PPP6C
Chr 9protein phosphatase 6 catalytic subunit
Also known as: PP6, PP6C
The protein serves as the catalytic subunit of protein phosphatase 6, which dephosphorylates key regulatory proteins to control cell cycle progression, spindle positioning during mitosis, and innate immune signaling pathways including MAP3K7, RIG-I, and cGAS-STING. Loss-of-function mutations in PPP6C cause autosomal dominant intellectual disability, developmental delay, and seizures. The high constraint scores (pLI 0.86, LOEUF 0.40) indicate this gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% 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
69 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 | 26 | 0 | 26 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 18 | 1 | 0 | 19 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 19 | 28 | 1 | 48 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PPP6C · 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