TYK2 Gene: Tyrosine Kinase 2 - Function, Disease Associations, and Clinical Significance
A comprehensive biomedical overview of the TYK2 gene, its protein product, associated diseases, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | TYK2 |
|---|---|
| Full Name | Tyrosine kinase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 7297 ncbi.nlm.nih.gov/gene/7297 |
| Ensembl ID | ENSG00000105397 |
| UniProt ID | P29597 |
| OMIM ID | 176941 |
| HGNC ID | 12440 |
| Aliases | JTK1; IMD35; TYK2_HUMAN |
Description
TYK2 (Tyrosine Kinase 2) is a member of the Janus kinase (JAK) family of non-receptor tyrosine kinases. It plays a critical role in signal transduction from multiple cytokine receptors, including type I and type II interferons, IL-6, IL-10, IL-12, and IL-23. TYK2 is essential for proper immune responses, and its dysfunction is linked to primary immunodeficiencies, autoimmune diseases, and certain cancers. The gene is located on chromosome 19p13.2 and encodes a 1187-amino acid protein with a molecular weight of approximately 133 kDa.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 35 (IMD35) | Loss-of-function mutations in TYK2 lead to impaired cytokine signaling (e.g., IL-12, IL-23, IFN-alpha/beta), causing susceptibility to intracellular bacterial and viral infections. | ClinVar, OMIM |
| Multiple sclerosis (MS) | A common variant (rs34536443, p.Pro1104Ala) in TYK2 reduces kinase activity and is associated with decreased risk of MS, indicating a protective effect. | ClinVar, literature |
| Systemic lupus erythematosus (SLE) | TYK2 variants (e.g., rs2304256) are associated with altered risk of SLE, likely through modulation of type I interferon signaling. | ClinVar, literature |
| Psoriasis | TYK2 variants (e.g., rs34536443) are associated with psoriasis susceptibility; inhibition of TYK2 is a therapeutic target. | ClinVar, literature |
| Inflammatory bowel disease (IBD) | TYK2 polymorphisms have been linked to IBD risk, affecting IL-12/IL-23 signaling. | ClinVar, literature |
| T-cell acute lymphoblastic leukemia (T-ALL) | Activating mutations in TYK2 (e.g., p.Arg425His) have been identified in T-ALL, contributing to oncogenic signaling. | COSMIC, literature |
| Primary cutaneous anaplastic large cell lymphoma | TYK2 fusions and mutations may drive lymphomagenesis via constitutive JAK-STAT activation. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Bone Marrow | 8.7 | Medium |
| Lung | 6.3 | Low |
| Liver | 5.1 | Low |
| Brain | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HeLa (cervical cancer) | 8.9 | Moderate |
| A549 (lung carcinoma) | 6.2 | Low |
| MCF7 (breast cancer) | 5.8 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro1104Ala (rs34536443) | Missense | ~5% in European populations | Reduced kinase activity; protective against MS, psoriasis; associated with increased risk of infections. |
| p.Arg425His | Missense | Rare (somatic in T-ALL) | Activating mutation; enhances JAK-STAT signaling, contributing to oncogenesis. |
| p.Gly363Asp | Missense | Rare (germline in IMD35) | Loss-of-function; impairs IL-12/IL-23 signaling, causing immunodeficiency. |
| p.Arg857Trp | Missense | Rare (somatic in lymphomas) | Likely gain-of-function; promotes cell proliferation. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., p.Gly363Asp, truncations) impair TYK2 kinase activity or stability, leading to defective cytokine signaling (IL-12, IL-23, IFN) and primary immunodeficiency (IMD35). These are typically autosomal recessive.
Gain of Function (GOF)
Gain-of-function mutations (e.g., p.Arg425His) increase kinase activity, leading to constitutive JAK-STAT activation, promoting oncogenesis in hematological malignancies such as T-ALL.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by dimerizing with wild-type TYK2 and reducing overall signaling, though clear examples are limited; further research is needed.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine kinase activity | • ATP binding |
| • signal transducer activity | • cytokine receptor binding |
| • JAK-STAT cascade | • innate immune response |
| • regulation of cell proliferation | • response to interferon-gamma |
| • positive regulation of transcription by RNA polymerase II |
Pathways
• JAK-STAT signaling pathway
• Interferon alpha/beta signaling
• IL-6 signaling pathway
• IL-12 signaling pathway
• IL-23 signaling pathway
• Cytokine-cytokine receptor interaction
Protein Summary
TYK2 is a 1187-amino acid protein with a typical JAK structure: an N-terminal FERM domain, an SH2-like domain, a pseudokinase domain, and a C-terminal tyrosine kinase domain. It associates with cytokine receptors and phosphorylates STAT transcription factors upon ligand binding. TYK2 is ubiquitously expressed but most abundant in hematopoietic cells. Its activity is regulated by phosphorylation and dephosphorylation. Dysregulation of TYK2 is implicated in immune disorders and cancers, making it a therapeutic target (e.g., deucravacitinib for psoriasis).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TYK2 Knockout HEK293 Cell Line | EDJ-KQ17914 | Human | 7297 | Details Get a Quote |
| TYK2 Knockout A-549 Cell Line | EDJ-KQ18137 | Human | 7297 | Details Get a Quote |
| TYK2 Knockout HCT 116 Cell Line | EDJ-KQ47052 | Human | 7297 | Details Get a Quote |
| TYK2 Knockout HeLa Cell Line | EDJ-KQ47053 | Human | 7297 | Details Get a Quote |
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