Alt. symbols: JTK1

Approved name: tyrosine kinase 2
Alt. names: nonreceptor tyrosineprotein kinase TYK2

Location: 19p13.2: 10350528 - 10380608 (-)
Gene type: protein_coding, 35 transcripts.

Scores: LoFtool: 0.209000 | pLI: 0.00431448 | LOEUF: 0.564

HGNC: 12440

NCBI: 7297, RefSeq: NG_007872.1

Ensembl: ENSG00000105397.16

LRG_121 | Status: public

OMIM: 176941

Expression | ProteinAtlas

TYK2 encodes a non-receptor tyrosine kinase of the Janus kinase (JAK) family and plays roles in antiviral responses downstream of cytokine and IFN receptors. TYK2 protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promotes cytokine signals by phosphorylating receptor subunits. It is also a component of both the type I and type III interferon signalling pathways. TYK2 is involved in the Th1 differentiation pathway and RET signalling cascade.

Biallelic frameshift, nonsense, and splice site mutations leading to TYK2 deficiency have previously been associated with primary immunodeficiencies with predisposition to cutaneous viral infection, atypical mycobacteriosis and fungal infection, in the context of autosomal recessive hyperIgE syndrome (AR-HIES) [MIM:611521], but also independently (PMID: 17088085, 22402565, 26304966, 29725107). Homozygosity for the common P1104A variant has been linked to tuberculosis susceptibility (PMID: 310684 74). One heterozygous missense mutation (A53T) was reported for a previously healthy adult patient with herpes simplex encephalitis and associated with significantly impaired CXCL10 and IFN-gamma viral responses (PMID: 26513235). Other studies have associated TYK2 monoallelic gain-of-function (GOF) variants to increased risk for certain blood cancers, such as acute lymphoblastic leukemia (ALL) (PMID: 27733777), and as protective or risk alleles for many autoimmune diseases (i.e. systemic lupus erythematosus, multiple sclerosis, Crohn’s disease, psoriasis, type 1 diabetes, and primary biliary cirrhosis) (PMID: 23359498). While some missense variants are considered to exert gain-of-function or dominant negative effects, others have been characterized as loss-of-function (PMID: 10908660, 14500783, 22744673, 23359498, 23471820). Moreover, TYK2 gene translocations and fusions with the gene NPM1 have been linked to lymphomatoid papulosis. [Load More]