PPP2R2D

Chr 10

protein phosphatase 2 regulatory subunit Bdelta

Also known as: B55D, B55delta, MDS026

The PPP2R2D protein functions as a substrate-recognition subunit of protein phosphatase 2A (PP2A), controlling mitosis entry and exit and mediating chromosome clustering during late mitosis through dephosphorylation of target proteins. Mutations cause autosomal dominant developmental and epileptic encephalopathy with early infantile onset, featuring intellectual disability, seizures, and developmental delays. This gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.38), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.38
Clinical SummaryPPP2R2D
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.917
Z-score 3.35
OE 0.12 (0.050.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.14Z-score
OE missense 0.62 (0.540.71)
155 obs / 250.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.12 (0.050.38)
00.351.4
Missense OE0.62 (0.540.71)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 2 / 16.8Missense obs/exp: 155 / 250.5Syn Z: -0.32
DN
0.4884th %ile
GOF
0.3986th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.38

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

PPP2R2D · 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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