GPR4

protein-coding

G protein-coupled receptor 4, the group of G protein-coupled receptors, Class A orphans

Gene summary

Enables G protein-coupled receptor activity. Involved in several processes, including G protein-coupled receptor signaling pathway; cellular response to acidic pH; and positive regulation of Rho protein signal transduction. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_005282.3

Inheritance

—

ClinVar variants

U:41B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr19:45,589,764-45,602,212

External References & Databases

Ensembl (ENSG00000177464)

Transcript & Mutation Effects

hg38 • Region Span ~12.4 kb

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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 GPR4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005282.3. 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						0
missense			41 clinvar	1 clinvar		42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	41	1	0	42

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005282.3	RefSeq	NP_005273.1	1	MANE Select
ENST00000323040.5	Ensembl	ENSP00000319744.3	1	MANE Select
ENST00000877384.1	Ensembl	ENSP00000547443.1	1	Standard
ENST00000877384.2	Ensembl	ENSP00000547443.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Class A Rhodopsin-like
Signaling by GPCR
Signal Transduction
Class A/1 (Rhodopsin-like receptors)
GPCR ligand binding

Biological Process

G protein-coupled receptor signaling pathway
response to acidic pH
negative regulation of angiogenesis
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

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000323040
Coding exons: 1
Length: 12445
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125732
p: 0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.53	138	251	0.550	0.0000166	2344
Missense (PolyPhen)		36	104.33	0.34507		1021
Synonymous	1.78	96	121	0.794	0.00000875	777
Loss of Function	1.85	3	9.00	0.333	3.86e-7	93

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000094	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Proton-sensing receptor coupled to several G-proteins, including G(s), G(13) and G(q)/G(11) proteins, leading to cAMP production. {ECO:0000269|PubMed:12955148, ECO:0000269|PubMed:17462861}.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.256
RVIS EVS: -0.41
RVIS percentile EVS: 26.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0664

Gene Damage Prediction

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