GPR39 Gene

HGNC Family	G protein-coupled receptors
Name	G protein-coupled receptor 39
Description	This gene is a member of the ghrelin receptor family and encodes a rhodopsin-type G-protein-coupled receptor (GPCR). The encoded protein is involved in zinc-dependent signaling in epithelial tissue in intestines, prostate and salivary glands. The protein may also be involved in the pathophysiology of depression. [provided by RefSeq, Jun 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GPR39 is a multifunctional, constitutively active G protein–coupled receptor that has emerged as a critical extracellular zinc sensor with diverse roles in physiology and disease. Early investigations proposed that GPR39 might mediate the anorexigenic effects of obestatin—a peptide encoded by the ghrelin gene—but subsequent studies have demonstrated that zinc, rather than obestatin, is the more consistent activator of its signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " Activated by extracellular Zn²⁺, GPR39 engages several downstream effectors—including the G<sub>q</sub>/phospholipase C cascade, inositol phosphate turnover, cAMP‐ and serum response element–dependent transcription, and pathways mediated by G<sub>12/13</sub>–Rho kinase—to modulate cellular function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": " In the gastrointestinal tract, GPR39 influences motility, gastric emptying, and the maintenance of epithelial barrier integrity by regulating the expression of tight junction proteins such as occludin, thereby contributing to mucosal repair and homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": " In the endocrine pancreas, GPR39 is expressed in insulin‐producing β‐cells where it helps regulate islet architecture, insulin secretion, and glucose tolerance, suggesting that modulation of its activity could have therapeutic value for type 2 diabetes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": " Moreover, in the central nervous system GPR39 contributes to neuronal excitability and survival by modulating the CREB–BDNF cascade and influencing inhibitory neurotransmission (for example, via up‐regulation of KCC2), with receptor deficiency being linked to depressive‐ and anxiety‐like behaviors and altered monoaminergic tone."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "21"}]}, {"type": "t", "text": " In addition, zinc–GPR39 signaling promotes cellular repair in epithelia such as keratinocytes, where it enhances Ca²⁺ responses and survival mechanisms involved in wound healing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}, {"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Recent evidence also implicates aberrant GPR39 expression in oncogenesis; overexpression in esophageal and oral squamous cell carcinomas promotes cell proliferation, cell cycle progression, and epithelial–mesenchymal transition through modulation of cyclins and PI3K/AKT/mTOR signaling, while microRNAs targeting GPR39 can attenuate these tumorigenic processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "25"}]}, {"type": "t", "text": " Finally, population‐based genetic studies have begun to explore associations between GPR39 polymorphisms and migraine susceptibility, further underscoring the receptor’s broad physiological impact."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": " Collectively, these findings illustrate that GPR39 functions as a zinc sensor that orchestrates a wide range of cellular responses in the gastrointestinal, endocrine, nervous, and neoplastic systems, making it an attractive target for therapeutic intervention in metabolic, neuropsychiatric, and cancer disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jian V Zhang, Pei-Gen Ren, Orna Avsian-Kretchmer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1117255"}], "href": "https://doi.org/10.1126/science.1117255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16284174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16284174"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Birgitte Holst, Kristoffer L Egerod, Enrico Schild, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPR39 signaling is stimulated by zinc ions but not by obestatin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2006-0933"}], "href": "https://doi.org/10.1210/en.2006-0933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16959833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16959833"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Erwin Lauwers, Bart Landuyt, Lutgarde Arckens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Obestatin does not activate orphan G protein-coupled receptor GPR39."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.09.141"}], "href": "https://doi.org/10.1016/j.bbrc.2006.09.141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17054911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17054911"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jian V Zhang, Holger Jahr, Chin-Wei Luo, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "microRNA-1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39-mediated PI3K/AKT/mTOR pathway in HCC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.14705"}], "href": "https://doi.org/10.1111/jcmm.14705"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31576658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31576658"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yu-Hsiang Ling, Shih-Pin Chen, Cathy Shen-Jang Fann, et al. 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Proteins	GPR39_HUMAN
NCBI Gene ID	2863
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GPR39 has 5,909 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 107 datasets.

Click the + buttons to view associations for GPR39 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GPR39 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GPR39 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of GPR39 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of GPR39 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of GPR39 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of GPR39 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GPR39 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of GPR39 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GPR39 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of GPR39 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GPR39 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of GPR39 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GPR39 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GPR39 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GPR39 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of GPR39 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GPR39 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GPR39 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GPR39 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with GPR39 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GPR39 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GPR39 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GPR39 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GPR39 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GPR39 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with GPR39 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with GPR39 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with GPR39 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with GPR39 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GPR39 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GPR39 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GPR39 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GPR39 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing GPR39 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GPR39 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with GPR39 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of GPR39 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with GPR39 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing GPR39 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of GPR39 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of GPR39 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.