PPP2R2D

Chr 10

protein phosphatase 2 regulatory subunit Bdelta

Also known as: B55D, B55delta, MDS026

NCBI Gene: 55844 ENSG00000175470 UniProt: Q66LE6 OMIM: 613992

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable enzyme-substrate adaptor activity and protein phosphatase regulator activity. Predicted to be involved in exit from mitosis and regulation of chromosome segregation. Predicted to be located in cytoplasm. Predicted to be part of protein phosphatase type 2A complex. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.38

Clinical Summary— PPP2R2D

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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.

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ClinVar Variants

9 VUS of 14 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.917

Z-score 3.35

OE 0.12 (0.05–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.14Z-score

OE missense 0.62 (0.54–0.71)

155 obs / 250.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.38)

0≤0.351.4

Missense OE?0.62 (0.54–0.71)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 2 / 16.8Missense obs/exp: 155 / 250.5Syn Z: -0.32

This gene — mechanism propensity

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

14 submitted variants in ClinVar

ClinVar

Classification Summary

VUS9

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	9	9
Likely Benign	0	0
Benign	0	0
Total	9	9

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

97 pathogenic / likely-pathogenic (of 117) ClinVar copy-number / structural variants overlap PPP2R2D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →