ENPP2

Chr 8

ectonucleotide pyrophosphatase/phosphodiesterase 2

Also known as: ATX, ATX-X, AUTOTAXIN, LysoPLD, NPP2, PD-IALPHA, PDNP2

NCBI Gene: 5168 ENSG00000136960 UniProt: Q13822

This gene encodes a secreted lysophospholipase D that hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA), a signaling molecule involved in cell proliferation, migration, and angiogenesis. Biallelic mutations cause generalized arterial calcification of infancy (GACI), a severe autosomal recessive disorder presenting in early infancy with calcification of large arteries and cardiac complications. The gene shows high tolerance to loss-of-function variants (low pLI score), consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and a phospholipase, which catalyzes production of lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and chemotaxis. This gene product stimulates the motility of tumor cells and has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The gene product is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.43

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429