ArticleThe Journal of biological chemistry2011
Diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl ester lipase gene-maturity onset diabetes of the young (CEL-MODY): a protein misfolding disease.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
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Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Pooled it
- Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis.International journal of cancer · 2022Pooled it
- Novel variation in theFrontiers in endocrinology · 2026Review
- RareBiomedicines · 2025Article
- Early-onset diabetes with low utilization of lipid as an energy source carrying a rare missense mutation in the CEL gene.Endocrinology, diabetes & metabolism case reports · 2025Article
- Decoding MODY: exploring genetic roots and clinical pathways.Diabetology international · 2025Review
- Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene are benign and also likely to arise somatically in the exocrine pancreas.Human molecular genetics · 2024Article
- Article
- Modelling human diabetesFrontiers in endocrinology · 2024Review
- Incomplete penetrance and variable expressivity in monogenic diabetes; a challenge but also an opportunity.Reviews in endocrine & metabolic disorders · 2023Review
- Article
- Identification and characterization of novel carboxyl ester lipase gene variants in patients with different subtypes of diabetes.BMJ open diabetes research & care · 2023Article
- From glucose sensing to exocytosis: takes from maturity onset diabetes of the young.Frontiers in endocrinology · 2023Review
- The genetic risk factor CEL-HYB1 causes proteotoxicity and chronic pancreatitis in mice.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022Article
- Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022Article
- Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young.International journal of molecular sciences · 2022Review
- Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis.Scientific reports · 2022Article
- Misfolding-induced chronic pancreatitis in CPA1 N256K mutant mice is unaffected by global deletion of Ddit3/Chop.Scientific reports · 2022Article
- Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases.The Journal of clinical endocrinology and metabolism · 2022Article
- Abnormal exocrine-endocrine cell cross-talk promotes β-cell dysfunction and loss in MODY8.Nature metabolism · 2022Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CEL-maturity onset diabetes of the young (MODY), diabetes with pancreatic lipomatosis and exocrine dysfunction, is due to dominant frameshift mutations in the acinar cell carboxyl ester lipase gene (CEL). As Cel knock-out mice do not express the phenotype and the mutant protein has an altered and intrinsically disordered tandem repeat domain, we hypothesized that the disease mechanism might involve a negative effect of the mutant protein. In silico analysis showed that the pI of the tandem repeat was markedly increased from pH 3.3 in wild-type (WT) to 11.8 in mutant (MUT) human CEL. By stably overexpressing CEL-WT and CEL-MUT in HEK293 cells, we found similar glycosylation, ubiquitination, constitutive secretion, and quality control of the two proteins. The CEL-MUT protein demonstrated, however, a high propensity to form aggregates found intracellularly and extracellularly. Different physicochemical properties of the intrinsically disordered tandem repeat domains of WT and MUT proteins may contribute to different short and long range interactions with the globular core domain and other macromolecules, including cell membranes. Thus, we propose that CEL-MODY is a protein misfolding disease caused by a negative gain-of-function effect of the mutant proteins in pancreatic tissues.
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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.