PPP4R1
Chr 18protein phosphatase 4 regulatory subunit 1
Also known as: MEG1, PP4(Rmeg), PP4R1
This protein serves as a regulatory subunit of serine/threonine-protein phosphatase 4 (PP4) and regulates HDAC3 dephosphorylation and TNF-induced NF-kappa-B signaling pathways. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.24), indicating intolerance to protein-disrupting mutations.
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
261 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 | 97 | 0 | 97 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 123 | 12 | 0 | 135 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 125 | 111 | 0 | 236 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PPP4R1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools