PPP2R2C

Chr 4

protein phosphatase 2 regulatory subunit Bgamma

Also known as: B55-GAMMA, B55gamma, IMYPNO, IMYPNO1, PR52, PR55G

The protein is a regulatory subunit of protein phosphatase 2A that modulates substrate selectivity and catalytic activity of this major serine/threonine phosphatase involved in controlling cell growth and division. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
86
P/LP submissions
0%
P/LP missense
0.38
LOEUF
LOF
Mechanism· predicted
Clinical SummaryPPP2R2C
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.90) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
86 unique Pathogenic / Likely Pathogenic· 47 VUS of 147 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.38LOEUF
pLI 0.900
Z-score 3.60
OE 0.15 (0.070.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.53Z-score
OE missense 0.42 (0.360.49)
123 obs / 293.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.15 (0.070.38)
00.351.4
Missense OE0.42 (0.360.49)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 3 / 20.6Missense obs/exp: 123 / 293.2Syn Z: -0.62
DN
0.5378th %ile
GOF
0.4085th %ile
LOF
0.67top 25%

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

147 submitted variants in ClinVar

Classification Summary

Pathogenic81
Likely Pathogenic5
VUS47
Benign2
81
Pathogenic
5
Likely Pathogenic
47
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
81
0
81
Likely Pathogenic
0
0
5
0
5
VUS
0
38
9
0
47
Likely Benign
0
0
0
0
0
Benign
0
0
1
1
2
Total038961135

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

View in ClinVar →

Protein Context — Lollipop Plot

PPP2R2C · 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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Clinical Literature
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