ArticleThe Journal of experimental medicine2021
Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Pooled it
- Primary atopic disorders: Monogenic insights into immunity.Journal of human immunity · 2026Review
- Novel Partial Loss-of-function STAT3-variant as Cause of Hyper-IgE-Syndrome in a Danish Family with Variable Expressivity.Journal of clinical immunology · 2026Article
- STAT3-Mutated Hyper-IgE Syndrome With Retroperitoneal Abscess in Adolescence.Clinical case reports · 2026Article
- STAT3 regulates NK and NKT cell differentiation through C-X3-C motif chemokine receptor 1 (CX3CR1) in hyper-IgE syndrome.Molecular biomedicine · 2025Article
- Phantom of the immunologic opera: Unmasking the role of innate lymphoid cells (ILC) in inborn errors of immunity (IEI).Journal of human immunity · 2025Review
- Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers.The Journal of experimental medicine · 2025Article
- A Novel Hypomorphic STAT3 Gene Variant in a 7-year-old Male with Hyper-IgE Syndrome.Journal of clinical immunology · 2025Article
- STAT3 haploinsufficiency is associated with autosomal dominant hyper-IgE syndrome.Science advances · 2025Article
- Mouse Model of STAT3 Mutation Resulting in Job's Syndrome Diverges from Human Pathology.International journal of molecular sciences · 2025Article
- Fine mapping of heterozygous IL6ST nonsense variants underlying autosomal dominant hyper-IgE syndrome.JCI insight · 2025Article
- Signal Transducer and Activator of Transcription 3 (STAT3) Variant p.K709N Causes Hyper-IgE Syndrome Likely by Impaired STAT3-Dimer Formation.European journal of immunology · 2025Article
- Pulmonary features and stage of disease in adult patients with hyper-IgE syndrome: a single-centre clinical study and literature review.Orphanet journal of rare diseases · 2025Article
- Dermatologic presentations of hyper IgE syndrome in pediatric patients.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2025Review
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Pulmonary Aspergillosis and Low HIES Score in a Family with STAT3 N-Terminal Domain Mutation.Journal of clinical immunology · 2025Article
- The genetics of hyper IgE syndromes.Frontiers in immunology · 2025Review
- Tail Fin Regeneration in Zebrafish: The Role of Non-canonical Crosstalk Between STAT3 and Vitamin D Pathway.International journal of biological sciences · 2025Article
- In search of a function for human type III interferons: insights from inherited and acquired deficits.Current opinion in immunology · 2024Review
- Functional genomics in inborn errors of immunity.Immunological reviews · 2024Review
Corrections and comments
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Authors and funding
36 authors at 16 institutions in 7 countries.
Funding
Abstract
Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) carry rare heterozygous STAT3 variants. Only six of the 135 in-frame variants reported have been experimentally shown to be dominant negative (DN), and it has been recently suggested that eight out-of-frame variants operate by haploinsufficiency. We experimentally tested these 143 variants, 7 novel out-of-frame variants found in HIES patients, and other STAT3 variants from the general population. Strikingly, all 15 out-of-frame variants were DN via their encoded (1) truncated proteins, (2) neoproteins generated from a translation reinitiation codon, and (3) isoforms from alternative transcripts or a combination thereof. Moreover, 128 of the 135 in-frame variants (95%) were also DN. The patients carrying the seven non-DN STAT3 in-frame variants have not been studied for other genetic etiologies. Finally, none of the variants from the general population tested, including an out-of-frame variant, were DN. Overall, our findings show that heterozygous STAT3 variants, whether in or out of frame, underlie AD-HIES through negative dominance rather than haploinsufficiency.
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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.