ArticleThe Journal of experimental medicine2011
Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 440 papers, 3 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
440 citing papers in PubMed, 3 syntheses or guidelines pooled it, 792 citations in OpenAlex.
- The T385M STAT1 gain-of-function mutation confers the most severe disease outcomes.Frontiers in immunology · 2025Pooled it
- 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
- JAK-inhibitor treatment induces rapid yet incomplete immune reconstitution in STAT1 gain-of-function.Journal of human immunity · 2026Article
- STAT1 gain-of-function in 12 Moroccan patients: Clinical and genetic insights.Journal of human immunity · 2026Article
- Light-Controlled Assembly and Disassembly of Covalent RNA-Protein Conjugates to Control RNA Base Editing.Molecules (Basel, Switzerland) · 2026Article
- From Validation to Clinical Interpretation: A Flow Cytometric Th17-Cell Assay for STAT1- and STAT3-Related Inborn Errors of Immunity.Scandinavian journal of immunology · 2026Article
- Disseminated Tuberculosis and Early-Onset SLE in a Child with a Novel STAT1 Gain-of-Function Mutation: a Case Report.Journal of clinical immunology · 2026Article
- Actually, what is a gain-of-function mutation?Genetics · 2026Article
- Tracking fungal pathogens on cancer: Oncomicrobes or opportunistic bystanders?PLoS pathogens · 2026Article
- Cell-Intrinsic Type I Interferon Signaling as a Pleiotropic Orchestrator of CD4 T Cell Immunity.Biomolecules · 2026Review
- Decreased IL-17-producing TThe journal of allergy and clinical immunology. Global · 2026Article
- Cytosolic receptors and signaling in antifungal immunity.The EMBO journal · 2025Review
- Clinical and Immunological Impact of JAK Inhibition in Concurrent Down Syndrome and STAT1 Gain of Function.Journal of clinical immunology · 2025Article
- STAT-1 gain-of-function CMC: Remission of Oral Candidiasis during PD-1 Inhibitor Treatment of Oral Cancer.Journal of clinical immunology · 2025Article
- Precision T cell correction platform for inborn errors of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Abundant Yet Aberrant T Helper Cell Responses to Candida albicans Underlie Mucosal Candidiasis in Humans and Mice.European journal of immunology · 2025Article
- A Child with Chronic Mucocutaneous Candidiasis Harbors a Novel Gain-of-Function Mutation in STAT1.Journal of clinical immunology · 2025Article
- Improved outcome of HSCT in STAT1 gain-of-function disease following JAK inhibition bridging.Journal of human immunity · 2025Article
- Review
380 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
66 authors at 17 institutions in 11 countries.
Funding
Abstract
Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 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.