Defects in cytokine receptor signaling responsible for SCID phenotypes. (A) Most cytokine receptors are heterodimers or heterotrimers whose cytoplasmic regions are accompanied by JAK kinases which in turn activate STAT transcription factor. Proper functionality of these components leads to the development of normal and functional T, B, and NK cells. (B) Mutation in IL2RG inhibits the production of mature NK and T cells. (C) Mutations in JAK3 also prevent the development of mature NK and T cells. (D) Mutation in IL-7Rα chain affects only IL-7 signaling and blights T cell production (mutated molecules are shown with dashed outline).