PPP1R15B

Chr 1

protein phosphatase 1 regulatory subunit 15B

Also known as: CREP, MSSGM2

This gene encodes a protein phosphatase I-interacting protein that promotes the dephosphorylation of eukaryotic translation initiation factor 2A to regulate translation under conditions of cellular stress. The transcribed messenger RNA contains two upstream open reading frames (ORFs) that repress translation of the main protein coding ORF under normal conditions, while the protein coding ORF is expressed at high levels in response to stress. Continual translation of the mRNA under conditions of eukaryotic translation initiation factor 2A inactivation is thought to create a feedback loop for reactivation of the gene during recovery from stress. In addition, it has been shown that this protein plays a role in membrane traffic that is independent of translation and that it is required for exocytosis from erythroleukemia cells. Allelic variants of this gene are associated with microcephaly, short stature, and impaired glucose metabolism. [provided by RefSeq, Feb 2016]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.51
Clinical SummaryPPP1R15B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.51LOEUF
pLI 0.151
Z-score 3.33
OE 0.26 (0.140.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
-1.35Z-score
OE missense 1.20 (1.111.30)
431 obs / 359.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.26 (0.140.51)
00.351.4
Missense OE?1.20 (1.111.30)
00.61.4
Synonymous OE?1.08
01.21.6
LoF obs/exp: 6 / 23.4Missense obs/exp: 431 / 359.1Syn Z: -0.79
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPPP1R15B-related severe microcephaly, short stature, and intellectual disabilityLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6261th %ile
GOF
0.6346th %ile
LOF
0.4038th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PPP1R15B · 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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