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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GPR39
G protein-coupled receptor 39
Chromosome 2 · 2q21.2
NCBI Gene: 2863Ensembl: ENSG00000183840.8HGNC: HGNC:4496UniProt: O43194
62PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingGO:0030641G protein-coupled receptor activityplasma membranesmoking initiationpoisoningdiabetes mellitusinfectious meningitis
✦AI Summary

GPR39 (G protein-coupled receptor 39) functions as a zinc-sensing receptor that detects physiological changes in extracellular Zn2+ concentrations and mediates diverse cellular responses 1. The receptor is widely expressed across multiple tissues including pancreas, gastrointestinal tract, liver, skin, and brain, where it activates Gαq, Gαs, and Gα12/13 signaling pathways 2. GPR39 plays critical roles in metabolic regulation, with evidence showing its involvement in glucose homeostasis through pancreatic beta cell function, where it is regulated by transcription factors HNF1A 3. In cardiac tissue, GPR39 serves as a receptor for GPNMB protein from bone marrow-derived macrophages, mediating post-myocardial infarction repair by enhancing myocyte contraction and reducing fibroblast activation 4. The receptor demonstrates significant anti-inflammatory properties by modulating NF-κB and MAPK signaling cascades, inhibiting inflammatory mediator release, and promoting tissue repair in conditions including neuroinflammation, pancreatitis, and inflammatory bowel disease 2. Additionally, GPR39 contributes to neuroprotection and mood regulation through interactions with neurotransmitter systems and BDNF signaling 5, and supports muscle homeostasis by counteracting glucocorticoid-induced atrophy via the obestatin signaling pathway 6. These diverse functions position GPR39 as a promising therapeutic target for multiple disease conditions 7.

Sources cited
1
GPR39 functions as zinc-sensing receptor activated by physiological Zn2+ concentrations
PMID: 33918078
2
GPR39 is widely expressed and activates multiple G-protein signaling pathways with anti-inflammatory properties
PMID: 40499698
3
GPR39 expression in pancreatic beta cells is regulated by HNF1A transcription factor
PMID: 38909044
4
GPR39 serves as receptor for GPNMB in cardiac repair after myocardial infarction
PMID: 39455836
5
GPR39 contributes to neuroprotection and mood regulation through BDNF signaling
PMID: 33632103
6
GPR39 supports muscle homeostasis through obestatin signaling pathway
PMID: 33687156
7
GPR39 represents a promising therapeutic target for multiple diseases
PMID: 39549543
Disease Associationsⓘ20
smoking initiationOpen Targets
0.41Moderate
poisoningOpen Targets
0.29Weak
diabetes mellitusOpen Targets
0.24Weak
infectious meningitisOpen Targets
0.19Weak
musculoskeletal system diseaseOpen Targets
0.17Weak
hypertrophic cardiomyopathyOpen Targets
0.16Weak
breast cancerOpen Targets
0.08Suggestive
AnxietyOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
MODYOpen Targets
0.07Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.06Suggestive
exercise-induced hyperinsulinismOpen Targets
0.05Suggestive
hyperinsulinemic hypoglycemia, familial, 2Open Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
chronic pancreatitisOpen Targets
0.05Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.05Suggestive
hyperproinsulinemiaOpen Targets
0.05Suggestive
Infundibulopelvic stenosis - multicystic kidneyOpen Targets
0.05Suggestive
infundibulopelvic stenosis-multicystic kidney syndromeOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GHRLProtein interaction99%LYPD1Protein interaction90%MLNProtein interaction84%MBOAT4Protein interaction81%
Tissue Expression6 tissues
Liver
100%
Lung
34%
Brain
3%
Bone Marrow
2%
Ovary
1%
Heart
0%
Gene Interaction Network
Click a node to explore
GPR39GHRLLYPD1MLNMBOAT4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O43194
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.65LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.17 [0.84–1.65]
RankingsWhere GPR39 stands among ~20K protein-coding genes
  • #7,465of 20,598
    Most Researched62
  • #15,874of 17,882
    Most Constrained (LOEUF)1.65
Genes detectedGPR39
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.
PMID: 38909044
Nat Commun · 2024
1.00
2
The pathophysiological functions and therapeutic potential of GPR39: Focus on agonists and antagonists.
PMID: 39549543
Int Immunopharmacol · 2024
0.90
3
Bone-marrow macrophage-derived GPNMB protein binds to orphan receptor GPR39 and plays a critical role in cardiac repair.
PMID: 39455836
Nat Cardiovasc Res · 2024
0.80
4
The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target.
PMID: 33918078
Int J Mol Sci · 2021
0.70
5
The Zinc Sensing Receptor, ZnR/GPR39, in Health and Disease.
PMID: 29389900
Int J Mol Sci · 2018
0.60