JAK3 (Janus Kinase 3 or Just Another Kinase 3)

Note	Mostly point mutations were identified affecting all 7 structural JH domains of JAK3.
	Different mutations identified in all of the 7 domains of JAK3. The mutations in "black color" are the mutations reported in JAK3-SCID; "red color and italic" identifies mutations reported in acute megakaryoblastic leukemia; and "orange color and underline" highlights one mutation that has been reported in both JAK3-SCID and acute megakaryoblastic leukemia.
Somatic	Mutations of JAK3 were generally associated with the same cellular phenotype of the more frequently encountered X-linked SCID due to gamma-c deficiency. It was confirmed with the identification of 34 mutations in JAK3-SCID patients from Europe and the US. JAK3-SCID is inherited as autosomal recessive disease. It is estimated to account for approximately 7-14% of heritable SCID. JAK3 mutations are seemingly sporadic, and neither preferential gene locations (i.e. gene "hot-spots") nor founder effects have yet been documented. The majority of JAK3-SCID patients are compound heterozygotes, having inherited a distinct mutation from each parent, although some individuals are homozygous for their mutations as a result of parental consanguinity. Most mutations have dramatic effects on protein expression of JAK3, but some missense mutations or small in-frame deletions allow for some protein expression. These mutations affect kinase activity, receptor binding, and intracellular trafficking. In addition, 7 mutations of JAK3 have been recently described in 5 patients with acute megakaryoblastic leukemia with or without Down syndrome. These mutations are in general activation mutations. The Down syndrome patients presented initially with transient TXT: myeloproliferative disease.

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