The cytokine interleukin-21 (IL-21) is closely related to IL-2 and IL-15, and their receptors all share the common cytokine receptor gamma chain, gammac, which is mutated in humans with X-linked severe combined immunodeficiency disease (XSCID).
Mutations in the common gamma chain (gamma c) of cytokine receptors account for human X-linked severe combined immunodeficiency disease. gamma c contributes to ligand binding and signaling as a component of five cytokine receptors: interleukin-2-receptor (IL-2R), IL-4R, IL-7R, IL-9R and IL-15R.
Interleukin-2 (IL-2) receptor gamma chain mutations in X-linked severe combined immunodeficiency disease result in the loss of high-affinity IL-2 receptor binding.
IL-2R-gamma is responsible for the failure of X-linked severe combined immunodeficiency disease T and B lymphocytes to respond to IL-2-dependent signals.