TYK2-gene

TYK2 (tyrosine kinase 2) is a protein-coding gene located on chromosome 19p13.2. The encoded protein, a tyrosine kinase belonging to the Janus kinases (JAKs), interacts with the cytoplasmic domain of type I and type II cytokine receptors and mediates cytokine signaling by phosphorylating receptor subunits. It is also a component of the type I and type III interferon signaling pathways, and this tyrosine kinase is thought to play a role in antiviral immunity. An important paralog of this gene is JAK1.

TYK2 is recognized as a susceptibility gene for some inflammatory and autoimmune diseases (AIDs).

Seven TYK2 variants have been associated with autoimmune diseases in Europeans. These include:

• type I diabetes (T1D)
• psoriasis
• multiple sclerosis and
• hyperimmunoglobulin E syndrome (HIES; primary immunodeficiency with elevated IgE)
• immunodeficiency 35 (OMIM: 611521; autosomal recessive primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and severely elevated serum IgE. It is considered a variant of the hyper-IgE syndrome.)

Signaling pathways in this gene family include interleukin-1 signaling pathways. Gene Ontology (GO) annotations associated with this gene include transferase activity, phosphorus-containing group transfer, and protein tyrosine kinase activity.

Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor that has received approval in psoriasis. TYK2 inhibitors represent a new class of small molecules with a unique mechanism of action. TYK2 is an intracellular kinase and mediates signaling of interleukin 23 (IL-23) and other cytokines involved in psoriasis pathogenesis. Deucravacitinib binds highly selectively to TYK2, thereby inhibiting IL-23, IL-12 and type 1 interferon (IFN) signaling and their downstream functions. This controls inflammatory processes in plaque psoriasis.

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3. Kilic S S et al.(2012) A patient with tyrosine kinase 2 deficiency without hyper-IgE syndrome. J Pediat. 160: 1055-1057
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