ENPP2
Chr 8ectonucleotide pyrophosphatase/phosphodiesterase 2
Also known as: ATX, ATX-X, AUTOTAXIN, LysoPLD, NPP2, PD-IALPHA, PDNP2
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
225 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 55 | 0 | 55 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 120 | 10 | 1 | 131 |
Likely Benign | 0 | 3 | 0 | 2 | 5 |
Benign | 0 | 2 | 2 | 1 | 5 |
| Total | 0 | 125 | 67 | 4 | 196 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ENPP2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
RELIEF: Multimodal Prehabilitation to Treat Fatigue in Patients With Primary Biliary Cholangitis
RECRUITINGElectroacupuncture Therapy in Reducing Chronic Pain in Patients After Breast Cancer Treatment
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools