.3	RefSeq	NP_001182310.1	2	Standard
NM_001195382.3	RefSeq	NP_001182311.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuroactive ligand-receptor interaction - Homo sapiens (human)
GPCRs, Class A Rhodopsin-like
Signaling by GPCR
Signal Transduction
Class A/1 (Rhodopsin-like receptors)

Biological Process

cytoskeleton organization
G protein-coupled receptor signaling pathway
positive regulation of cytosolic calcium ion concentration
positive regulation of Rho protein signal transduction
positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway

Molecular Function

G protein-coupled receptor activity
C-X-C chemokine receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000438013
Coding exons: 2
Length: 25829
Individuals with no LoFs: 125305
Homozygous LoFs: 1
Heterozygous LoFs: 276
Defined: 125582
p: 0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.205	213	222	0.961	0.0000151	2147
Missense (PolyPhen)		51	63.914	0.79795		673
Synonymous	-0.397	113	108	1.05	0.00000775	771
Loss of Function	0.725	4	5.90	0.678	3.36e-7	58

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.0028	0.0027	notable
Ashkenazi Jewish	0.00090	0.00090	rare
East Asian	0	0.0	absent
Finnish	0.00017	0.00014	rare
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.000065	0.000065	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a receptor for kynurenic acid, an intermediate in the tryptophan metabolic pathway. The activity of this receptor is mediated by G-proteins that elicit calcium mobilization and inositol phosphate production through G(qi/o) proteins. {ECO:0000269|PubMed:16754668}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.550
RVIS EVS: 1.47
RVIS percentile EVS: 95.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.266

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium