ArticleThe Journal of experimental medicine2024
Dominant negative OTULIN-related autoinflammatory syndrome.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
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Who cites it
19 citing papers in PubMed, 17 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- 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
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- BIRC3 (Encoding cIAP2) Variants Result in Dysregulated RIPK1 Signaling Leading to Increased Epithelial Cell Death and Are Associated With Monogenic Crohn's Disease.Gastroenterology · 2026Article
- Mechanisms outpacing medicine in autoinflammatory diseases.Frontiers in immunology · 2026Review
- OTULIN: a master regulator of linear ubiquitin homeostasis in immune signaling, inflammation, and disease.Frontiers in immunology · 2026Review
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- 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
- Expanding the phenotypic and genetic spectrum of ORAS with novel homozygous variant in OTULIN gene: a case series and literature review.Pediatric rheumatology online journal · 2025Article
- Insights from the 2024 pediatric rheumatology basic/translational years in review.Pediatric rheumatology online journal · 2025Review
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- Failure to Close: An Unexpected Surgical Complication Reveals OTULIN Haploinsufficiency.ACR open rheumatology · 2025Article
- Contribution of next generation sequencing to the diagnosis of inborn errors of immunity in a pediatric cohort.Frontiers in immunology · 2025Article
- OTULIN-related conditions: Report of a new case and review of the literature using GenIA.Research square · 2024Article
- OTULIN haploinsufficiency predisposes to environmentally directed inflammation.Frontiers in immunology · 2024Article
- OTULIN deficiency: focus on innate immune system impairment.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
OTU deubiquitinase with linear linkage specificity (OTULIN) regulates inflammation and cell death by deubiquitinating linear ubiquitin chains generated by the linear ubiquitin chain assembly complex (LUBAC). Biallelic loss-of-function mutations causes OTULIN-related autoinflammatory syndrome (ORAS), while OTULIN haploinsuffiency has not been associated with spontaneous inflammation. However, herein, we identify two patients with the heterozygous mutation p.Cys129Ser in OTULIN. Consistent with ORAS, we observed accumulation of linear ubiquitin chains, increased sensitivity to TNF-induced death, and dysregulation of inflammatory signaling in patient cells. While the C129S mutation did not affect OTULIN protein stability or binding capacity to LUBAC and linear ubiquitin chains, it did ablate OTULIN deubiquitinase activity. Loss of activity facilitated the accumulation of autoubiquitin chains on LUBAC. Altered ubiquitination of LUBAC inhibits its recruitment to the TNF receptor signaling complex, promoting TNF-induced cell death and disease pathology. By reporting the first dominant negative mutation driving ORAS, this study expands our clinical understanding of OTULIN-associated pathology.
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What Socratic 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 Socratic graph.