PPP2R3A

Chr 3

protein phosphatase 2 regulatory subunit B''alpha

Also known as: PPP2R3, PR130, PR72

This gene encodes one of the regulatory subunits of the protein phosphatase 2. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Jun 2010]

OMIMResearchGenerating clinical summary…
GOFmechanismLOEUF 0.36
Clinical SummaryPPP2R3A
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
162 VUS of 217 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.36LOEUF
pLI 0.623
Z-score 5.00
OE 0.21 (0.130.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
-0.04Z-score
OE missense 1.00 (0.941.07)
591 obs / 588.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.21 (0.130.36)
00.351.4
Missense OE?1.00 (0.941.07)
00.61.4
Synonymous OE?1.01
01.21.6
LoF obs/exp: 10 / 47.0Missense obs/exp: 591 / 588.3Syn Z: -0.15

This gene — mechanism propensity

DN
0.5673th %ile
GOF
0.6834th %ile
LOF
0.53top 25%

The highest-scoring mechanism for this gene is gain-of-function.

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

217 submitted variants in ClinVar

Classification Summary

VUS162
Likely Benign21
Benign23
162
VUS
21
Likely Benign
23
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
161
0
0
162
Likely Benign
0
11
2
8
21
Benign
2
12
2
7
23
Total3184415206

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap PPP2R3A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

PPP2R3A · 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.

Search ClinicalTrials.gov →