MPPE1
Chr 18metallophosphoesterase 1
Also known as: Cdc1, PGAP5
The protein is a metallophosphoesterase that removes ethanolamine-phosphate from GPI-anchor protein intermediates during glycan remodeling, enabling efficient transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi apparatus. Mutations in MPPE1 cause congenital disorder of glycosylation type Iq, which presents with intellectual disability, seizures, and hypotonia with autosomal recessive inheritance. The gene shows relaxed evolutionary constraint with a high LOEUF score of 1.207, indicating tolerance to loss-of-function variants in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
194 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 | 89 | 0 | 89 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 68 | 15 | 0 | 83 |
Likely Benign | 0 | 6 | 0 | 0 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 74 | 106 | 0 | 180 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MPPE1 · 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
External Resources
Links to major genomics databases and tools