Eighteen of the 19 known MSMD-causing genes encode products involved in the production of interferon-γ (IFN-γ) (IFNG, IL12B, IL12RB1, IL12RB2, IL23R, ISG15, RORC, TBX21, TYK2), cellular responses to IFN-γ (CYBB, JAK1, IFNGR1, IFNGR2, STAT1, USP18), or both (IRF8, NEMO, SPPL2A) (Figure S1A). This evidence concerns the gene SPPL2A and Mendelian susceptibility to mycobacterial diseases.