ArticleDiabetes2015
A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Clinical and Molecular Heterogeneity Underlying Monogenic Causes of Pediatric Diabetes Associated to Brain Developmental Disorders.Clinical genetics · 2025Pooled it
- PPP1R21-Related neurodevelopmental disorder: Phenotypic delineation, variant spectrum, and pathophysiological mechanisms.Neurogenetics · 2026Review
- JNK and p53 cause human and mouse β cell death during excessive unfolded protein response.The Journal of clinical investigation · 2026Article
- Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Evaluating regional heritability mapping methods for identifying QTLs in a wild population of Soay sheep.Heredity · 2025Article
- Article
- Neonatal and Syndromic Forms of Diabetes.Current diabetes reports · 2025Review
- Mapping the Genetic Architecture of the Adaptive Integrated Stress Response inbioRxiv : the preprint server for biology · 2024Article
- Article
- Functional validation of EIF2AK4 (GCN2) missense variants associated with pulmonary arterial hypertension.Human molecular genetics · 2024Article
- Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma.Nature communications · 2024Article
- The ISR downstream target ATF4 represses long-term memory in a cell type-specific manner.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A helical fulcrum in eIF2B coordinates allosteric regulation of stress signaling.Nature chemical biology · 2024Article
- Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B.Molecular cell · 2024Article
- Identifying molecular subgroups of patients with preeclampsia through bioinformatics.Frontiers in cardiovascular medicine · 2024Article
- The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 10 institutions in 3 countries.
Funding
Abstract
Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) encoding the regulatory subunit of an eIF2α-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation and results in β-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to β-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.