ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

From OMIM 600555: "Liu et al. (2011) noted that germline mutations in STAT1 underlie susceptibility to 3 different types of infectious disease: mycobacterial diseases, viral diseases, and chronic mucocutaneous candidiasis (CANDF7; 614162). Patients with STAT1 mutations and mycobacterial and/or viral disease do not suffer from chronic mucocutaneous candidiasis, and patients with chronic mucocutaneous candidiasis caused by other STAT1 mutations present no mycobacterial or viral diseases. Overall, mutations impairing STAT1 function confer autosomal dominant or autosomal recessive susceptibility to intracellular agents through impairment of IFNA/IFNB immunity (viral diseases) and/or IFNG immunity (mycobacterial diseases). In contrast, gain-of-function STAT1 mutations confer autosomal dominant chronic mucocutaneous candidiasis due to enhanced STAT1-mediated cellular responses to STAT1-dependent repressors and STAT3-dependent inducers of IL17-producing T cells." Though several missense mutations in STAT1 have been reported in association with autosomal dominant susceptibility to infections, there is not enough evidence at this time to indicate that this phenotype is the result of haploinsufficiency. Evidence currently suggests two mechanisms: autosomal dominant gain-of-function and autosomal recessive due to loss-of-function. The impact of heterozygosity for a some missense mutations is still unclear, with some studies suggesting a dominant-negative effect (PMID: 23585529, 22573496). See also PMID: 23709754, 23534974.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity