Table 1.

JAKs and STATs with associated cytokines and phenotypes

JAK/STAT	Important for signaling by	Knockout mouse phenotype	Genetic links to human disease
JAK1	IFNα/β, IFNγ, IL-2, IL-4, IL-7, IL-9, IL-21, IL-6 family cytokines, IL-10 family cytokines	Perinatally lethal	GOF somatic mutations cause ALL, AML, solid organ malignancies
JAK2	IFNγ, IL-3, IL-5, GM-CSF, EPO, TPO, G-CSF, GH, leptin	Embryonically lethal due to absence of erythropoiesis	GOF mutations cause PCV, MF, ET, hypercoagulable STATe; somatic mutations associated with acute and chronic hematologic malignancies
JAK3	IL-2, IL-4, IL-7, IL-15, IL-21	Defective T and B cell maturation	Loss of function mutation causes severe combined immunodeficiency (SCID), Jacobsen syndrome
TYK2	IFNα/β, IFNγ, IL-12, IL-23	Reduced responses to Type I IFN and IL12, and defective Stat3 activation.	Loss-of function mutation causes primary immunodeficiency
STAT1	All IFNs	Impaired responses to Type I and Type II IFN	LOF mutations confer susceptibility to mycobacterial and viral infections; GOF mutations cause chronic mucocutaneous candidiasis
STAT2	Type I IFNs	Impaired response to Type I IFN and susceptibility to viral infections	Deficiency causes increased susceptibility to viral mutations
STAT3	Il-6 and other gp130 cytokines	Embryonically lethal	LOF mutations cause AD-HIES; GOF somatic mutations strongly associated with LGL
STAT4	IL-12, IL-23, type I interferons	Mutations in mouse inhibit Th1 differentiation	Polymorphisms associated with RA, SLE
STAT5a/STAT5b	IL-2, EPO, TPO, GM-CSF, GH, IL-7	Defective hematopoietic cell lines	Deficiency causes autoimmunity, bleeding diathesis, immunodeficiency and dwarfism; somatic mutations associated with LGL
STAT6	IL-4, IL-13	Mutations in mouse inhibit T helper 2 differentiation	Polymorphisms associated with asthma, atopy, increased levels of IgE