With one possible exception (ZNFX1 deficiency), all genetic defects underlying both isolated and syndromic MSMD perturb IFN-γ immunity (germline mutations of genes encoding IFN-γR1, IFN-γR2, IFN-γ, STAT1, IRF1, JAK1, IL-12Rß1, IL-12Rß2, IL-23R, IL-12p40, TYK2, SPPL2A, IRF8, NEMO, CYBB, ISG15, USP18, RORγT, and T-bet)4–8,15,17–37. Here, TYK2 is linked to Mendelian susceptibility to mycobacterial diseases.