PPP1R2

Chr 3

protein phosphatase 1 regulatory inhibitor subunit 2

Also known as: IPP-2, IPP2, PPP1R2A

NCBI Gene: 5504 ENSG00000184203 UniProt: P41236

Protein phosphatase-1 (PP1) is one of the main eukaryotic serine/threonine phosphatases. The protein encoded by this gene binds to the catalytic subunit of PP1, strongly inhibiting its activity. Ten related pseudogenes have been found throughout the human genome. Several splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

Research

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.75

Clinical Summary— PPP1R2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

19 VUS of 30 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.75LOEUF

pLI 0.069

Z-score 2.19

OE 0.33 (0.16–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.68Z-score

OE missense 0.82 (0.69–0.97)

89 obs / 109.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.16–0.75)

0≤0.351.4

Missense OE?0.82 (0.69–0.97)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 4 / 12.3Missense obs/exp: 89 / 109.1Syn Z: 0.26

This gene — mechanism propensity

0.81top 10%

GOF

0.5367th %ile

LOF

0.2678th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

30 submitted variants in ClinVar

ClinVar

Classification Summary

VUS19

Likely Benign4

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	19	19
Likely Benign	4	4
Benign	0	0
Total	23	23

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap PPP1R2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →