JAK3-gene

The JAG3 gene , also known as the Janus kinase3 gene, is a protein-coding gene located on chromosome 19p13.1. The protein encoded by this gene is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. The Janus kinase3 protein is predominantly expressed in immune cells and transmits a signal in response to their activation via tyrosine phosphorylation by interleukin receptors. An important paralog of the JAK3 gene is JAK2.

Mutations in the JAK3 gene are associated with the following diseases:

Immunodeficiency: Inactivating mutations of JAK3 are known causes of immunodeficiency. Mutations in the common gamma chain (γc) lead to X-linked severe combined immunodeficiency (X-SCID). Because γc associates specifically with JAK3, mutations in JAK3 also lead to SCID.

Activating JAK3 mutations are found in patients with T-cell acute lymphoblastic leukemia (T-ALL). Analysis of sequence data from 419 cases of T-cell acute lymphoblastic leukemia (T-ALL) showed a significant association between SUZ12 and JAK3 mutations (Broux M et al. (2019).

Nk cell enteropathy (Xiao W et al 2019).

T-cell prolymphocytic leukemia (T-PLL) (Bergmann AK et al 2014).

High-grade serous ovarian carcinoma -HGSOC with a 4% mutation frequency (Mittempergher L et al. 2020).

In addition, activating (oncogenic) JAK3 mutations can occur in:

• acute megakaryoblastic leukemia
• juvenile myelomonocytic leukemia
• natural killer T-cell lymphoma (NK/T-lymphoma) as well as in
• extranodal NK/T-cell lymphoma of the nasal type are detected (Sim SH et al. 2017).

Most mutations are located in the pseudokinase and kinase domains of the JAK3 protein.

1. Bergmann AK et al (2014) Recurrent mutation of JAK3 in T-cell prolymphocytic leukemia. Genes Chromosomes Cancer 53:309-316.
2. Mittempergher L et al (2020) Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in the JAK3 gene. PLoS One 15:e0235766.
3. Xiao W et al. (2019) Recurrent somatic JAK3 mutations in NK-cell enteropathy. Blood 134:986-991.
4. Xia D et al. (2019) NK-cell enteropathy and Similar Indolent Lymphoproliferative Disorders: A Case Series With Literature Review. Am J Clin Pathol 151:75-85.