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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GPR19
G protein-coupled receptor 19
Chromosome 12 · 12p13.1
NCBI Gene: 2842Ensembl: ENSG00000183150.9HGNC: HGNC:4473UniProt: Q15760
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
G protein-coupled receptor activityprotein bindingG protein-coupled receptor signaling pathwayplasma membraneatrial fibrillationAbnormality of the skeletal systemsystemic lupus erythematosusmathematical ability
✦AI Summary

GPR19 is a G protein-coupled receptor that functions as a multifaceted regulator of metabolism, circadian rhythms, and aging-related processes 1. The receptor serves as a pseudo-orphan GPCR with adropin as its endogenous ligand 2, mediating metabolic control through adropin-dependent signaling pathways 3. GPR19 expression is distributed across neuroendocrine tissues including pancreatic islets, intestinal ganglia, and brain cortex 4, where it coordinates stress responses and DNA damage management at varying expression levels 1. Functionally, GPR19 activation by adropin inhibits fibroblast activation and fibrosis through deactivation of TGFβ/GLI1 signaling 5, while promoting mesenchymal-epithelial transition in breast cancer via ERK/MAPK pathway activation 2. In adrenocortical cells, GPR19-mediated adropin signaling inhibits steroidogenesis through TGF-β pathway activation 6. Clinically, GPR19 shows diagnostic and prognostic significance in neuroendocrine and lung tumors, with elevated expression correlating with improved patient survival in adenocarcinomas 4. The receptor's role in aging-associated pathology positions it as a potential therapeutic target for metabolic dysfunction, fibrotic diseases, and diabetes 7.

Sources cited
1
GPR19 coordinates aging-associated metabolic dysfunction, stress response, DNA integrity management, and senescence; functions as pseudo-orphan receptor
PMID: 37239845
2
Adropin is endogenous ligand for GPR19; GPR19 activation promotes mesenchymal-epithelial transition via ERK/MAPK pathway
PMID: 28476646
3
Adropin modulates carbohydrate and lipid metabolism; lower levels in obesity and diabetes
PMID: 39888316
4
GPR19 expressed in pancreatic islets, intestinal ganglia, brain cortex; elevated in neuroendocrine tumors and lung adenocarcinomas with prognostic significance
PMID: 37923782
5
Adropin-GPR19 signaling inhibits fibroblast activation and fibrosis through deactivation of TGFβ/GLI1 signaling; GPR19 knockdown abrogates antifibrotic effects
PMID: 38536934
6
GPR19 expressed in adrenocortical cells; adropin-GPR19 signaling inhibits steroidogenesis via TGF-β pathway; elevated GPR19 in adrenocortical carcinoma
PMID: 33133015
7
GPR19 plays central role in aging process through metabolic control, circadian rhythm regulation, and stress responsiveness
PMID: 36362387
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.41Moderate
Abnormality of the skeletal systemOpen Targets
0.39Weak
systemic lupus erythematosusOpen Targets
0.32Weak
mathematical abilityOpen Targets
0.30Weak
smoking initiationOpen Targets
0.29Weak
duodenitisOpen Targets
0.26Weak
injuryOpen Targets
0.14Weak
hypertensionOpen Targets
0.09Suggestive
major depressive disorderOpen Targets
0.07Suggestive
response to xenobiotic stimulusOpen Targets
0.06Suggestive
attention deficit hyperactivity disorderOpen Targets
0.06Suggestive
obsessive-compulsive disorderOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
cardiovascular diseaseOpen Targets
0.05Suggestive
cancerOpen Targets
0.05Suggestive
adrenal cortex carcinomaOpen Targets
0.03Suggestive
Neoplasm of the lungOpen Targets
0.03Suggestive
prostate carcinomaOpen Targets
0.02Suggestive
small cell lung carcinomaOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ENHOProtein interaction90%ETV6Protein interaction74%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
37%
Lung
2%
Liver
1%
Heart
1%
Ovary
1%
Gene Interaction Network
Click a node to explore
GPR19ENHOETV6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q15760
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.74LoF Tolerant
pLIⓘ
0.05Tolerant
Observed/Expected LoF0.47 [0.31–0.74]
RankingsWhere GPR19 stands among ~20K protein-coding genes
  • #14,707of 20,598
    Most Researched18
  • #5,761of 17,882
    Most Constrained (LOEUF)0.74
Genes detectedGPR19
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Attenuation of fibroblast activation and fibrosis by adropin in systemic sclerosis.
PMID: 38536934
Sci Transl Med · 2024
1.00
2
Expression of G protein-coupled receptor GPR19 in normal and neoplastic human tissues.
PMID: 37923782
Sci Rep · 2023
0.90
3
Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process.
PMID: 36362387
Int J Mol Sci · 2022
0.80
4
G protein-coupled receptor GPR19 regulates E-cadherin expression and invasion of breast cancer cells.
PMID: 28476646
Biochim Biophys Acta Mol Cell Res · 2017
0.70
5
The levels of adropin and its therapeutic potential in diabetes.
PMID: 39888316
J Endocrinol · 2025
0.60