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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SUCNR1
succinate receptor 1
Chromosome 3 · 3q25.1
NCBI Gene: 56670Ensembl: ENSG00000198829.7HGNC: HGNC:4542UniProt: Q9BXA5
41PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneextracellular exosomeprotein bindingG protein-coupled receptor signaling pathwayandrogenetic alopeciaovarian neoplasmalopeciacorneal ulcer
✦AI Summary

SUCNR1 encodes a G protein-coupled receptor that binds succinate and mediates diverse physiological processes through Gq/GNAQ or Gi/GNAI signaling pathways 1. The receptor serves as a critical metabolic sensor linking cellular stress, inflammation, and energy homeostasis. In macrophages, SUCNR1 exhibits context-dependent immune regulation, promoting anti-inflammatory M2 polarization through Gq signaling under normal conditions 12, while facilitating pro-inflammatory responses in activated M1 macrophages. The receptor plays important roles in cancer progression, where tumor-derived succinate activates SUCNR1 to promote macrophage polarization into tumor-associated macrophages and enhance metastasis via PI3K-HIF-1α signaling 3. In adipose tissue, SUCNR1 controls energy metabolism by regulating leptin expression through AMPK-JNK-CEBPA and circadian clock pathways 4. During exercise, muscle cells release succinate in a pH-dependent manner, which activates SUCNR1 in non-muscle cells to coordinate tissue remodeling, innervation, and strength adaptation 5. SUCNR1 also contributes to liver inflammation regulation, where elevated succinate levels can drive pathological responses in stellate cells and macrophages 6. Additionally, the receptor supports CD8+ T cell cytotoxicity through autocrine succinate signaling 7.

Sources cited
1
SUCNR1 signals through Gq/GNAQ pathways and promotes M2 macrophage polarization
PMID: 34133934
2
SUCNR1 activation promotes anti-inflammatory responses in macrophages
PMID: 30962591
3
Tumor-derived succinate activates SUCNR1 to promote cancer metastasis via PI3K-HIF-1α signaling
PMID: 31735641
4
SUCNR1 controls leptin expression through AMPK-JNK-CEBPA and circadian clock pathways
PMID: 36977414
5
Exercise-induced succinate signals via SUCNR1 to coordinate muscle remodeling
PMID: 32946811
6
SUCNR1 mediates liver inflammation in stellate cells and macrophages
PMID: 34002097
7
SUCNR1 supports CD8+ T cell cytotoxicity through autocrine succinate signaling
PMID: 35820416
Disease Associationsⓘ20
androgenetic alopeciaOpen Targets
0.22Weak
ovarian neoplasmOpen Targets
0.15Weak
alopeciaOpen Targets
0.14Weak
corneal ulcerOpen Targets
0.13Weak
skin neoplasmOpen Targets
0.12Weak
neurodegenerative diseaseOpen Targets
0.11Weak
alcohol drinkingOpen Targets
0.11Weak
heart diseaseOpen Targets
0.11Weak
joint diseaseOpen Targets
0.11Weak
type 1 diabetes mellitusOpen Targets
0.09Suggestive
Abruptio PlacentaeOpen Targets
0.09Suggestive
idiopathic pulmonary fibrosisOpen Targets
0.09Suggestive
renal cell carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
nephrotic syndromeOpen Targets
0.07Suggestive
focal segmental glomerulosclerosisOpen Targets
0.07Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
familial juvenile hyperuricemic nephropathy type 1Open Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPRC1Shared pathway100%CCDC198Shared pathway100%NPYProtein interaction77%HCAR2Protein interaction71%RENProtein interaction71%GPBAR1Shared pathway50%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
7%
Heart
4%
Lung
3%
Brain
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
SUCNR1PPRC1CCDC198NPYHCAR2RENGPBAR1
PROTEIN STRUCTURE
Preparing viewer…
PDB8YKV · 2.48 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.97LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF3.11 [0.97–1.97]
RankingsWhere SUCNR1 stands among ~20K protein-coding genes
  • #10,095of 20,598
    Most Researched41
  • #17,788of 17,882
    Most Constrained (LOEUF)1.97
Genes detectedSUCNR1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
UCP1 governs liver extracellular succinate and inflammatory pathogenesis.
PMID: 34002097
Nat Metab · 2021
1.00
2
Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor.
PMID: 31735641
Mol Cell · 2020
0.90
3
Succinate: a metabolic signal in inflammation.
PMID: 24361092
Trends Cell Biol · 2014
0.80
4
Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling.
PMID: 34133934
Cell Rep · 2021
0.70
5
Tumor cells dictate anti-tumor immune responses by altering pyruvate utilization and succinate signaling in CD8
PMID: 35820416
Cell Metab · 2022
0.60