JAK3 is a member of the Janus family of tyrosine kinases, which are involved in cytokine receptor-mediated signaling through the JAK/STAT pathway. JAK3 is believed to be essential for the development of lymphoid cells, especially mature T-cells and NK cells. Missense mutations of JAK3 have been described in approximately 34% of T cell prolymphocytic leukemias, 20% of natural killer cell lymphoma, 10% of T cell acute lymphoblastic leukemia including early T cell precursor T cell ALL and occasional cases of Down syndrome associated -myeloid leukemia, -transient leukemia and -acute megakaryoblastic leukemia. In addition, subclonal, secondary mutations of JAK3 have been reported in approximately 10% of juvenile myelomonocytic leukemia and may occur together with mutations the RAS pathway genes. Mutations of JAK3 are typically activating (gain of function) mutations and are potential therapeutic targets in some settings.

JAK3 is a non-receptor protein tyrosine kinase involved in the interferon-alpha/beta/gamma pathway and is a member of the JAK/STAT signaling pathway. The JAK3 V722I variant has been reported as a likely benign germline polymorphism (ClinVar, https://preview.ncbi.nlm.nih.gov/clinvar/variation/134573/) and also as an acquired somatic variant in some tumors. It has been reported to be an activating variant of JAK3 and initial in vitro studies suggest that this variant may play a role in the regulation of PD-L1 expression. Also, V722I resulted in constitutive phosphorylation of Jak3 and was transforming in cell culture. Clinical correlation is recommended.

This gene is a known cancer gene.

This gene is a known cancer gene.