PLPP6
Chr 9phospholipid phosphatase 6
Also known as: LPRP-B, PA-PSP, PDP1, PPAPDC2, PSDP, bA6J24.6
The protein is a magnesium-independent polyisoprenoid diphosphatase that catalyzes dephosphorylation of presqualene, farnesyl, geranyl and geranylgeranyl diphosphates, functioning in cholesterol biosynthesis, protein prenylation, and innate immune response through neutrophil activation regulation. PLPP6 mutations cause autosomal recessive hypomyelinating leukodystrophy-15, a severe early-onset disorder affecting white matter development in the central nervous system. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-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.
ClinVar Variant Classifications
200 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 | 112 | 0 | 112 |
Likely Pathogenic | 0 | 0 | 7 | 0 | 7 |
VUS | 0 | 54 | 15 | 0 | 69 |
Likely Benign | 0 | 3 | 0 | 2 | 5 |
Benign | 0 | 3 | 3 | 0 | 6 |
| Total | 0 | 60 | 137 | 2 | 199 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PLPP6 · 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 →No open access results found
External Resources
Links to major genomics databases and tools