ArticleProceedings of the National Academy of Sciences of the United States of America2016
Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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Who cites it
149 citing papers in PubMed, 1 synthesis or guideline pooled it, 275 citations in OpenAlex.
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- A systems perspective on monoallelic inborn errors of immunity.Nature genetics · 2026Review
- Canonical Wnt induction by OTULIN prevents keratinocyte death and skin inflammation.Science advances · 2026Article
- M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress.Cell death and differentiation · 2026Article
- Pyoderma gangrenosum caused by the molecular uncoupling of OTULIN catalytic activity and LUBAC binding.Nature immunology · 2026Article
- Autosomal recessive A20 zinc finger 7 mutation is associated with early-onset lupus-like disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Soluble CD95L triggers Caspase-10-driven reactive oxygen species production in neutrophils and aggravates anti-neutrophil cytoplasmic antibody-vasculitis.Nature communications · 2026Article
- "CANDLE syndrome: A closer look at a rare autoinflammatory disorder".Journal of translational autoimmunity · 2026Review
- Effect of Hydroxytyrosol on OTULIN Levels in Testıcular Tıssue in Experımental Dıabetes Model Induced wıth Streptozotocin.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Mechanisms outpacing medicine in autoinflammatory diseases.Frontiers in immunology · 2026Review
- C-terminal Fragment Generated by HOIL-1 Cleavage Suppresses Inflammatory Responses of Myeloid Cells to Alleviate Colitis.Theranostics · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- OTULIN: a master regulator of linear ubiquitin homeostasis in immune signaling, inflammation, and disease.Frontiers in immunology · 2026Review
- Article
- Human inborn errors of type I interferon-independent intrinsic immunity in nonleukocytic cells.Current opinion in immunology · 2025Review
- The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons.Genomic psychiatry : advancing science from genes to society · 2025Article
- Novel genotypes, phenotypes, and triggers in humans with OTULIN haploinsufficiency.Journal of human immunity · 2025Article
- Update on new autoinflammatory disorders from the 2024 Pediatric Rheumatology European Society Congress.Pediatric rheumatology online journal · 2025Review
- A novel ubiquitination-based molecular signature predicts prognosis in diffuse large B-cell lymphoma.Annals of hematology · 2025Article
- Review
89 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 10 institutions in 3 countries.
Funding
Abstract
Systemic autoinflammatory diseases are caused by mutations in genes that function in innate immunity. Here, we report an autoinflammatory disease caused by loss-of-function mutations in OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one frameshift mutations in one Pakistani and two Turkish families with four affected patients. Patients presented with neonatal-onset fever, neutrophilic dermatitis/panniculitis, and failure to thrive, but without obvious primary immunodeficiency. HEK293 cells transfected with mutated OTULIN had decreased enzyme activity relative to cells transfected with WT OTULIN, and showed a substantial defect in the linear deubiquitination of target molecules. Stimulated patients' fibroblasts and peripheral blood mononuclear cells showed evidence for increased signaling in the canonical NF-κB pathway and accumulated linear ubiquitin aggregates. Levels of proinflammatory cytokines were significantly increased in the supernatants of stimulated primary cells and serum samples. This discovery adds to the emerging spectrum of human diseases caused by defects in the ubiquitin pathway and suggests a role for targeted cytokine therapies.
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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.