ENPP3: Ectonucleotide Pyrophosphatase/Phosphodiesterase 3
A key regulator of nucleotide metabolism and signaling, implicated in cancer, immune modulation, and metabolic disorders.
Gene Information Card
| Symbol | ENPP3 |
|---|---|
| Full Name | Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q23.2 |
| NCBI Gene ID | 5167 ncbi.nlm.nih.gov/gene/5167 |
| Ensembl ID | ENSG00000112210 |
| UniProt ID | O14638 |
| OMIM ID | 606179 |
| HGNC ID | 3358 |
| Aliases | CD203c, PDNP3, NPP3, gp130RB13-6 |
Description
ENPP3 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 3) encodes a type II transmembrane glycoprotein that hydrolyzes extracellular nucleotides, such as ATP and ADP, to AMP and inorganic pyrophosphate. It is also known as CD203c and is expressed on activated basophils and mast cells, playing a role in allergic inflammation. The protein is involved in purinergic signaling, bone mineralization, and cell migration. ENPP3 is upregulated in various cancers and is a potential biomarker and therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Basophil activation / Allergy | ENPP3 (CD203c) is upregulated on basophils upon IgE-mediated activation; used as a diagnostic marker for allergen sensitivity. | ClinVar, NCBI Gene, literature |
| Ovarian cancer | Overexpression of ENPP3 in ovarian cancer cells promotes tumor growth and metastasis via modulation of extracellular nucleotide levels. | COSMIC, NCBI Gene |
| Glioma | ENPP3 expression is elevated in glioblastoma and correlates with poor prognosis; involved in cell proliferation and migration. | COSMIC, literature |
| Colorectal cancer | ENPP3 is upregulated in colorectal cancer tissues and associated with advanced stage and metastasis. | COSMIC, NCBI Gene |
| Hypophosphatasia | Mutations in ENPP3 can lead to altered pyrophosphate metabolism, contributing to defective bone mineralization. | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 8.3 | Low |
| Lung | 6.7 | Low |
| Spleen | 4.2 | Low |
| Bone marrow | 3.1 | Low |
| Brain | 1.8 | Not detected |
| Heart | 2.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in kidney-derived line |
| HeLa | 8.9 | Moderate expression |
| A549 | 6.4 | Low expression |
| K562 | 3.1 | Low expression |
| MCF7 | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1048C>T (p.Arg350Trp) | Missense | Rare | Loss of catalytic activity; associated with hypophosphatasia-like phenotype |
| c.1573G>A (p.Glu525Lys) | Missense | Rare | Reduced enzyme activity; reported in ClinVar |
| c.1990C>T (p.Arg664Cys) | Missense | Rare | Unknown functional effect; observed in cancer samples |
| c.2245_2247del (p.Val749del) | In-frame deletion | Rare | Altered protein stability; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg350Trp) reduce or abolish nucleotide pyrophosphatase activity, impairing extracellular nucleotide hydrolysis and pyrophosphate homeostasis.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in ENPP3.
Dominant Negative (DN)
No dominant-negative mutations described for ENPP3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Purinergic signaling (Reactome: R-HSA-418594)
• Extracellular nucleotide metabolism (Reactome: R-HSA-418596)
• Pyrophosphate metabolism (Reactome: R-HSA-1483248)
• cAMP signaling pathway (KEGG: hsa04024)
• Calcium signaling pathway (KEGG: hsa04020)
Protein Summary
ENPP3 is a 875-amino acid type II transmembrane glycoprotein with an extracellular domain containing a catalytic site that hydrolyzes ATP, ADP, and other nucleotides to AMP and pyrophosphate. It exists as a homodimer and is anchored to the plasma membrane via a single transmembrane helix. The protein is heavily glycosylated and contains a somatomedin-B-like domain and a nuclease-like domain. ENPP3 is expressed on activated basophils (as CD203c) and in various tissues, with highest levels in kidney and liver. It regulates purinergic signaling, cell adhesion, and migration. In cancer, ENPP3 overexpression promotes tumor progression and is associated with poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ENPP3 Knockout HEK293 Cell Line | EDJ-KQ17752 | Human | 5169 | Details Get a Quote |
| ENPP3 Knockout HeLa Cell Line | EDJ-KQ54112 | Human | 5169 | Details Get a Quote |
| ENPP3 Knockout A-549 Cell Line | EDJ-KQ62600 | Human | 5169 | Details Get a Quote |
| ENPP3 Knockout HCT 116 Cell Line | EDJ-KQ71073 | Human | 5169 | Details Get a Quote |
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