PPP4R2

Chr 3

protein phosphatase 4 regulatory subunit 2

Also known as: PP4R2

NCBI Gene: 151987 ENSG00000163605 UniProt: Q9NY27 OMIM: 613822

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.16

Clinical Summary— PPP4R2

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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.

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ClinVar Variants

100 VUS of 123 total submissions

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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 OE?0.00 (0.00–0.16)

0≤0.351.4

Missense OE?1.00 (0.89–1.12)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 0 / 18.7Missense obs/exp: 206 / 206.0Syn Z: -1.81

This gene — mechanism propensity

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

123 submitted variants in ClinVar

ClinVar

Classification Summary

VUS100

Likely Benign4

100

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	100	100
Likely Benign	4	4
Benign	0	0
Total	104	104

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap PPP4R2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →