ArticleThe Journal of experimental medicine2020
Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
What it found
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Who cites it
77 citing papers in PubMed, 115 citations in OpenAlex.
- A systems perspective on monoallelic inborn errors of immunity.Nature genetics · 2026Review
- Functional diversity of natural humanScience advances · 2026Article
- Article
- Two novel kindreds with autosomal recessive STAT2 deficiency.Journal of human immunity · 2026Article
- Familial pulmonary alveolar proteinosis and type I interferonopathy by mutation of STAT2 (TIMS2).The Journal of experimental medicine · 2026Article
- STAT2 R148 variant: A 16th-century founder mutation and clinical response to high-dose JAK inhibitor therapy.Journal of human immunity · 2026Article
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- A novel stop-loss variant in ISG15 causes C-terminal dysfunction and impairs USP18-mediated negative feedback.Frontiers in immunology · 2026Article
- Pharmacological inhibition of USP18 improves antibacterial responses and the intracellular control ofFrontiers in immunology · 2026Article
- Impact of rare JAK/STAT germline mutations on vaccination-induced innate immune responses in a Tyrolian population.International journal of biological sciences · 2026Article
- SAVI: molecular mechanisms, clinical spectrum and precision medicine approaches beyond type-I IFN.Frontiers in immunology · 2026Review
- STAT2 Promotes Tumor Growth in Colorectal Cancer Independent of Type I IFN Receptor Signaling.Current oncology (Toronto, Ont.) · 2025Article
- De novo pathogenic CSF1R variant implicates microglial dysfunction in pathogenesis of febrile infection-related epilepsy syndrome.Epilepsia · 2025Article
- USP18 Deficiency Presenting as Severe Neonatal Encephalopathy: A Case Report and Review of Pseudo-TORCH Syndromes.Cureus · 2025Article
- Allogeneic hematopoietic cell transplantation for autoinflammatory disorders.International journal of hematology · 2025Review
- Malignant JAK-signaling: at the interface of inflammation and malignant transformation.Leukemia · 2025Review
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Infections in Inborn Errors of STATs.Pathogens (Basel, Switzerland) · 2024Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Type I interferonopathies are monogenic disorders characterized by enhanced type I interferon (IFN-I) cytokine activity. Inherited USP18 and ISG15 deficiencies underlie type I interferonopathies by preventing the regulation of late responses to IFN-I. Specifically, USP18, being stabilized by ISG15, sterically hinders JAK1 from binding to the IFNAR2 subunit of the IFN-I receptor. We report an infant who died of autoinflammation due to a homozygous missense mutation (R148Q) in STAT2. The variant is a gain of function (GOF) for induction of the late, but not early, response to IFN-I. Surprisingly, the mutation does not enhance the intrinsic activity of the STAT2-containing transcriptional complex responsible for IFN-I-stimulated gene induction. Rather, the STAT2 R148Q variant is a GOF because it fails to appropriately traffic USP18 to IFNAR2, thereby preventing USP18 from negatively regulating responses to IFN-I. Homozygosity for STAT2 R148Q represents a novel molecular and clinical phenocopy of inherited USP18 deficiency, which, together with inherited ISG15 deficiency, defines a group of type I interferonopathies characterized by an impaired regulation of late cellular responses to IFN-I.
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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.