JAK3 is a functioning gene that comprises 23 exons spanning roughly 21 kb of genomic DNA with an open reading frame of 3372 bp.

4025 bp mRNA. 7 transcript variants encoding 7 distinct proteins.

3 isoforms produced by alternative splicing: JAK3S, JAK3B, JAK3M.

1124 amino acids, 125099 Da. JAK3 is comprised of 7 JAK homology (JH) domains. JH1 contains the C terminus kinase domain and an SH2 or SH3 binding motif; JH2 contains a pseudokinase domain tandemly linked to the N site of the JH1 domain; 5 more JH domains. The N terminus region (JH6 and JH7) is critical for receptor binding and signal transduction.

JAK3 is expressed in 12 normal human tissues (bone marrow, spleen, thymus, brain, spinal cord, heart, skeletal muscle, liver, pancreas, prostate, kidney, and lung). JAK3S is more commonly seen in hematopoietic cells, whereas JAK3B and JAK3M are detected in cells of hematopoietic or epithelial origin.

Intracellular, membrane-associated through association with interleukin (IL) receptor common gamma chain (gamma-c).

Tyrosine kinase of the non-receptor type. Involved in the signaling of ILs that contain the gamma-c chain in their respective receptors, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Induces tyrosine phosphorylation of a number of proteins, of which most widely studied are signal transducers and activators of transcriptions (STAT). JAK3 has also been shown to phosphorylate insulin receptor substrate-1 (IRS-1), IRS-2, and PI3K/Akt.

JAK3 is the most recently identified member of the mammalian Janus kinase subfamily (TYK2, JAK1, JAK2, and JAK3); JAK3 paralogs to JAK1 and JAK2; human JAK3 orthologs to murine Jak3.

Mostly point mutations were identified affecting all 7 structural JH domains of JAK3.

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.