PPP2R3B

Chr Y

protein phosphatase 2 regulatory subunit B''beta

Also known as: NYREN8, PPP2R3L, PPP2R3LY, PR48, PR70

The protein functions as a regulatory subunit of protein phosphatase 2A, modulating the enzyme's substrate selectivity, catalytic activity, and subcellular localization to control cell growth and division through serine/threonine dephosphorylation. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. This gene is highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.89
Clinical SummaryPPP2R3B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 1.99
OE 0.59 (0.400.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.40Z-score
OE missense 1.22 (1.121.32)
407 obs / 334.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.59 (0.400.89)
00.351.4
Missense OE1.22 (1.121.32)
00.61.4
Synonymous OE1.42
01.21.6
LoF obs/exp: 16 / 27.2Missense obs/exp: 407 / 334.7Syn Z: -4.15
DN
0.7035th %ile
GOF
0.77top 25%
LOF
0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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

PPP2R3B · 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