Details for: GPR39

Gene ID: 2863

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GPR39

Ensembl ID: ENSG00000183840

Description: G protein-coupled receptor 39

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pulmonary alveolar type 2 cell CL0002063
    CSI 7.18
    rCSI 11.13%
    PRS 92.76
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 6.53
    rCSI 10.96%
    PRS 80.68
  • respiratory basal cell CL0002633
    CSI 6.34
    rCSI 6.57%
    PRS 93.35
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 5.86
    rCSI 6.77%
    PRS 85.23
  • kidney connecting tubule epithelial cell CL1000768
    CSI 5.11
    rCSI 12.96%
    PRS 86.98
  • ependymal cell CL0000065
    CSI 4.97
    rCSI 10.09%
    PRS 76.04
  • BEST4+ enteroycte CL4030026
    CSI 4.64
    rCSI 5.77%
    PRS 91.63
  • sncg GABAergic cortical interneuron CL4023015
    CSI 4.03
    rCSI 6.49%
    PRS 81.72
  • lung secretory cell CL1000272
    CSI 3.97
    rCSI 9.82%
    PRS 92.91
  • glioblast CL0000030
    CSI 3.83
    rCSI 6.11%
    PRS 85.34
  • renal principal cell CL0005009
    CSI 3.79
    rCSI 9.86%
    PRS 91.6
  • brush cell of tracheobronchial tree CL0002075
    CSI 3.69
    rCSI 10.96%
    PRS 96.41
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.69
    rCSI 2.86%
    PRS 93.98
  • epithelial cell of proximal tubule CL0002306
    CSI 3.46
    rCSI 8.44%
    PRS 86.45
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.3
    rCSI 7.4%
    PRS 80.89
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 3.14
    rCSI 11.86%
    PRS 80.86
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 3.09
    rCSI 4.38%
    PRS 90.46
  • Mueller cell CL0000636
    CSI 3.08
    rCSI 7.03%
    PRS 86.46
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.94
    rCSI 7.61%
    PRS 89.99
  • hepatocyte CL0000182
    CSI 2.94
    rCSI 5.26%
    PRS 90.63
  • lung neuroendocrine cell CL1000223
    CSI 2.79
    rCSI 4.13%
    PRS 93.16
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 2.72
    rCSI 7.33%
    PRS 93.85
  • retinal pigment epithelial cell CL0002586
    CSI 2.54
    rCSI 5.04%
    PRS 89.1
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.47
    rCSI 8.9%
    PRS 78.79
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.22
    rCSI 2.66%
    PRS 80.69
  • renal beta-intercalated cell CL0002201
    CSI 2.09
    rCSI 4.98%
    PRS 92.23
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.09
    rCSI 4.6%
    PRS 94.2
  • conjunctival epithelial cell CL1000432
    CSI 2.06
    rCSI 3.15%
    PRS 91.12
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.04
    rCSI 4.64%
    PRS 85.64
  • parietal epithelial cell CL1000452
    CSI 1.85
    rCSI 4.93%
    PRS 87.7
  • retinal ganglion cell CL0000740
    CSI 1.84
    rCSI 4.06%
    PRS 82.88
  • basal cell of epidermis CL0002187
    CSI 1.79
    rCSI 3.17%
    PRS 64.87
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 1.76
    rCSI 15.22%
    PRS 87.28
  • lung ciliated cell CL1000271
    CSI 1.67
    rCSI 1.93%
    PRS 87.16
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.46
    rCSI 4.08%
    PRS 94.45
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.03
    rCSI 5.95%
    PRS 89.76
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.95
    rCSI 10.01%
    PRS 88.8
  • central nervous system neuron CL2000029
    CSI 0.91
    rCSI 6.67%
    PRS 84.81
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.57
    rCSI 13.73%
    PRS 78.61
  • direct pathway medium spiny neuron CL4023026
    CSI 0.41
    rCSI 9.84%
    PRS 78.49

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GPR39](/details-gene/2863) is a protein-coding gene located on chromosome 2 that encodes G protein-coupled receptor 39, a member of the rhodopsin-like receptor family. Functionally, it is recognized as a receptor for zinc ions (Zn2+) and is involved in various G protein-coupled signaling pathways, including G alpha (q) and G alpha (s) signaling. Expression data highlights its significant role in specific epithelial and neural cell populations. **Overall**, [GPR39](/details-gene/2863) shows the highest significance in [pulmonary alveolar type 2 cell](/details-cell/CL0002063), various neuronal subtypes such as [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011), and specialized kidney epithelial cells like the [kidney connecting tubule epithelial cell](/details-cell/CL1000768), suggesting its involvement in cellular sensing, secretion, and maintenance functions within these tissues. ## Cellular Roles and Expression Landscape The expression profile of [GPR39](/details-gene/2863) points to a specialized role in distinct cell types across multiple organ systems. Its most significant expression is observed in cells of the respiratory system, central nervous system, and kidneys. In the lungs, [GPR39](/details-gene/2863) is a key marker for [pulmonary alveolar type 2 cell](/details-cell/CL0002063) (CSI: 7.18), [respiratory basal cell](/details-cell/CL0002633) (CSI: 6.34), and [lung secretory cell](/details-cell/CL1000272) (CSI: 3.97). This pattern suggests a role in pulmonary homeostasis, potentially related to surfactant production, epithelial barrier integrity, and regenerative processes within the alveolar and tracheobronchial lining. Within the central nervous system, [GPR39](/details-gene/2863) shows high significance in specific inhibitory interneurons, including [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 6.53) and [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 4.03). It is also highly expressed in progenitor cells like the [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) (CSI: 5.86) and supportive glial cells such as [ependymal cell](/details-cell/CL0000065) (CSI: 4.97) and [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 3.30). This diverse neural expression suggests it may modulate neuronal excitability, neurodevelopment, and glial function. In renal tissues, [GPR39](/details-gene/2863) is prominent in epithelial cells of the nephron, including [kidney connecting tubule epithelial cell](/details-cell/CL1000768) (CSI: 5.11), [renal principal cell](/details-cell/CL0005009) (CSI: 3.79), and [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 3.46). This localization implies a function in regulating ion and solute transport and maintaining tubular integrity. ## Pathways and Molecular Function [GPR39](/details-gene/2863) is a G protein-coupled receptor integral to the [plasma membrane](/details-ontology/GO:0005886), where it participates in signal transduction. Its primary molecular function is [G protein-coupled receptor activity](/details-ontology/GO:0004930), initiating intracellular signaling cascades upon ligand binding. As a member of the [Class a/1 (rhodopsin-like receptors)](/details-pathway/R-HSA-373076) family, it is known to couple with multiple G-protein subtypes, activating downstream pathways such as [G alpha (q) signalling events](/details-pathway/R-HSA-416476) and [G alpha (s) signalling events](/details-pathway/R-HSA-418555). A key feature of [GPR39](/details-gene/2863) is its role as a sensor for extracellular zinc, consistent with its annotated function in [metal ion binding](/details-ontology/GO:0046872). Studies have demonstrated that Zn2+ acts as an agonist, triggering signaling that can protect cells from death and promote epithelial repair ([Link](https://doi.org/10.1074/jbc.m704323200), [Link](https://doi.org/10.1074/jbc.m110.107490)). Furthermore, research suggests that [GPR39](/details-gene/2863) can form heteroreceptor complexes with other GPCRs, such as serotonin and galanin receptors, potentially diversifying its signaling output ([Link](https://doi.org/10.1016/j.bbadis.2015.09.003)). ## Research Directions The specific expression patterns of [GPR39](/details-gene/2863) combined with its function as a zinc-sensing receptor open several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in [pulmonary alveolar type 2 cell](/details-cell/CL0002063) and its documented role in zinc-mediated epithelial repair ([Link](https://doi.org/10.1074/jbc.m110.107490)), [GPR39](/details-gene/2863) activation is likely a critical mechanism for sensing tissue damage (via zinc release from necrotic cells) and initiating alveolar regeneration and surfactant secretion following lung injury. 2. The high expression of [GPR39](/details-gene/2863) in distinct GABAergic interneuron subtypes ([lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)) suggests that it acts as a neuromodulator. Fluctuations in synaptic zinc levels may activate [GPR39](/details-gene/2863) to fine-tune inhibitory signaling and cortical network activity, potentially by altering the function of other co-expressed receptors. **Experimental Approach:** To test the role of [GPR39](/details-gene/2863) in alveolar repair (Hypothesis 1), one could utilize an *in vitro* organoid model. CRISPR-Cas9 could be used to generate [GPR39](/details-gene/2863)-knockout and wild-type human alveolar organoids derived from induced pluripotent stem cells. These organoids could be subjected to mechanical or chemical injury. The impact of [GPR39](/details-gene/2863) on repair would be assessed by quantifying the rate of wound closure via live-cell imaging and measuring the expression of proliferation markers (e.g., Ki67) and surfactant proteins (e.g., SFTPC) in the presence and absence of supplemental zinc. **Therapeutic Potential:** As a cell surface G protein-coupled receptor with pro-survival and tissue-reparative functions, [GPR39](/details-gene/2863) represents an attractive therapeutic target. Activation, rather than inhibition, is the likely therapeutic strategy. The development of selective small-molecule agonists for [GPR39](/details-gene/2863) could offer novel treatments for conditions characterized by epithelial damage, such as acute respiratory distress syndrome (ARDS), inflammatory bowel disease, or chronic kidney disease, by promoting endogenous repair mechanisms in a targeted manner.

Genular Protein ID: 1986295059

Symbol: GPR39_HUMAN

Name: G-protein coupled receptor 39

UniProtKB Accession Codes:

O43194 B2RC12 B6V9G4 Q08AS2 Q53R01

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 2 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugCentral 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9441746

Title: Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors.

PubMed ID: 9441746

DOI: 10.1006/geno.1997.5069

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18693759

Title: A second disulfide bridge from the N-terminal domain to extracellular loop 2 dampens receptor activity in GPR39.

PubMed ID: 18693759

DOI: 10.1021/bi8005016

PubMed ID: 18588883

Title: Molecular mechanism of Zn2+ agonism in the extracellular domain of GPR39.

PubMed ID: 18588883

DOI: 10.1016/j.febslet.2008.06.030

PubMed ID: 18180304

Title: The constitutively active orphan G-protein-coupled receptor GPR39 protects from cell death by increasing secretion of pigment epithelium-derived growth factor.

PubMed ID: 18180304

DOI: 10.1074/jbc.m704323200

PubMed ID: 20522546

Title: Zinc released from injured cells is acting via the Zn2+-sensing receptor, ZnR, to trigger signaling leading to epithelial repair.

PubMed ID: 20522546

DOI: 10.1074/jbc.m110.107490

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 26365466

Title: The zinc binding receptor GPR39 interacts with 5-HT1A and GalR1 to form dynamic heteroreceptor complexes with signaling diversity.

PubMed ID: 26365466

DOI: 10.1016/j.bbadis.2015.09.003

Sequence Information:

  • Length: 453
  • Mass: 51329
  • Checksum: 8E3A233420D9021E
  • Sequence:
    • MASPSLPGSD CSQIIDHSHV PEFEVATWIK ITLILVYLII FVMGLLGNSA TIRVTQVLQK 
KGYLQKEVTD HMVSLACSDI LVFLIGMPME FYSIIWNPLT TSSYTLSCKL HTFLFEACSY 
ATLLHVLTLS FERYIAICHP FRYKAVSGPC QVKLLIGFVW VTSALVALPL LFAMGTEYPL 
VNVPSHRGLT CNRSSTRHHE QPETSNMSIC TNLSSRWTVF QSSIFGAFVV YLVVLLSVAF 
MCWNMMQVLM KSQKGSLAGG TRPPQLRKSE SEESRTARRQ TIIFLRLIVV TLAVCWMPNQ 
IRRIMAAAKP KHDWTRSYFR AYMILLPFSE TFFYLSSVIN PLLYTVSSQQ FRRVFVQVLC 
CRLSLQHANH EKRLRVHAHS TTDSARFVQR PLLFASRRQS SARRTEKIFL STFQSEAEPQ 
SKSQSLSLES LEPNSGAKPA NSAAENGFQE HEV