PPP6R2

Chr 22

protein phosphatase 6 regulatory subunit 2

Also known as: KIAA0685, PP6R2, SAP190, SAPS2

The protein serves as a regulatory subunit of protein phosphatase 6, functioning as a scaffolding component and mediating dephosphorylation of targets including the T-loop of Aurora A kinase, which is essential for proper spindle formation and chromosome alignment during mitosis. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, affecting neurological development and seizure control in early childhood. This gene shows significant constraint against loss-of-function variants (LOEUF 0.411), indicating that such mutations are typically not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.41
Clinical SummaryPPP6R2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.164
Z-score 4.51
OE 0.24 (0.150.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.93Z-score
OE missense 0.89 (0.830.96)
514 obs / 577.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.150.41)
00.351.4
Missense OE0.89 (0.830.96)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 10 / 41.3Missense obs/exp: 514 / 577.2Syn Z: -0.53
DN
0.5771th %ile
GOF
0.6930th %ile
LOF
0.4135th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PPP6R2 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found