While overexpression of WT SH2B3 was able to partially suppress STAT1-mediated γ-activated sequence (GAS) activity in HEK293 cells stimulated with IFN-γ, this regulation was lost in cells overexpressing all rare SLE patient variants, except A536T (Fig. 1 D and Fig. S1 A). Here, IFNG is linked to systemic lupus erythematosus.