ArticleHuman mutation2012
Dominant-negative STAT1 SH2 domain mutations in unrelated patients with Mendelian susceptibility to mycobacterial disease.
Article in Human mutation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China.Frontiers in immunology · 2022Pooled it
- Clinical Relevance of Gain- and Loss-of-Function Germline Mutations in STAT1: A Systematic Review.Frontiers in immunology · 2021Pooled it
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- Review
- Article
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- A Norwegian cohort with STAT1-related disease - further expanding the clinical phenotype.Frontiers in immunology · 2025Article
- Genetic causes of primary immunodeficiency in the Jordanian population.Biomedical reports · 2024Article
- Deacetylase Sirtuin 1 mitigates type I IFN- and type II IFN-induced signaling and antiviral immunity.Journal of virology · 2024Article
- Inborn errors of immunity: an expanding universe of disease and genetic architecture.Nature reviews. Genetics · 2024Review
- Case report: A novelFrontiers in immunology · 2024Article
- JAKs and STATs from a Clinical Perspective: Loss-of-Function Mutations, Gain-of-Function Mutations, and Their Multidimensional Consequences.Journal of clinical immunology · 2023Review
- Inherited human ZNF341 deficiency.Current opinion in immunology · 2023Review
- Inborn errors of immunity with loss- and gain-of-function germline mutations in STAT1.Clinical and experimental immunology · 2023Review
- Inborn Errors of Immunity Causing Pediatric Susceptibility to Fungal Diseases.Journal of fungi (Basel, Switzerland) · 2023Review
- Genetic and Functional Identifying of Novel STAT1 Loss-of-Function Mutations in Patients with Diverse Clinical Phenotypes.Journal of clinical immunology · 2022Article
- A novel STAT1 loss-of-function mutation associated with Mendelian susceptibility to mycobacterial disease.Frontiers in cellular and infection microbiology · 2022Article
- Nuclear ADP-ribosylation drives IFNγ-dependent STAT1α enhancer formation in macrophages.Nature communications · 2021Article
- IL-2 Signaling Axis Defects: How Many Faces?Frontiers in pediatrics · 2021Review
- IRAK4 Deficiency Presenting with Anti-NMDAR Encephalitis and HHV6 Reactivation.Journal of clinical immunology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 9 institutions in 4 countries.
Funding
Abstract
Patients carrying two loss-of-function (or hypomorphic) alleles of STAT1 are vulnerable to intracellular bacterial and viral diseases. Heterozygosity for loss-of-function dominant-negative mutations in STAT1 is responsible for autosomal dominant (AD) Mendelian susceptibility to mycobacterial disease (MSMD), whereas heterozygosity for gain-of-function loss-of-dephosphorylation mutations causes AD chronic mucocutaneous candidiasis (CMC). The two previously reported types of AD MSMD-causing STAT1 mutations are located in the tail segment domain (p.L706S) or in the DNA-binding domain (p.E320Q and p.Q463H), whereas the AD CMC-causing mutations are located in the coiled-coil domain. We identified two cases with AD-STAT1 deficiency in two unrelated patients from Japan and Saudi Arabia carrying heterozygous missense mutations affecting the SH2 domain (p.K637E and p.K673R). p.K673R is a hypomorphic mutation that impairs STAT1 tyrosine phosphorylation, whereas the p.K637E mutation is null and affects both STAT1 phosphorylation and DNA-binding activity. Both alleles are dominant negative and result in impaired STAT1-mediated cellular responses to interferon (IFN)-γ and IL-27. In contrast, STAT1-mediated cellular responses against IFN-α and IFN-λ1 were preserved at normal levels in patients' cells. We describe here the first dominant mutations in the SH2 domain of STAT1, revealing the importance of this domain for tyrosine phosphorylation and DNA binding, as well as for antimycobacterial immunity.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.