JAK3 Gene - Janus Kinase 3
JAK3: A Key Tyrosine Kinase in Immune Signaling and Severe Combined Immunodeficiency
Gene Information Card
| Symbol | JAK3 |
|---|---|
| Full Name | Janus kinase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 3718 ncbi.nlm.nih.gov/gene/3718 |
| Ensembl ID | ENSG00000105699 |
| UniProt ID | P52333 |
| OMIM ID | 600173 |
| HGNC ID | 6193 |
| Aliases | L-JAK, JAKL, L-JAK kinase |
Description
JAK3 (Janus kinase 3) is a protein-coding gene that encodes a member of the Janus kinase (JAK) family of tyrosine kinases. This enzyme is predominantly expressed in hematopoietic cells and plays a critical role in cytokine receptor signaling via the JAK-STAT pathway. JAK3 associates with the common gamma chain (γc) of cytokine receptors, including those for interleukins IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Mutations in JAK3 cause autosomal recessive severe combined immunodeficiency (SCID), characterized by a lack of T cells and NK cells with normal B cells (T-B+NK- SCID).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe combined immunodeficiency, autosomal recessive, T-cell negative, B-cell positive, NK-cell negative (T-B+NK- SCID) | Loss-of-function mutations in JAK3 disrupt cytokine signaling via the common gamma chain, impairing T-cell and NK-cell development. | ClinVar, OMIM |
| Severe combined immunodeficiency (SCID) | JAK3 deficiency leads to defective JAK-STAT signaling, preventing lymphoid progenitor differentiation. | OMIM #600173 |
| Acute lymphoblastic leukemia (ALL) | Somatic gain-of-function mutations (e.g., R172H) in JAK3 can activate STAT5 signaling, contributing to leukemogenesis. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.8 | Medium |
| Spleen | 10.5 | Medium |
| Lymph node | 9.2 | Medium |
| Thymus | 7.4 | Low |
| Whole blood | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HEK 293 (embryonic kidney) | 2.1 | Low expression |
| Jurkat (T-cell leukemia) | 18.7 | High expression |
| HeLa (cervical carcinoma) | 3.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1715G>A (p.Arg572Gln) | Missense | Pathogenic in SCID | Loss of kinase activity; disrupts ATP binding |
| c.1960C>T (p.Arg654Trp) | Missense | Pathogenic in SCID | Impaired JAK3-STAT5 signaling |
| c.514G>A (p.Val172Met) | Missense | Somatic in ALL | Gain-of-function; constitutive STAT5 activation |
| c.2110C>T (p.Arg704Cys) | Missense | Likely pathogenic | Reduced JAK3 expression and function |
Mutation functional classification
Loss of Function (LOF)
Most JAK3 mutations in SCID are loss-of-function, leading to absent or severely reduced kinase activity and defective cytokine signaling.
Gain of Function (GOF)
Somatic missense mutations (e.g., Val172Met) in hematologic malignancies confer constitutive activation of JAK3 and downstream STAT5.
Dominant Negative (DN)
Some JAK3 mutations may exert dominant-negative effects by forming inactive heterodimers with wild-type JAK3, though this is less common.
View complete mutation data：
Gene Ontology (GO)
Pathways
• JAK-STAT signaling pathway (KEGG hsa04630)
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• IL-2 signaling pathway (Reactome R-HSA-451927)
• IL-7 signaling pathway (Reactome R-HSA-449147)
• Common gamma chain family signaling (Reactome R-HSA-451906)
Protein Summary
JAK3 is a 1124-amino-acid tyrosine kinase with a typical JAK family domain architecture: an N-terminal FERM domain, a SH2-like domain, a pseudokinase domain, and a C-terminal kinase domain. It is essential for signaling through cytokine receptors that utilize the common gamma chain. Upon cytokine binding, JAK3 autophosphorylates and phosphorylates receptor subunits, creating docking sites for STAT transcription factors. JAK3 is predominantly expressed in hematopoietic tissues and is critical for lymphocyte development and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| JAK3 Knockout HEK293 Cell Line | EDJ-KQ17829 | Human | 3718 | Details Get a Quote |
| JAK3 Knockout HCT 116 Cell Line | EDJ-KQ18011 | Human | 3718 | Details Get a Quote |
| JAK3 Knockout HeLa Cell Line | EDJ-KQ53690 | Human | 3718 | Details Get a Quote |
| JAK3 Knockout A-549 Cell Line | EDJ-KQ62167 | Human | 3718 | Details Get a Quote |
| JAK3 (c.3207+101C>G )Point Mutation in HAP1 Cell Line | EDC03517 | Human | 3718 | Details Get a Quote |
| JAK3 (c.3096+18A>G )Point Mutation in HAP1 Cell Line | EDC03518 | Human | 3718 | Details Get a Quote |
| JAK3 (c.1142+13C>A )Point Mutation in HAP1 Cell Line | EDC03519 | Human | 3718 | Details Get a Quote |
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