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ENTPD3 ectonucleoside triphosphate diphosphohydrolase 3 [ Homo sapiens (human) ]

Gene ID: 956, updated on 5-Aug-2026
Official Symbol
ENTPD3provided by HGNC
Official Full Name
ectonucleoside triphosphate diphosphohydrolase 3provided by HGNC
Primary source
HGNC:HGNC:3365
See related
Ensembl:ENSG00000168032 MIM:603161; AllianceGenome:HGNC:3365
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HB6; CD39L3; NTPDase-3
Summary
This gene encodes a plasma membrane-bound divalent cation-dependent E-type nucleotidase. The encoded protein is involved in the regulation of extracellular levels of ATP by hydrolysis of it and other nucleotides. Multiple transcript variants have been described. [provided by RefSeq, May 2014]
Expression
Broad expression in urinary bladder (RPKM 4.1), thyroid (RPKM 2.0) and 20 other tissues See more
Orthologs
all
Try the new Gene page
Try the new Transcripts and proteins table
See ENTPD3 in Genome Data Viewer
Location:
3p22.1
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (40387184..40428744)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (40402253..40443812)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (40428675..40470235)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19714 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14230 Neighboring gene Sharpr-MPRA regulatory region 12551 Neighboring gene eukaryotic translation initiation factor 1B Neighboring gene phosphoglycerate mutase 1 pseudogene 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19715 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14231 Neighboring gene ENTPD3, EIF1B and MYRIP antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:40459610-40459810 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19716 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19717 Neighboring gene Sharpr-MPRA regulatory region 7904 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14232 Neighboring gene Sharpr-MPRA regulatory region 106 Neighboring gene ribosomal protein L14 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19718 Neighboring gene zinc finger protein 619

Go to nucleotide: Graphics FASTA GenBank

Related articles in PubMed

  1. ENTPD3 Marks Mature Stem Cell-Derived β-Cells Formed by Self-Aggregation In Vitro. Docherty FM, et al. Diabetes, 2021 Nov. PMID 34380694, Free PMC Article
  2. Cloning, sequencing, and expression of a human brain ecto-apyrase related to both the ecto-ATPases and CD39 ecto-apyrases1. Smith TM, et al. Biochim Biophys Acta, 1998 Jul 28. PMID 9675246
  3. Mutagenesis of two conserved tryptophan residues of the E-type ATPases: inactivation and conversion of an ecto-apyrase to an ecto-NTPase. Smith TM, et al. Biochemistry, 1999 May 4. PMID 10231536
  4. Site-directed mutagenesis of human nucleoside triphosphate diphosphohydrolase 3: the importance of residues in the apyrase conserved regions. Yang F, et al. Biochemistry, 2001 Apr 3. PMID 11300774
  5. Characterization of disulfide bonds in human nucleoside triphosphate diphosphohydrolase 3 (NTPDase3): implications for NTPDase structural modeling. Ivanenkov VV, et al. Biochemistry, 2005 Jun 28. PMID 15966724

See all (21) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Silencing NTPDase3 activity rehabilitates the osteogenic commitment of post-menopausal stem cell bone progenitors.
    Title: Silencing NTPDase3 activity rehabilitates the osteogenic commitment of post-menopausal stem cell bone progenitors.
  2. ENTPD3 Marks Mature Stem Cell-Derived beta-Cells Formed by Self-Aggregation In Vitro.
    Title: ENTPD3 Marks Mature Stem Cell-Derived β-Cells Formed by Self-Aggregation In Vitro.
  3. NTPDase2 and -3 are ecto-enzymes expressed in the enteric nervous system. Both enzymes confer protection against gut inflammation in experimental colitis and exhibit alterations in Crohn's disease. These observations suggest that purinergic signalling modulated by E-NTPDases governs neuro-immune interactions that are relevant in Crohn's disease.
    Title: Expression of Ecto-nucleoside Triphosphate Diphosphohydrolases-2 and -3 in the Enteric Nervous System Affects Inflammation in Experimental Colitis and Crohn's Disease.
  4. Despite the increased level of NTPDase1 and NTPDase3 mRNA expression in chondrogenically induced MSCs, their activity toward ATP remains quite low.
    Title: Chondrogenic Differentiation of Human Mesenchymal Stem Cells Results in Substantial Changes of Ecto-Nucleotides Metabolism.
  5. NTPDase3 is the major ectonucleotidase in pancreatic beta-cells in multiple species and modulates insulin secretion by controlling activation of purinergic receptors.
    Title: Ectonucleotidase NTPDase3 is abundant in pancreatic β-cells and regulates glucose-induced insulin secretion.
  6. Cystic fibrosis epithelia exhibit >50% lower NTPDase1 activity, protein, and mRNA levels than normal epithelia, whereas these parameters are threefold higher for NTPDase3.
    Title: Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 (CD39) and NTPDase3.
  7. Generation of a helical model for NTPDase3 suggests the importance of putative hydrogen bond interactions of conserved polar residues which are critical for enzyme expression, activity, and its susceptibility to membrane perturbations.
    Title: Conserved polar residues stabilize transmembrane domains and promote oligomerization in human nucleoside triphosphate diphosphohydrolase 3.
  8. efficiently inhibit the NTPDase3expressed in insulin secreting human pancreatic islet cells in situ
    Title: Characterization of a monoclonal antibody as the first specific inhibitor of human NTP diphosphohydrolase-3 : partial characterization of the inhibitory epitope and potential applications.
  9. NTPDase3 sequence revealed a high degree of structural fold similarity with a bacterial exopolyphosphatase
    Title: Characterization of disulfide bonds in human nucleoside triphosphate diphosphohydrolase 3 (NTPDase3): implications for NTPDase structural modeling.
Submit: New GeneRIF Correction

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ93839

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ADP phosphatase activity EXP
Inferred from Experiment
more info
 PubMed 
enables ADP phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables ATP hydrolysis activity EXP
Inferred from Experiment
more info
 PubMed 
enables ATP hydrolysis activity IEA
Inferred from Electronic Annotation
more info
  
enables CDP phosphatase activity EXP
Inferred from Experiment
more info
 PubMed 
enables CDP phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables CTPase activity EXP
Inferred from Experiment
more info
 PubMed 
enables CTPase activity IEA
Inferred from Electronic Annotation
more info
  
enables GDP phosphatase activity EXP
Inferred from Experiment
more info
 PubMed 
enables GDP phosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables GDP phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables GTPase activity EXP
Inferred from Experiment
more info
 PubMed 
enables GTPase activity IEA
Inferred from Electronic Annotation
more info
  
enables IDP phosphatase activity EXP
Inferred from Experiment
more info
 PubMed 
enables IDP phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables ITPase activity EXP
Inferred from Experiment
more info
 PubMed 
enables ITPase activity IEA
Inferred from Electronic Annotation
more info
  
enables UDP phosphatase activity EXP
Inferred from Experiment
more info
 PubMed 
enables UDP phosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables UDP phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables apyrase activity EXP
Inferred from Experiment
more info
 PubMed 
enables apyrase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables apyrase activity IEA
Inferred from Electronic Annotation
more info
  
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables nucleoside diphosphate phosphatase activity EXP
Inferred from Experiment
more info
 PubMed 
enables nucleoside diphosphate phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables nucleoside diphosphate phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables pyrophosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables ribonucleoside triphosphate phosphatase activity EXP
Inferred from Experiment
more info
 PubMed 
enables ribonucleoside triphosphate phosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ribonucleoside triphosphate phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ribonucleoside triphosphate phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in nucleoside diphosphate catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ribonucleoside diphosphate catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ribonucleoside diphosphate catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in ribonucleoside triphosphate catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ribonucleoside triphosphate catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ribonucleoside triphosphate catabolic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in plasma membrane EXP
Inferred from Experiment
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
Preferred Names
ectonucleoside triphosphate diphosphohydrolase 3
Names
CD39 antigen-like 3
NTPDase 3
eNTPDase-3
ecto-ATP diphosphohydrolase 3
ecto-ATPDase 3
ecto-ATPase 3
ecto-apyrase 3
NP_001239.2
NP_001278889.1
NP_001278890.1
XP_011532568.1
XP_054204452.1

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_047041.1 RefSeqGene

    Range
    5029..46589
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001248.4 → NP_001239.2  ectonucleoside triphosphate diphosphohydrolase 3 isoform 1

    See identical proteins and their annotated locations for NP_001239.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same protein (isoform 1).
    Source sequence(s)
    AC104186, AF039917, DA209533
    Consensus CDS
    CCDS2691.1
    UniProtKB/Swiss-Prot
    B2R8D0, G5E9N0, O60495, O75355, Q8N6K2
    UniProtKB/TrEMBL
    A0ACI8QTZ0
    Related
    ENSP00000301825.3, ENST00000301825.8
    Conserved Domains (1) summary
    cl17037
    Location:56 → 478
    NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily

  2. NM_001291960.2 → NP_001278889.1  ectonucleoside triphosphate diphosphohydrolase 3 isoform 1

    See identical proteins and their annotated locations for NP_001278889.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer protein (isoform 1). Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC104186, AK313322
    Consensus CDS
    CCDS2691.1
    UniProtKB/Swiss-Prot
    B2R8D0, G5E9N0, O60495, O75355, Q8N6K2
    UniProtKB/TrEMBL
    A0ACI8QTZ0
    Related
    ENSP00000401565.1, ENST00000456402.5
    Conserved Domains (1) summary
    cl17037
    Location:56 → 478
    NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily

  3. NM_001291961.2 → NP_001278890.1  ectonucleoside triphosphate diphosphohydrolase 3 isoform 2

    See identical proteins and their annotated locations for NP_001278890.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and includes a different terminal 3' exon compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC104186, BC029869
    Consensus CDS
    CCDS74919.1
    UniProtKB/TrEMBL
    A0ACI8QTZ0
    Related
    ENSP00000702204.1, ENST00001032387.1
    Conserved Domains (1) summary
    cl17037
    Location:56 → 448
    NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    40387184..40428744
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011534266.4 → XP_011532568.1  ectonucleoside triphosphate diphosphohydrolase 3 isoform X1

    Related
    ENSP00000792292.1, ENST00001122487.1
    Conserved Domains (1) summary
    cl17037
    Location:56 → 281
    NBD_sugar-kinase_HSP70_actin; Nucleotide-Binding Domain of the sugar kinase/HSP70/actin superfamily

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    40402253..40443812
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054348477.1 → XP_054204452.1  ectonucleoside triphosphate diphosphohydrolase 3 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O75355.2 GenPept UniProtKB/Swiss-Prot:O75355

Gene LinkOut

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