ENPP4: Ectonucleotide Pyrophosphatase/Phosphodiesterase 4
A comprehensive biomedical resource for ENPP4 gene, including genomic annotation, expression, mutations, and disease associations.
Gene Information Card
| Symbol | ENPP4 |
|---|---|
| Full Name | Ectonucleotide Pyrophosphatase/Phosphodiesterase 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 6p21.1 |
| NCBI Gene ID | 22875 ncbi.nlm.nih.gov/gene/22875 |
| Ensembl ID | ENSG00000112658 |
| UniProt ID | Q9Y6X5 |
| OMIM ID | 606773 |
| HGNC ID | 3359 |
| Aliases | NPP4, ENPP-4, GP-4, GP4 |
Description
ENPP4 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 4) encodes a member of the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a transmembrane glycoprotein that hydrolyzes extracellular nucleotides, producing nucleoside monophosphates and inorganic pyrophosphate. It plays a role in purinergic signaling, nucleotide metabolism, and may be involved in cancer progression and immune modulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | ENPP4 overexpression may promote tumor cell proliferation and migration through modulation of extracellular nucleotide levels. | COSMIC; PMID: 25691885 |
| Colorectal cancer | Altered ENPP4 expression associated with poor prognosis; potential role in nucleotide scavenging. | COSMIC; PMID: 27864382 |
| Ovarian cancer | ENPP4 upregulation linked to chemoresistance and altered purinergic signaling. | COSMIC; PMID: 29367608 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 9.8 | Medium |
| Lung | 7.2 | Low |
| Breast | 6.1 | Low |
| Colon | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 8.3 | Moderate expression |
| HCT116 (colorectal cancer) | 7.1 | Moderate expression |
| A549 (lung cancer) | 6.5 | Low expression |
| HEK293 (embryonic kidney) | 10.2 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.01% | Unknown functional impact; reported in COSMIC |
| c.1246G>A (p.Gly416Arg) | Missense | <0.01% | Reported in COSMIC; no known disease association |
| c.1573_1574insA | Frameshift | <0.01% | Predicted loss-of-function; rare |
Mutation functional classification
Loss of Function (LOF)
Frameshift insertion c.1573_1574insA likely leads to truncated protein and loss of enzymatic activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in ENPP4.
Dominant Negative (DN)
No evidence for dominant-negative effects in ENPP4.
View complete mutation data：
Gene Ontology (GO)
| • nucleotide diphosphatase activity (GO:0004551) | • ATP binding (GO:0005524) |
| • integral component of membrane (GO:0016021) | • cAMP biosynthetic process (GO:0006171) |
| • platelet activation (GO:0030168) | • signal transduction (GO:0007165) |
Pathways
• Purinergic signaling (Reactome: R-HSA-418594)
• Extracellular nucleotide metabolism (KEGG: hsa00230)
• cGMP-PKG signaling pathway (KEGG: hsa04022)
Protein Summary
ENPP4 is a transmembrane protein with ectonucleotide pyrophosphatase/phosphodiesterase activity. It hydrolyzes extracellular nucleotides such as ATP and ADP to AMP and inorganic pyrophosphate, regulating purinergic signaling. The protein is expressed in various tissues, with highest levels in liver and kidney. It has been implicated in cancer biology, particularly in breast, colorectal, and ovarian cancers, where altered expression may influence tumor progression and chemoresistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ENPP4 Knockout HEK293 Cell Line | EDJ-KQ7710 | Human | 22875 | Details Get a Quote |
| ENPP4 Knockout A-549 Cell Line | EDJ-KQ33104 | Human | 22875 | Details Get a Quote |
| ENPP4 Knockout HCT 116 Cell Line | EDJ-KQ33105 | Human | 22875 | Details Get a Quote |
| ENPP4 Knockout HeLa Cell Line | EDJ-KQ55648 | Human | 22875 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
