PPP2R2B

Chr 5AD

protein phosphatase 2 regulatory subunit Bbeta

Also known as: B55BETA, PP2AB55BETA, PP2ABBETA, PP2APR55B, PP2APR55BETA, PR2AB55BETA, PR2ABBETA, PR2APR55BETA

PPP2R2B encodes a regulatory subunit of protein phosphatase 2A that modulates substrate selectivity and catalytic activity of this major serine/threonine phosphatase involved in cell growth control. Mutations cause spinocerebellar ataxia 12 (SCA12), characterized by progressive degeneration of the cerebellum and sometimes brainstem and spinal cord, resulting in poor coordination of speech and body movements. SCA12 follows autosomal dominant inheritance and is caused by CAG repeat expansions in the 5' untranslated region of the gene.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.291 OMIM phenotype
Clinical SummaryPPP2R2B
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.985
Z-score 3.90
OE 0.09 (0.040.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.25Z-score
OE missense 0.62 (0.540.70)
167 obs / 271.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.040.29)
00.351.4
Missense OE0.62 (0.540.70)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 2 / 21.5Missense obs/exp: 167 / 271.0Syn Z: 0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPPP2R2B-related neurodevelopmental disorderLOFAD
DN
0.4587th %ile
GOF
0.3293th %ile
LOF
0.76top 10%

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

LOFprediction above median · LOEUF 0.29

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

PPP2R2B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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