ArticleThe Journal of experimental medicine2025
The common HAQ STING allele prevents clinical penetrance of COPA syndrome.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Iterative genetic testing identifiesJournal of human immunity · 2026Article
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Hypomorphic STING1/TMEM173 variants may support immuno-metabolic resilience in aging people living with HIV.GeroScience · 2026Article
- Natural Selection of the CommonbioRxiv : the preprint server for biology · 2026Article
- cGAS-STING pathway activation drives the cold-to-hot tumor transition and sensitizes immunotherapy.Cancer biology & medicine · 2026Review
- Paediatric-onset autoimmune cytopenia: How can we reduce the long-term mortality?British journal of haematology · 2026Article
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- Molecular mechanisms regulating cGAS/STING activation in health and disease.The Journal of clinical investigation · 2026Review
- Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026Review
- Interstitial lung disease and the STING pathway.The Journal of clinical investigation · 2026Review
- Toward a monogenic architecture of human infections: From 1996 to 2026.Journal of human immunity · 2026Review
- DNA-PK interacts with cyclic dinucleotides and inhibits type I interferon responses.The Journal of experimental medicine · 2026Article
- The STING HAQ haplotype and clinical non-penetrance in COPA syndrome.The Journal of experimental medicine · 2026Article
- COPA syndrome spans multiple organs but is defined by STING in the lung.Nature reviews. Rheumatology · 2026Article
- Monogenic disorders of immunity: Common variants are not so rare.Cell genomics · 2026Review
- Mechanisms outpacing medicine in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- Cell biological insights into human STING variants.Cell structure and function · 2025Review
- Article
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18 authors.
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Abstract
COPA syndrome, an autosomal-dominant inborn error of immunity, is nonpenetrant in ∼20% of individuals, with no known mediators of protection. Recent studies implicate STING in the pathogenesis of COPA syndrome. We show that the common HAQ STING allele mediates complete clinical protection. We sequenced 35 individuals with COPA mutations, 26 affected patients and 9 unaffected carriers, finding HAQ STING co-segregation with clinical nonpenetrance. Exome sequencing identified only the mutations comprising HAQ STING as variants shared by unaffected carriers and absent in patients. Experimentally, we found that HAQ STING acts dominantly to dampen COPA-dependent STING signaling. Expressing HAQ STING in patient cells rescued the molecular phenotype of COPA syndrome. Our study is the first report of a common and well-tolerated allele mediating complete clinical protection from a severe genetic disorder. Our findings redefine the diagnostic criteria for COPA syndrome, expose functional differences among STING alleles with broad scientific and clinical implications, and reveal a potential universal gene therapy approach for patients.
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