ENTPD1 (CD39): Ectonucleoside Triphosphate Diphosphohydrolase 1
A key immunoregulatory ectoenzyme hydrolyzing ATP/ADP to AMP, implicated in cancer immunity, thrombosis, and inflammatory diseases.
Gene Information Card
| Symbol | ENTPD1 |
|---|---|
| Full Name | Ectonucleoside triphosphate diphosphohydrolase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q24.1 |
| NCBI Gene ID | 953 ncbi.nlm.nih.gov/gene/953 |
| Ensembl ID | ENSG00000138185 |
| UniProt ID | P49961 |
| OMIM ID | 601752 |
| HGNC ID | 3363 |
| Aliases | CD39, ATPDase, NTPDase-1, SPG64 |
Description
The ENTPD1 gene encodes CD39, a cell-surface enzyme that hydrolyzes extracellular ATP and ADP to AMP, thereby modulating purinergic signaling. It is expressed on immune cells (e.g., regulatory T cells, endothelial cells) and plays a critical role in immunosuppression, inflammation, and hemostasis. Dysregulation of ENTPD1 is associated with cancer progression, autoimmune diseases, and thrombotic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | ENTPD1 overexpression in tumor microenvironment degrades ATP, reducing pro-inflammatory signaling and promoting immune evasion. | COSMIC, literature |
| Thrombotic disorders | Altered ENTPD1 activity affects platelet aggregation and vascular homeostasis. | OMIM, literature |
| Inflammatory bowel disease (IBD) | Reduced ENTPD1 activity may exacerbate intestinal inflammation via increased ATP. | ClinVar, literature |
| Autoimmune diseases (e.g., lupus) | Dysregulated CD39 expression on regulatory T cells impairs immunosuppression. | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | High | High expression in immune tissues |
| Spleen | High | High expression in immune tissues |
| Lung | Medium | Moderate expression |
| Liver | Low | Low expression |
| Brain | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Regulatory T cells (Tregs) | High | Key immunosuppressive function |
| Endothelial cells | High | Vascular homeostasis |
| Natural killer (NK) cells | Medium | Moderate expression |
| HEK293 | Low | Low endogenous expression |
| HeLa | Low | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.953A>G (p.Gln318Arg) | Missense | Rare | Potential effect on enzyme activity (reported in ClinVar) |
| c.1079C>T (p.Thr360Met) | Missense | Rare | Uncertain significance |
| c.1291G>A (p.Val431Ile) | Missense | Rare | Uncertain significance |
| c.1477C>T (p.Arg493Trp) | Missense | Rare | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ENTPD1 are rare; they may reduce ATP hydrolysis, leading to increased extracellular ATP and pro-inflammatory responses.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; overexpression (not mutation) is more common in cancer.
Dominant Negative (DN)
No dominant-negative mutations have been reported for ENTPD1.
View complete mutation data：
Gene Ontology (GO)
| • hydrolase activity | • ATP diphosphatase activity |
| • metal ion binding | • plasma membrane |
| • extracellular region | • immune response |
| • purine nucleotide catabolic process |
Pathways
• Purinergic signaling
• Adenosine pathway (ATP → ADP → AMP → Adenosine)
• Regulation of immune response
Protein Summary
CD39 is a 510-amino acid type II transmembrane glycoprotein with two transmembrane domains and a large extracellular loop containing the catalytic site. It exists as a homotetramer and requires calcium or magnesium for activity. CD39 hydrolyzes ATP and ADP to AMP, which is further converted to adenosine by CD73. This pathway suppresses immune responses by activating adenosine receptors on immune cells. CD39 is a target for cancer immunotherapy (e.g., antibodies blocking its activity).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ENTPD1 Knockout HEK293 Cell Line | EDJ-KQ17780 | Human | 953 | Details Get a Quote |
| ENTPD1 Knockout A-549 Cell Line | EDJ-KQ19857 | Human | 953 | Details Get a Quote |
| ENTPD1 Knockout HCT 116 Cell Line | EDJ-KQ19859 | Human | 953 | Details Get a Quote |
| ENTPD1 Knockout HeLa Cell Line | EDJ-KQ19860 | Human | 953 | Details Get a Quote |
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