ENPP2 (Autotaxin): A Key Regulator of Lipid Signaling and Its Role in Cancer, Fibrosis, and Inflammation
Explore the ENPP2 gene, its protein product autotaxin, and its implications in disease, with curated data from authoritative genomic databases.
Gene Information Card
| Symbol | ENPP2 |
|---|---|
| Full Name | Ectonucleotide pyrophosphatase/phosphodiesterase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.12 |
| NCBI Gene ID | 5168 ncbi.nlm.nih.gov/gene/5168 |
| Ensembl ID | ENSG00000136960 |
| UniProt ID | Q13822 |
| OMIM ID | 601065 |
| HGNC ID | 3357 |
| Aliases | ATX, ATX-X, PDNP2, LysoPLD, NPP2 |
Description
The ENPP2 gene encodes autotaxin (ATX), a secreted glycoprotein that functions as a lysophospholipase D. It catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a potent lipid mediator involved in cell proliferation, migration, and survival. Autotaxin is widely expressed and plays critical roles in embryonic development, vascular formation, and neural development. Dysregulation of ENPP2/ATX is implicated in various cancers, fibrotic diseases, and inflammatory conditions, making it a promising therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of ENPP2 leads to increased LPA production, promoting tumor cell proliferation, invasion, and angiogenesis. | COSMIC; PubMed studies (e.g., Liu et al., 2009; Houben et al., 2018) |
| Pulmonary fibrosis | Elevated ATX activity in lung tissue enhances LPA signaling, driving fibroblast recruitment and fibrosis. | ClinVar; PubMed (Tager et al., 2008) |
| Rheumatoid arthritis | Increased ATX expression in synovial fluid contributes to inflammatory joint destruction via LPA-mediated cytokine release. | PubMed (Nikitopoulou et al., 2012) |
| Neuropathic pain | ATX-LPA signaling is involved in nerve injury-induced pain hypersensitivity. | PubMed (Inoue et al., 2008) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | High | High |
| Lung | Moderate | Medium |
| Liver | Moderate | Medium |
| Brain | Low | Low |
| Kidney | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cancer cell line |
| A549 | Moderate | Lung carcinoma |
| MCF7 | Low | Breast cancer |
| HUVEC | Moderate | Endothelial cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.875C>T (p.Thr292Ile) | Missense | Rare | Potential effect on enzyme activity; not well characterized |
| c.1246G>A (p.Val416Met) | Missense | Rare | Unknown significance |
| c.1678C>T (p.Arg560Cys) | Missense | Rare | Reported in cancer samples; functional impact unclear |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ENPP2 are rare and not well documented; complete knockout is embryonic lethal in mice, indicating essentiality.
Gain of Function (GOF)
Gain-of-function mutations are not commonly reported; however, overexpression or increased enzymatic activity is observed in cancers and fibrosis.
Dominant Negative (DN)
No dominant-negative mutations have been described for ENPP2.
View complete mutation data：
Gene Ontology (GO)
| • lysophospholipase D activity | • phosphodiesterase I activity |
| • nucleotide diphosphatase activity | • extracellular region |
| • plasma membrane | • lipid metabolic process |
| • cell migration | • angiogenesis |
Pathways
• Lysophosphatidic acid (LPA) signaling
• Glycerophospholipid metabolism
• Sphingolipid metabolism
Protein Summary
Autotaxin (ATX) is a secreted enzyme of the ectonucleotide pyrophosphatase/phosphodiesterase family. It contains two somatomedin-B-like domains, a phosphodiesterase domain, and a nuclease-like domain. ATX is the major producer of extracellular LPA, which signals through six G-protein-coupled receptors (LPAR1-6) to regulate diverse cellular processes. Its expression is tightly regulated, and its dysregulation contributes to disease pathogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ENPP2 Knockout HEK293 Cell Line | EDJ-KQ13290 | Human | 5168 | Details Get a Quote |
| ENPP2 Knockout U-2932 Cell Line | EDJ-KZ216 | Human | 5168 | Details Get a Quote |
| ENPP2 Knockout HeLa Cell Line | EDJ-KQ54111 | Human | 5168 | Details Get a Quote |
| ENPP2 Knockout A-549 Cell Line | EDJ-KQ62599 | Human | 5168 | Details Get a Quote |
| ENPP2 Knockout HCT 116 Cell Line | EDJ-KQ71072 | Human | 5168 | Details Get a Quote |
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