Details for: ENTPD7

Gene ID: 57089

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: ENTPD7

Ensembl ID: ENSG00000198018

Description: ectonucleoside triphosphate diphosphohydrolase 7

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • conjunctival epithelial cell CL1000432
    CSI 3.08
    rCSI 4.7%
    PRS 98.55
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.6
    rCSI 3.24%
    PRS 95.95
  • BEST4+ enteroycte CL4030026
    CSI 2.53
    rCSI 3.15%
    PRS 98.61
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.5
    rCSI 3.22%
    PRS 96.89
  • Langerhans cell CL0000453
    CSI 2.41
    rCSI 3.68%
    PRS 99.88
  • paneth cell of epithelium of small intestine CL1000343
    CSI 2.36
    rCSI 6.62%
    PRS 99.29
  • ependymal cell CL0000065
    CSI 2.36
    rCSI 4.79%
    PRS 93.84
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.32
    rCSI 2.81%
    PRS 99.68
  • enterocyte CL0000584
    CSI 2.06
    rCSI 3.31%
    PRS 97.95
  • small intestine goblet cell CL1000495
    CSI 1.96
    rCSI 4.3%
    PRS 99.14
  • melanocyte of skin CL1000458
    CSI 1.33
    rCSI 1.81%
    PRS 87.43
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.87
    rCSI 3.15%
    PRS 95.76

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • 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 [ENTPD7](/details-gene/57089) (Ectonucleoside Triphosphate Diphosphohydrolase 7) is a protein-coding gene located on chromosome 10q24.2. It encodes an enzyme that belongs to the ecto-nucleoside triphosphate diphosphohydrolase family, which is crucial for the catabolism of nucleotides. Functionally, [ENTPD7](/details-gene/57089) exhibits phosphatase activity towards various nucleoside triphosphates, including CTP, GTP, and UTP, playing a key role in nucleotide metabolism ([R-HSA-15869](https://reactome.org/content/detail/R-HSA-15869)). Initial molecular characterization identified it as a novel mammalian endo-apyrase, suggesting a primary function within intracellular compartments like the Golgi apparatus ([Link](https://doi.org/10.1074/jbc.m011569200)). **Overall**, expression data reveals its significance in a diverse array of cell types, including epithelial cells of the conjunctiva and intestine, specific subtypes of cortical interneurons, and professional antigen-presenting cells, suggesting a fundamental role in regulating purinergic signaling across mucosal, neural, and immune systems. ## Cellular Roles and Expression Landscape The expression profile of [ENTPD7](/details-gene/57089) indicates a broad but distinct cellular footprint across multiple major lineages, rather than being restricted to a single tissue. **Overall**, its highest significance is observed in the [conjunctival epithelial cell](/details-cell/CL1000432) (CSI: 3.08), highlighting a potentially important role in the ocular surface environment. It also shows prominent significance in two distinct functional systems: 1. **Nervous System:** [ENTPD7](/details-gene/57089) is a significant marker for specific inhibitory interneuron populations in the cortex, including [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 2.60) and [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 2.50). Its expression in [ependymal cell](/details-cell/CL0000065) (CSI: 2.36) and glutamatergic neurons further suggests a role in regulating nucleotide levels within the central nervous system. 2. **Epithelial and Mucosal Tissues:** The gene is highly significant in various specialized epithelial cells, particularly within the gastrointestinal tract. These include [BEST4+ enteroycte](/details-cell/CL4030026) (CSI: 2.53), [paneth cell of epithelium of small intestine](/details-cell/CL1000343) (CSI: 2.36), [enterocyte](/details-cell/CL0000584) (CSI: 2.06), and [small intestine goblet cell](/details-cell/CL1000495) (CSI: 1.96). This pattern points towards a key function in maintaining homeostasis at mucosal barriers. 3. **Immune System:** [ENTPD7](/details-gene/57089) is also a marker for professional antigen-presenting cells, such as the [Langerhans cell](/details-cell/CL0000453) (CSI: 2.41) in the epidermis and the [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399) (CSI: 2.32). This expression is consistent with a role in modulating immune cell function through the control of extracellular nucleotides. The diverse expression landscape suggests that [ENTPD7](/details-gene/57089) is a key enzymatic component for managing local nucleotide concentrations, a process fundamental to cell signaling, inflammation, and neurotransmission in these specialized cellular contexts. ## Pathways and Molecular Function The functional annotations for [ENTPD7](/details-gene/57089) are centered on its enzymatic role in nucleotide breakdown. As an ectonucleoside triphosphate diphosphohydrolase, its primary molecular functions include [Gtpase activity](/details-cell/GO:0003924), [Ctpase activity](/details-cell/GO:0043273), and [Udp phosphatase activity](/details-cell/GO:0045134), contributing broadly to [ribonucleoside triphosphate phosphatase activity](/details-cell/GO:0017111). These activities are part of the larger biological processes of [nucleobase-containing small molecule catabolic process](/details-cell/GO:0034656) and are categorized under the Reactome pathway [Phosphate bond hydrolysis by ntpdase proteins](/details-cell/R-HSA-8850843). Its localization to the [Golgi apparatus](/details-cell/GO:0005794) and membranes of cytoplasmic and endocytic vesicles ([GO:0030659](https://www.ebi.ac.uk/QuickGO/term/GO:0030659), [GO:0030666](https://www.ebi.ac.uk/QuickGO/term/GO:0030666)) indicates that it primarily functions within the cell's secretory pathway. This intra-organellar activity likely controls the nucleotide concentrations required for processes like glycosylation or modulates the contents of vesicles destined for secretion. By controlling nucleotide levels, [ENTPD7](/details-gene/57089) is implicated in the [regulation of immune response](/details-cell/GO:0050776), which is consistent with its expression in dendritic cells and Langerhans cells. Extracellular nucleotides like ATP act as danger signals, and their hydrolysis can terminate or modify inflammatory signaling. Notably, [ENTPD7](/details-gene/57089) is also associated with [T-helper 17 cell differentiation](/details-cell/GO:0072539), suggesting a specific role in shaping adaptive immune responses, particularly at mucosal surfaces where its expression in epithelial cells is high. ## Research Directions The widespread yet specific expression pattern of [ENTPD7](/details-gene/57089), coupled with its core enzymatic function, opens several avenues for future research into its role in health and disease. **Proposed Hypotheses:** 1. Given its high significance in multiple intestinal epithelial cell types ([BEST4+ enteroycte](/details-cell/CL4030026), [paneth cell](/details-cell/CL1000343)) and its annotated role in regulating immunity and Th17 differentiation, [ENTPD7](/details-gene/57089) likely acts as a key regulator of the gut mucosal barrier. It may control the balance between inflammatory and tolerogenic signals by hydrolyzing extracellular ATP released during cell stress or microbial translocation, thereby preventing excessive inflammation characteristic of diseases like inflammatory bowel disease. 2. The specific high expression of [ENTPD7](/details-gene/57089) in GABAergic interneurons ([pvalb GABAergic cortical interneuron](/details-cell/CL4023018), [sst GABAergic cortical interneuron](/details-cell/CL4023017)) suggests a role in neuromodulation. [ENTPD7](/details-gene/57089) may fine-tune purinergic signaling in the synaptic microenvironment by regulating the availability of ATP, which can act as a neurotransmitter or modulator, thus influencing the excitability of cortical inhibitory circuits. **Suggested Experimental Approach:** To test the first hypothesis regarding its role in intestinal homeostasis, a compelling experiment would involve a targeted knockout of [ENTPD7](/details-gene/57089) in a murine model of colitis (e.g., DSS-induced colitis). Researchers could then assess disease severity through clinical scores and histology. The intestinal tissue and lamina propria lymphocytes could be analyzed via flow cytometry to quantify Th17 cell populations and via RNA-sequencing to profile inflammatory gene expression. Additionally, measuring the concentration of extracellular ATP and its metabolites in the gut lumen would directly test whether [ENTPD7](/details-gene/57089) loss leads to an accumulation of pro-inflammatory purinergic signals. **Therapeutic Potential:** As an enzyme, [ENTPD7](/details-gene/57089) is a druggable target. Its role in modulating the immune response, particularly at mucosal barriers, makes it a potential therapeutic target for inflammatory conditions like inflammatory bowel disease or psoriasis, where Th17 cells are pathogenic. A strategy involving local delivery of a small molecule inhibitor of [ENTPD7](/details-gene/57089) could potentially enhance anti-microbial defenses by increasing local ATP, while systemic activators might be explored for their potential to reduce inflammation by promoting the generation of immunosuppressive adenosine. However, its significant expression in the central nervous system warrants caution, as systemic modulation could lead to undesirable neurological side effects, suggesting that targeted or localized therapies would be the most promising approach.

Genular Protein ID: 3327631229

Symbol: ENTP7_HUMAN

Name: Ectonucleoside triphosphate diphosphohydrolase 7

UniProtKB Accession Codes:

Q9NQZ7 B2RB83 B3KP21 D3DR64

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 22 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 7 Ensembl 1 ExpressionAtlas 1 GO 18 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 4 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11278936

Title: Molecular cloning and characterization of a novel mammalian endo-apyrase (LALP1).

PubMed ID: 11278936

DOI: 10.1074/jbc.m011569200

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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

Sequence Information:

  • Length: 604
  • Mass: 68960
  • Checksum: 6B73997A8AB318D8
  • Sequence:
    • MARISFSYLC PASWYFTVPT VSPFLRQRVA FLGLFFISCL LLLMLIIDFR HWSASLPRDR 
QYERYLARVG ELEATDTEDP NLNYGLVVDC GSSGSRIFVY FWPRHNGNPH DLLDIKQMRD 
RNSQPVVKKI KPGISAMADT PEHASDYLRP LLSFAAAHVP VKKHKETPLY ILCTAGMRLL 
PERKQLAILA DLVKDLPLEF DFLFSQSQAE VISGKQEGVY AWIGINFVLG RFDHEDESDA 
EATQELAAGR RRTVGILDMG GASLQIAYEV PTSTSVLPAK QEEAAKILLA EFNLGCDVQH 
TEHVYRVYVT TFLGFGGNFA RQRYEDLVLN ETLNKNRLLG QKTGLSPDNP FLDPCLPVGL 
TDVVERNSQV LHVRGRGDWV SCGAMLSPLL ARSNTSQASL NGIYQSPIDF NNSEFYGFSE 
FFYCTEDVLR IGGRYHGPTF AKAAQDYCGM AWSVLTQRFK NGLFSSHADE HRLKYQCFKS 
AWMYQVLHEG FHFPYDYPNL RTAQLVYDRE VQWTLGAILY KTRFLPLRDL RQEGVRQAHG 
SWFRLSFVYN HYLFFACILV VLLAIFLYLL RLRRIHHRQT RASAPLDLLW LEEVVPMMGV 
QVGP