SUCNR1 (Succinate Receptor 1)
G protein-coupled receptor for succinate; roles in metabolism, inflammation, and hypertension
Gene Information Card
| Symbol | SUCNR1 |
|---|---|
| Full Name | Succinate Receptor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q25.1 |
| NCBI Gene ID | 56670 ncbi.nlm.nih.gov/gene/56670 |
| Ensembl ID | ENSG00000198829 |
| UniProt ID | Q9BXA5 |
| OMIM ID | 606381 |
| HGNC ID | 17810 |
| Aliases | GPR91, P2RY13 |
Description
SUCNR1 (Succinate Receptor 1) encodes a G protein-coupled receptor (GPCR) that binds extracellular succinate, a tricarboxylic acid cycle intermediate. Activation of SUCNR1 triggers intracellular signaling via Gq/11 and Gi/o proteins, leading to calcium mobilization and MAPK pathway activation. The receptor is involved in metabolic regulation, inflammatory responses, blood pressure control, and cellular stress sensing. It is expressed in kidney, liver, adipose tissue, immune cells, and retina.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertension | Succinate-mediated SUCNR1 activation in renal juxtaglomerular cells stimulates renin release, increasing blood pressure. | PMID: 18614766 |
| Obesity and insulin resistance | SUCNR1 signaling in adipose tissue promotes adipogenesis and modulates glucose homeostasis; altered expression linked to metabolic syndrome. | PMID: 23505218 |
| Inflammatory bowel disease (IBD) | Succinate activates SUCNR1 on immune cells (dendritic cells, macrophages) to produce pro-inflammatory cytokines, exacerbating colitis. | PMID: 28068329 |
| Retinal ischemia | SUCNR1 activation in retinal ganglion cells contributes to excitotoxicity and neuronal damage during ischemic stress. | PMID: 20018723 |
| Rheumatoid arthritis | Succinate accumulation in inflamed joints activates SUCNR1 on synovial fibroblasts, promoting IL-1β production and joint destruction. | PMID: 28104835 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 8.2 | High |
| Liver | 5.1 | Medium |
| Adipose tissue | 4.8 | Medium |
| Spleen | 3.9 | Medium |
| Lung | 2.5 | Low |
| Retina | 6.7 | High |
| Small intestine | 3.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 12.5 | Overexpressed in recombinant studies |
| THP-1 (monocytes) | 7.8 | Endogenous expression |
| HepG2 (hepatocytes) | 4.3 | Moderate expression |
| 3T3-L1 (adipocytes) | 6.1 | Differentiation-dependent |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.119G>A (p.Arg40His) | Missense | <0.01% | Reduced succinate binding affinity in vitro |
| c.556C>T (p.Arg186Trp) | Missense | <0.01% | Impaired G protein coupling |
| c.832G>A (p.Gly278Ser) | Missense | <0.01% | Altered receptor trafficking |
Mutation functional classification
Loss of Function (LOF)
p.Arg40His and p.Arg186Trp reduce ligand binding or signaling.
Gain of Function (GOF)
No confirmed gain-of-function variants reported.
Dominant Negative (DN)
Not described for SUCNR1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Succinate signaling via SUCNR1 (Reactome: R-HSA-418594)
• GPCR downstream signaling (Reactome: R-HSA-388396)
• Renin-angiotensin system (KEGG: hsa04614)
Protein Summary
SUCNR1 (also known as GPR91) is a 330-amino acid G protein-coupled receptor with seven transmembrane domains. It is activated by extracellular succinate at micromolar concentrations. The receptor couples primarily to Gq/11, leading to phospholipase C activation and intracellular calcium release, and to Gi/o, inhibiting cAMP production. SUCNR1 is expressed in kidney, liver, adipose tissue, immune cells, and retina, where it mediates metabolic, inflammatory, and cardiovascular functions. Structural studies reveal a binding pocket for succinate involving residues Arg99, Arg252, and His103. The receptor is a target for therapeutic intervention in hypertension, metabolic disorders, and inflammatory diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SUCNR1 Knockout A-549 Cell Line | EDJ-KQ65252 | Human | 56670 | Details Get a Quote |
| SUCNR1 Knockout HeLa Cell Line | EDJ-KQ56749 | Human | 56670 | Details Get a Quote |
| SUCNR1 Knockout HCT 116 Cell Line | EDJ-KQ17950 | Human | 56670 | Details Get a Quote |
| SUCNR1 Knockout HEK293 Cell Line | EDJ-KQ1796 | Human | 56670 | Details Get a Quote |
