PPP6C

Chr 9

protein phosphatase 6 catalytic subunit

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.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
LOFmechanismLOEUF 0.40
Clinical SummaryPPP6C
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.855
Z-score 3.47
OE 0.15 (0.070.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.58Z-score
OE missense 0.48 (0.400.57)
93 obs / 194.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.070.40)
00.351.4
Missense OE0.48 (0.400.57)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 3 / 19.5Missense obs/exp: 93 / 194.3Syn Z: -0.57
DN
0.3892th %ile
GOF
0.4184th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.40

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

PPP6C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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