TYK2 and Mendelian susceptibility to mycobacterial diseases: Moreover, homozygosity for TYK2 P1104A, which selectively impairs IL-23–dependent IFN-γ production, is a common and highly penetrant genetic etiology of TB, but a rare and weakly penetrant etiology of MSMD (Boisson-Dupuis et al., 2018; Kerner et al., 2019, 2021; Casanova and Abel, 2022).