PPM1D
Chr 17ADprotein phosphatase, Mg2+/Mn2+ dependent 1D
Also known as: IDDGIP, JDVS, PP2C-DELTA, WIP1
This Ser/Thr protein phosphatase negatively regulates the p53 stress response pathway by dephosphorylating p53, CHEK1, and p38 MAP kinase, thereby controlling cell cycle checkpoints and apoptosis. Mutations cause Jansen-de Vries syndrome, a neurodevelopmental disorder, through autosomal dominant inheritance. The gene is extremely intolerant to loss-of-function variants (pLI ~0), indicating that complete loss of protein function is likely incompatible with normal development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is gain-of-function.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PPM1D · 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
External Resources
Links to major genomics databases and tools