ArticleAmerican journal of human genetics2018
Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 94 papers, 2 of them syntheses that pooled it.
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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
94 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS.Annals of the rheumatic diseases · 2022Pooled it
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- A systems perspective on monoallelic inborn errors of immunity.Nature genetics · 2026Review
- Proteasome mutations associated with CANDLE syndrome cause altered neuronal development by dysregulating polyamine synthesis.The Journal of clinical investigation · 2026Article
- Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle.Nature communications · 2026Article
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- Mouse model of X-linked Alport syndrome with K229X mutation in the COL4A5 gene.Scientific reports · 2026Article
- Monoallelic PSMB8 variants cause PRAAS with immunodeficiency through impaired immunoproteasome assembly.American journal of human genetics · 2026Article
- The homozygous founder Psmb8 variant of Nakajo-Nishimura syndrome/proteasome-associated autoinflammatory syndrome causes panniculitis-associated lipoatrophy and a shortened lifespan in mice.Scientific reports · 2026Article
- Magical moments in protease biology: proteasome autocatalytic activation and PI31-mediated inhibition.Trends in biochemical sciences · 2026Review
- Molecular mechanisms in rare proteasomopathies.EULAR rheumatology open · 2026Review
- Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations.Nature communications · 2025Article
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency.The Journal of allergy and clinical immunology · 2025Article
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Structural Analysis of the 20S Proteasome Using Native Mass Spectrometry and Ultraviolet Photodissociation.Journal of proteome research · 2024Article
- Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives.Genes & diseases · 2024Review
- Article
- Loss-of-Function Variants in CUL3 Cause a Syndromic Neurodevelopmental Disorder.Annals of neurology · 2024Article
- Visualizing chaperone-mediated multistep assembly of the human 20S proteasome.Nature structural & molecular biology · 2024Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 5 institutions in 4 countries.
Funding
Abstract
The proteasome processes proteins to facilitate immune recognition and host defense. When inherently defective, it can lead to aberrant immunity resulting in a dysregulated response that can cause autoimmunity and/or autoinflammation. Biallelic or digenic loss-of-function variants in some of the proteasome subunits have been described as causing a primary immunodeficiency disease that manifests as a severe dysregulatory syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE). Proteasome maturation protein (POMP) is a chaperone for proteasome assembly and is critical for the incorporation of catalytic subunits into the proteasome. Here, we characterize and describe POMP-related autoinflammation and immune dysregulation disease (PRAID) discovered in two unrelated individuals with a unique constellation of early-onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and autoimmunity. We also begin to delineate a complex genetic mechanism whereby de novo heterozygous frameshift variants in the penultimate exon of POMP escape nonsense-mediated mRNA decay (NMD) and result in a truncated protein that perturbs proteasome assembly by a dominant-negative mechanism. To our knowledge, this mechanism has not been reported in any primary immunodeficiencies, autoinflammatory syndromes, or autoimmune diseases. Here, we define a unique hypo- and hyper-immune phenotype and report an immune dysregulation syndrome caused by frameshift mutations that escape NMD.
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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.