JAK3 is solely activated by type I cytokine receptors featuring a common γ-chain (γc) subunit that are activated by IL-2, IL-4, IL-7, IL-9, IL-15, and IL-217; mutations in either the γ-chain or JAK3 have been identified in humans as a cause of severe combined immunodeficiency disease (SCID), which manifests as a depletion of T, B, and natural killer (NK) cells with no other defects7,8. Here, JAK3 is linked to severe combined immunodeficiency.