PPP4R2

Chr 3

protein phosphatase 4 regulatory subunit 2

Also known as: PP4R2

NCBI Gene: 151987ENSG00000163605UniProt: Q9NY27

The protein encoded by PPP4R2 is a regulatory subunit of serine/threonine-protein phosphatase 4 that is essential for DNA double strand break repair, centrosomal microtubule organization, and spliceosomal snRNP processing. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. This gene is highly constrained against loss-of-function variants in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
12
P/LP submissions
0%
P/LP missense
0.16
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— PPP4R2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 99 VUS of 134 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 0.998
Z-score 4.00
OE 0.00 (0.00–0.16)
Highly constrained

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

Missense Constraint
0.00Z-score
OE missense 1.00 (0.89–1.12)
206 obs / 206.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.16)
0≤0.351.4
Missense OE1.00 (0.89–1.12)
0≤0.61.4
Synonymous OE1.27
0≤1.21.6
LoF obs/exp: 0 / 18.7Missense obs/exp: 206 / 206.0Syn Z: -1.81
DN
0.2599th %ile
GOF
0.2497th %ile
LOF
0.75top 10%

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

LOFprediction above median · LOEUF 0.16

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

134 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic2
VUS99
Likely Benign4
10
Pathogenic
2
Likely Pathogenic
99
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
2
0
2
VUS
0
96
3
0
99
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total0100150115

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

View in ClinVar →

Protein Context — Lollipop Plot

PPP4R2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients