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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GPR119
G protein-coupled receptor 119
Chromosome X · Xq26.1
NCBI Gene: 139760Ensembl: ENSG00000147262.5HGNC: HGNC:19060UniProt: Q8TDV5
33PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
signaling receptor complexprotein bindingadenylate cyclase-activating G protein-coupled receptor signaling pathwaycytoplasmneurodegenerative diseasetype 2 diabetes mellitusDisorder of lipid metabolismtype 1 diabetes mellitus
✦AI Summary

GPR119 is a G protein-coupled receptor that functions as a metabolic regulator with dual roles in glucose homeostasis and lipid sensing. The receptor is predominantly expressed in pancreatic β-cells and enteroendocrine cells, where it mediates glucose-dependent insulin secretion and incretin release 1. GPR119 serves as a 'fat sensor' that responds to endogenous lipid ligands including oleoylethanolamide (OEA), lysophosphatidylcholine (LPC), and 2-oleoylglycerol 23. Upon activation, GPR119 signals through Gs-mediated pathways to activate adenylyl cyclase, leading to increased cAMP levels 1. Recent studies demonstrate that microbiota-derived LPC acts through GPR119 to suppress ferroptosis and ameliorate Alzheimer's disease pathology by inhibiting ACSL4 expression 4. Conversely, in non-alcoholic steatohepatitis, 2-oleoylglycerol activation of GPR119 triggers the TAK1/NF-κB/TGF-β1 signaling pathway, promoting liver inflammation and fibrosis 5. Despite its therapeutic potential for type 2 diabetes treatment, no synthetic GPR119 ligands have progressed beyond phase II clinical trials 1. The receptor's structure has been elucidated through cryo-electron microscopy, providing insights for future drug development 6.

Sources cited
1
GPR119 mediates glucose-dependent insulin secretion and incretin release, making it a promising diabetes target
PMID: 28722242
2
GPR119 functions as a 'fat sensor' responding to oleic acid-containing lipids including OEA and 2-oleoylglycerol
PMID: 22560300
3
OEA and palmitoylethanolamide are physiological ligands for GPR119 with various metabolic effects
PMID: 33494185
4
Microbiota-derived LPC acts through GPR119 to suppress ferroptosis and ameliorate Alzheimer's disease
PMID: 39510074
5
2-oleoylglycerol activates GPR119/TAK1/NF-κB/TGF-β1 pathway promoting liver inflammation in NASH
PMID: 36646715
6
GPR119 structure has been determined by cryo-EM providing basis for drug development
PMID: 38288442
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.30Weak
type 2 diabetes mellitusOpen Targets
0.11Weak
Disorder of lipid metabolismOpen Targets
0.08Suggestive
type 1 diabetes mellitusOpen Targets
0.08Suggestive
diabetes mellitusOpen Targets
0.08Suggestive
gastric adenocarcinomaOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.06Suggestive
cancerOpen Targets
0.05Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.05Suggestive
hypoinsulinemic hypoglycemia and body hemihypertrophyOpen Targets
0.05Suggestive
hyperinsulinemic hypoglycemia, familial, 1Open Targets
0.04Suggestive
exercise-induced hyperinsulinismOpen Targets
0.04Suggestive
hyperinsulinism due to glucokinase deficiencyOpen Targets
0.04Suggestive
hyperinsulinism-hyperammonemia syndromeOpen Targets
0.04Suggestive
hyperinsulinemic hypoglycemia, familial, 2Open Targets
0.04Suggestive
hyperproinsulinemiaOpen Targets
0.04Suggestive
obesity due to prohormone convertase I deficiencyOpen Targets
0.03Suggestive
insulinomaOpen Targets
0.03Suggestive
HypoglycemiaOpen Targets
0.03Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
GSK-1292263Phase II
Glucose-dependent insulinotropic receptor agonist
gastric adenocarcinoma
MBX-2982Phase II
Glucose-dependent insulinotropic receptor agonist
diabetes mellitus
Related Genes
GPR26Shared pathway100%GPR78Shared pathway100%GPHB5Shared pathway100%FFAR4Protein interaction96%GNASProtein interaction95%GPR55Protein interaction92%
Tissue Expression6 tissues
Lung
0%
Brain
0%
Bone Marrow
0%
Ovary
0%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
GPR119GPR26GPR78GPHB5FFAR4GNASGPR55
PROTEIN STRUCTURE
Preparing viewer…
PDB7WCM · 2.33 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.99LoF Tolerant
pLIⓘ
0.06Tolerant
Observed/Expected LoF0.53 [0.30–0.99]
RankingsWhere GPR119 stands among ~20K protein-coding genes
  • #11,345of 20,598
    Most Researched33
  • #9,531of 17,882
    Most Constrained (LOEUF)0.99
Genes detectedGPR119
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Gut microbiome and health: mechanistic insights.
PMID: 35105664
Gut · 2022
1.00
2
Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathology via suppressing ferroptosis.
PMID: 39510074
Cell Metab · 2025
0.90
3
Novel cannabinoid receptors.
PMID: 17906678
Br J Pharmacol · 2007
0.80
4
Therapeutic application of GPR119 ligands in metabolic disorders.
PMID: 28722242
Diabetes Obes Metab · 2018
0.70
5
Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol.
PMID: 36646715
Nat Commun · 2023
0.60