While heterozygous germline inactivating mutations in the signal transducer and activator of transcription 3 (STAT3) with dominant negative effect cause autosomal dominant hyper IgE syndrome (188), heterozygous gain-of-function (GOF) mutations in STAT3 result in an ALPS-like phenotype (81). Here, STAT3 is linked to autoimmune lymphoproliferative syndrome.