GPR68: Proton-Sensing G Protein-Coupled Receptor in pH Homeostasis and Cancer
Comprehensive gene card for GPR68 (OGR1), a proton-sensing GPCR involved in tumor microenvironment, inflammation, and bone physiology.
Gene Information Card
| Symbol | GPR68 |
|---|---|
| Full Name | G protein-coupled receptor 68 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q31.3 |
| NCBI Gene ID | 8111 ncbi.nlm.nih.gov/gene/8111 |
| Ensembl ID | ENSG00000119714 |
| UniProt ID | Q15743 |
| OMIM ID | 601404 |
| HGNC ID | 4519 |
| Aliases | OGR1, GPR12A |
Description
GPR68 (OGR1) encodes a proton-sensing G protein-coupled receptor that is activated by extracellular acidification. It couples to Gq/11 and Gs proteins, leading to inositol phosphate production and cAMP accumulation. GPR68 plays key roles in pH homeostasis, bone resorption, inflammation, and cancer progression, particularly in the acidic tumor microenvironment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Acidic tumor microenvironment activates GPR68, promoting cell proliferation, migration, and invasion via Gq/11 signaling. | PMID: 25977310, 28753428 |
| Osteoporosis | GPR68 mediates osteoclast differentiation and bone resorption in response to local acidosis. | PMID: 16990588 |
| Inflammatory bowel disease | GPR68 expression is upregulated in inflamed colonic epithelium; receptor activation modulates barrier function and immune responses. | PMID: 29262323 |
| Ischemic stroke | GPR68 is expressed in brain microvascular endothelial cells and contributes to blood-brain barrier disruption under acidosis. | PMID: 31073086 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Stomach | 15.1 | Medium |
| Small intestine | 18.7 | Medium |
| Colon | 22.4 | High |
| Kidney | 6.2 | Low |
| Bone marrow | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.5 | Low endogenous expression |
| HeLa | 3.2 | Moderate |
| A549 (lung cancer) | 8.7 | High |
| HCT116 (colon cancer) | 15.4 | Very high |
| MCF7 (breast cancer) | 2.1 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.614G>A (p.Arg205His) | Missense | <0.01% | Reduced proton sensitivity; loss of function |
| c.1003C>T (p.Arg335Cys) | Missense | <0.01% | Impaired G protein coupling |
| c.1270G>A (p.Glu424Lys) | Missense | <0.01% | Altered pH response threshold |
Mutation functional classification
Loss of Function (LOF)
p.Arg205His and p.Arg335Cys reduce receptor activation by protons, impairing downstream signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GPR68.
Dominant Negative (DN)
No dominant-negative mutations described for GPR68.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity (GO:0004930) | • proton binding (GO:0042301) |
| • Gq/11-coupled receptor activity (GO:0004937) | • Gs-coupled receptor activity (GO:0004938) |
| • positive regulation of cytosolic calcium ion concentration (GO:0007204) | • positive regulation of cAMP-mediated signaling (GO:0030819) |
| • inflammatory response (GO:0006954) | • bone resorption (GO:0045453) |
Pathways
• GPCR downstream signaling (Reactome R-HSA-388396)
• Gq/11 signaling (Reactome R-HSA-416476)
• Gs signaling (Reactome R-HSA-418555)
• pH sensing by OGR1 (WikiPathways WP5090)
Protein Summary
GPR68 (OGR1) is a 7-transmembrane G protein-coupled receptor of 365 amino acids. It is activated by extracellular protons (pH 6.8–7.0) and signals primarily through Gq/11, leading to phospholipase C activation, IP3 production, and calcium mobilization. It also couples to Gs, increasing cAMP. The receptor is N-glycosylated and localizes to the plasma membrane. Its structure includes a conserved DRY motif and a proton-sensing histidine cluster in extracellular loops.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPR68 Knockout HEK293 Cell Line | EDJ-KQ5475 | Human | 8111 | Details Get a Quote |
| GPR68 Knockout HeLa Cell Line | EDJ-KQ54822 | Human | 8111 | Details Get a Quote |
| GPR68 Knockout A-549 Cell Line | EDJ-KQ63313 | Human | 8111 | Details Get a Quote |
| GPR68 Knockout HCT 116 Cell Line | EDJ-KQ71784 | Human | 8111 | Details Get a Quote |
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