GPR4 (G Protein-Coupled Receptor 4): Structure, Function, and Disease Relevance
A proton-sensing G protein-coupled receptor involved in pH homeostasis, inflammation, and cancer biology
Gene Information Card
| Symbol | GPR4 |
|---|---|
| Full Name | G protein-coupled receptor 4 |
| Gene Type | protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 2828 ncbi.nlm.nih.gov/gene/2828 |
| Ensembl ID | ENSG00000174473 |
| UniProt ID | P46093 |
| OMIM ID | 600849 |
| HGNC ID | 4479 |
| Aliases | GPR4, G-protein coupled receptor 4, GPR4 (proton-sensing) |
Description
GPR4 encodes a G protein-coupled receptor that functions as a proton sensor, responding to extracellular pH changes. It is involved in multiple physiological and pathological processes, including acid-base homeostasis, inflammation, and tumor biology. GPR4 is expressed in various tissues and cell types, and its dysregulation has been linked to several diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | GPR4 activation by acidic tumor microenvironment promotes cell proliferation, migration, and invasion through downstream signaling pathways (e.g., Gq/11, Rho, ERK). | Multiple studies in cell lines and animal models; COSMIC and PubMed indexed. |
| Inflammatory diseases (e.g., colitis, arthritis) | GPR4 mediates pro-inflammatory responses to acidosis, enhancing cytokine production and immune cell recruitment. | Preclinical models; PubMed indexed. |
| Vascular diseases (e.g., angiogenesis) | GPR4 regulates endothelial cell function and angiogenesis in response to pH changes. | In vitro and in vivo studies; PubMed indexed. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 15.2 | Medium |
| Kidney | 12.8 | Medium |
| Liver | 10.5 | Low |
| Brain | 8.3 | Low |
| Heart | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | High expression; used in functional studies |
| A549 | 14.2 | Lung cancer cell line; moderate expression |
| HUVEC | 12.0 | Endothelial cells; relevant for angiogenesis |
| MCF7 | 9.8 | Breast cancer cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.457C>T (p.Arg153Cys) | Missense | 0.01% (gnomAD) | Potential loss of function; affects ligand binding |
| c.100G>A (p.Gly34Ser) | Missense | 0.005% (gnomAD) | Unknown; may alter receptor activity |
| c.782A>G (p.Asn261Ser) | Missense | 0.002% (gnomAD) | Reported in COSMIC; possible gain-of-function in cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair proton sensing or downstream signaling, leading to reduced cellular responses to acidosis.
Gain of Function (GOF)
Mutations that enhance receptor activity, potentially promoting tumor progression or inflammation.
Dominant Negative (DN)
Not well characterized; some mutations may interfere with wild-type receptor function.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • proton binding |
| • signal transduction | • plasma membrane |
| • response to pH | • cell surface receptor signaling pathway |
Pathways
• GPCR downstream signaling
• Gq/11-mediated signaling
• Rho GTPase pathway
• ERK/MAPK pathway
• PI3K/Akt pathway
Protein Summary
GPR4 is a 7-transmembrane domain receptor that senses extracellular protons. Upon activation by low pH, it couples to G proteins (e.g., Gq/11) to initiate intracellular signaling cascades, modulating cell proliferation, migration, and cytokine release. It plays a role in pH homeostasis and is implicated in cancer and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPR4 Knockout HEK293 Cell Line | EDJ-KQ4761 | Human | 2828 | Details Get a Quote |
| GPR42 Knockout HEK293 Cell Line | EDJ-KQ4788 | Human | 2866 | Details Get a Quote |
| GPR45 Knockout HEK293 Cell Line | EDJ-KQ7350 | Human | 11250 | Details Get a Quote |
| GPR4 Knockout HeLa Cell Line | EDJ-KQ53383 | Human | 2828 | Details Get a Quote |
| GPR45 Knockout HeLa Cell Line | EDJ-KQ55611 | Human | 11250 | Details Get a Quote |
| GPR4 Knockout A-549 Cell Line | EDJ-KQ61861 | Human | 2828 | Details Get a Quote |
| GPR45 Knockout A-549 Cell Line | EDJ-KQ64110 | Human | 11250 | Details Get a Quote |
| GPR4 Knockout HCT 116 Cell Line | EDJ-KQ70343 | Human | 2828 | Details Get a Quote |
| GPR45 Knockout HCT 116 Cell Line | EDJ-KQ72555 | Human | 11250 | Details Get a Quote |
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