PPM1A
Chr 14protein phosphatase, Mg2+/Mn2+ dependent 1A
Also known as: PP2C-ALPHA, PP2CA, PP2Calpha
PPM1A encodes a serine/threonine protein phosphatase that negatively regulates multiple cellular signaling pathways including TGF-beta, NF-kappa-B, and AMPK signaling through dephosphorylation of key regulatory proteins. Mutations cause autosomal dominant intellectual disability with developmental delay, and the gene is highly intolerant to loss-of-function variants. The phenotype typically manifests in early childhood with cognitive impairment as the primary feature.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
PPM1A · 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