ArticleCell death & disease2021
A family harboring an MLKL loss of function variant implicates impaired necroptosis in diabetes.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Treatment Options for Patients with Maturity-Onset Diabetes of the Young (MODY): A Systematic Review of Literature: 2026 Update.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Pooled it
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- Life-threatening risk factors contribute to the development of diseases with the highest mortality through the induction of regulated necrotic cell death.Cell death & disease · 2025Review
- Emerging role of PANoptosis in kidney diseases: molecular mechanisms and therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2025Review
- Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation.The Biochemical journal · 2024Article
- The role of regulated necrosis in diabetes and its complications.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Mediators of necroptosis: from cell death to metabolic regulation.EMBO molecular medicine · 2024Review
- Article
- A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation.Nature communications · 2023Article
- Incomplete penetrance and variable expressivity in monogenic diabetes; a challenge but also an opportunity.Reviews in endocrine & metabolic disorders · 2023Review
- Role of necroptosis in kidney health and disease.Nature reviews. Nephrology · 2023Review
- MLKL deficiency protects against low-grade, sterile inflammation in aged mice.Cell death and differentiation · 2023Article
- From (Tool)Bench to Bedside: The Potential of Necroptosis Inhibitors.Journal of medicinal chemistry · 2023Review
- Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases.Frontiers in immunology · 2023Review
- Spatiotemporal control of necroptotic cell death and plasma membrane recruitment using engineered MLKL domains.Cell death discovery · 2022Article
- Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options.Journal of personalized medicine · 2022Review
- Membrane permeabilization is mediated by distinct epitopes in mouse and human orthologs of the necroptosis effector, MLKL.Cell death and differentiation · 2022Article
- RIP kinases and necroptosis in aging and aging-related diseases.Life medicine · 2022Review
- Human RIPK3 C-lobe phosphorylation is essential for necroptotic signaling.Cell death & disease · 2022Article
- Rare catastrophes and evolutionary legacies: human germline gene variants in MLKL and the necroptosis signalling pathway.Biochemical Society transactions · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maturity-onset diabetes of the young, MODY, is an autosomal dominant disease with incomplete penetrance. In a family with multiple generations of diabetes and several early onset diabetic siblings, we found the previously reported P33T PDX1 damaging mutation. Interestingly, this substitution was also present in a healthy sibling. In contrast, a second very rare heterozygous damaging mutation in the necroptosis terminal effector, MLKL, was found exclusively in the diabetic family members. Aberrant cell death by necroptosis is a cause of inflammatory diseases and has been widely implicated in human pathologies, but has not yet been attributed functions in diabetes. Here, we report that the MLKL substitution observed in diabetic patients, G316D, results in diminished phosphorylation by its upstream activator, the RIPK3 kinase, and no capacity to reconstitute necroptosis in two distinct MLKL
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