[5] All STAT molecules are phosphorylated by receptor associated kinases, that causes activation, dimerization by forming homo- or heterodimers and finally translocate to nucleus to work as transcription factors.

[8] STAT1 has a key role in many gene expressions that cause survival of the cell, viability or pathogen response.

[14] In either case, binding of the promoter element leads to an increased expression of ISG (Interferon-Stimulated Genes).

In humans STAT1 has been particularly under strong purifying selection when populations shifted from hunting and gathering to farming, because this went along with a change in the pathogen spectrum.

[18] In knock-out mice prepared in the 90s, a low amount of CD4+ and CD25+ regulatory T-cells and almost no IFNa, b and g response was discovered, which lead to parasital, viral and bacterial infections.

The very first reported case of STAT1 deficiency in human was an autosomal dominant mutation and patients were showing propensity to mycobacterial infections.

2 related patients had a homozygous missense STAT1 mutation which caused impaired splicing, therefore a defect in mature protein.

More recently, two patients have been identified with homozygous STAT-1 mutations who developed both post–BCG vaccination disseminated disease and lethal viral infections.

Very common are also autoimmune symptoms like type 1 diabetes, cytopenia, regression of the thymus or systemic lupus erythematosus.

With various genomic and genetic methods was discovered, that a heterozygous gain of function mutation of STAT1 is a cause of more than a half CMC cases.

Patients with STAT1 gain of function mutation and CMC poorly or not at all respond to treatment with azole drugs such as Fluconazole, Itraconazole or Posaconazole.