ArticleAmerican journal of human genetics2014
Absence of BiP co-chaperone DNAJC3 causes diabetes mellitus and multisystemic neurodegeneration.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Clinical and Molecular Heterogeneity Underlying Monogenic Causes of Pediatric Diabetes Associated to Brain Developmental Disorders.Clinical genetics · 2025Pooled it
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- JNK and p53 cause human and mouse β cell death during excessive unfolded protein response.The Journal of clinical investigation · 2026Article
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- Coordinated expression and assembly of BiP, p58Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Diosmetin Restores Endoplasmic Reticulum Homeostasis to Ameliorate Podocyte Injury in Diabetic Kidney Disease by Targeting DNAJC3.Journal of diabetes research · 2026Article
- A novel homozygous missenseJournal of pediatric endocrinology & metabolism : JPEM · 2025Article
- Autosomal Recessive Cerebellar Ataxias: Translating Genes to Therapies.Annals of neurology · 2025Review
- Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Article
- Giant axonal neuropathy (GAN): cross-sectional data on phenotypes, genotypes, and proteomic signature from a German cohort.Journal of neurology · 2024Article
- Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.Cell metabolism · 2024Article
- Two novel DnaJ chaperone proteins CG5001 and P58IPK regulate the pathogenicity of Huntington's disease related aggregates.Scientific reports · 2024Article
- Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by BiallelicInternational journal of molecular sciences · 2024Article
- Molecular Mimicry between Meningococcal B Factor H-Binding Protein and Human Proteins.Global medical genetics · 2023Article
- Neuronal p58Cells · 2023Article
- Monogenic diabetes.Nature reviews. Disease primers · 2023Review
- Infancy-onset diabetes caused by de-regulated AMPylation of the human endoplasmic reticulum chaperone BiP.EMBO molecular medicine · 2023Article
- The Role of ER Stress in Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome.International journal of molecular sciences · 2022Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Diabetes mellitus and neurodegeneration are common diseases for which shared genetic factors are still only partly known. Here, we show that loss of the BiP (immunoglobulin heavy-chain binding protein) co-chaperone DNAJC3 leads to diabetes mellitus and widespread neurodegeneration. We investigated three siblings with juvenile-onset diabetes and central and peripheral neurodegeneration, including ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy. Exome sequencing identified a homozygous stop mutation in DNAJC3. Screening of a diabetes database with 226,194 individuals yielded eight phenotypically similar individuals and one family carrying a homozygous DNAJC3 deletion. DNAJC3 was absent in fibroblasts from all affected subjects in both families. To delineate the phenotypic and mutational spectrum and the genetic variability of DNAJC3, we analyzed 8,603 exomes, including 506 from families affected by diabetes, ataxia, upper-motor-neuron damage, peripheral neuropathy, or hearing loss. This analysis revealed only one further loss-of-function allele in DNAJC3 and no further associations in subjects with only a subset of the features of the main phenotype. Our findings demonstrate that loss-of-function DNAJC3 mutations lead to a monogenic, recessive form of diabetes mellitus in humans. Moreover, they present a common denominator for diabetes and widespread neurodegeneration. This complements findings from mice in which knockout of Dnajc3 leads to diabetes and modifies disease in a neurodegenerative model of Marinesco-Sjögren syndrome.
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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.