PLPP3
Chr 1phospholipid phosphatase 3
Also known as: Dri42, LPP3, PAP2B, PPAP2B, VCIP
The protein functions as a plasma membrane phospholipid phosphatase that dephosphorylates various bioactive lipid mediators including lysophosphatidic acid and sphingosine 1-phosphate, regulating vascular homeostasis and cerebellar development. Mutations cause autosomal recessive hypomyelinating leukodystrophy with ataxia and intellectual disability, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating it is essential for normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PLPP3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools