PPP3R2

Chr 9

protein phosphatase 3 regulatory subunit B, beta

The protein functions as a regulatory subunit of calcineurin, a calcium-dependent protein phosphatase that confers calcium sensitivity to the enzyme complex. Mutations in PPP3R2 cause disease through a dominant-negative mechanism, though specific associated neurological phenotypes are not established in the provided data. The low pLI score suggests the gene is tolerant to loss-of-function variants.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.89
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryPPP3R2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.001
Z-score -0.31
OE 1.18 (0.551.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.00Z-score
OE missense 1.00 (0.851.17)
108 obs / 108.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.18 (0.551.89)
00.351.4
Missense OE1.00 (0.851.17)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 4 / 3.4Missense obs/exp: 108 / 108.0Syn Z: 0.99
DN
0.81top 10%
GOF
0.76top 25%
LOF
0.2485th %ile

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

DNprediction above median
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

PPP3R2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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