JAK2 (janus kinase 2)
2005-09-01 Sabine Strehl AffiliationChildrens Cancer Research Institute, Kinderspitalgasse 6, A-1090 Vienna, Austria
Identity
HGNC
LOCATION
9p24.1
IMAGE
LEGEND
JAK2 (9p24) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
IMAGE
LEGEND
JAK2 (janus kinase 2) Hybridization with JAK2 (9p24) break apart probe (Kreatech, Leica Biosystems Inc., US) showing the JAK2 gene at region 9p24 (red-green or a fused yellow signal) - Courtesy Adriana Zamecnikova.
LOCUSID
ALIAS
JTK10
FUSION GENES
DNA/RNA
Description
25 exons spanning roughly 140 kb of genomic DNA; 5402 bp pre-mRNA; 6 different transcripts, putatively encoding 4 different protein isoforms
Proteins
Description
1132 amino acids; 130,7 kDa; JAK2 contains a central Src homology 2 (SH2) domain, and two C-terminal domains: a tyrosine kinase domain JH1 (also termed PTK or TyrKc domain), and a tyrosine kinase-like domain JH2 (also termed STYKc)
Expression
wide
Localisation
intracellular, possibly membrane associated
Function
protein tyrosine kinase of the non-receptor type that associates with the intracellular domains of cytokine receptors; JAK2 is the predominant JAK kinase activated in response to several growth factors and cytokines such as IL-3, GM-CSF and erythropoietin; it has been found to be constitutively associated with the prolactin receptor and is required for responses to gamma interferon
Mutations
Somatic
A high proportion (> 50%) of patients with myeloproliferative disorders (MPD; (polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis - see below) carry a dominant gain-of-function V617F mutation in the JH2 kinase-like domain of JAK2. This mutation leads to deregulation of the kinase activity, and thus to constitutive tyrosine phosphorylation activity. The incidence of the V617F mutation in different studies ranges from 65-97% in polycythemia vera, from 41-57% in patients with essential thrombocythemia, and from 23-95% in patients with idiopathic myelofibrosis. In MPD the mutation is heterozygous in most patients and homozygous only in a minor subset. Mitotic recombination probably causes both 9p LOH and the transition from heterozygosity to homozygosity. The same mutation was also found in roughly 20% of Ph-negative atypical CML, in more than 10% of CMML, in about 15% of patients with megakaryocytic AML (AML M7), and 1/5 patients with juvenile myelomonocytic leukemia (JMML). The V617F mutation seems to occur exclusively in hematopietic malignancies of the myeloid lineage.
Implicated in
Entity name
Disease
myeloid and lymphoid malignancies; predominantly atypical CML, but also found in (CEL), (secondary) AML, and MDS/MPD; thirteen cases described to date, all male, except for one childhood female case with erythroid leukemia with multiple bone tumors
Prognosis
highly variable; allogeneic stem cell transplantation may be the only curative treatment
Hybrid gene
5 PCM1 3 JAK2; only in some cases the reciprocal 5 JAK2 3 PCM1 is present
Fusion protein
almost the entire PCM1 protein containing multiple coiled-coil domains is fused to the tyrosine kinase C-terminal domains (JH2 and JH1) of JAK2
Oncogenesis
dimerization or oligomerization of the PCM1-JAK2 chimera through one or more of the coiled-coil motifs of PCM1 probably results in the constitutive activation of the tyrosine kinase domain of JAK2
Entity name
Disease
myeloid and lymphoid leukemias; only three cases described to date; one case each: childhood T-ALL, pre B-ALL, atypical CML
Prognosis
unknown
Hybrid gene
5 ETV6 - 3 JAK2
Fusion protein
in the atypical CML the N-terminal HLH of ETV6 is fused to the tyrosine kinase C-terminal domains (JH2 and JH1) of JAK2; in the B-ALL the same ETV6 domain is fused to part of the JH2 and the complete JH1 domain, and in the T-ALL case to the JH1 domain
Oncogenesis
it may be speculated that the HLH domain of ETV6 provides a dimerization interface to the kinase domain of JAK2, which activates JAK2; ETV6-JAK2 transgenic mice generated using a T-ALL specific fusion construct - develop fatal CD8+ acute T-cell leukemia
Entity name
t(9;22)(p24;q11.2) /MPD-- > JAK2-BCR
Disease
atypical CML; only one case described to date
Hybrid gene
5 BCR 3 JAK2; absence of the reciprocal 5 JAK2 3 BCR
Fusion protein
the N-terminal coiled-coil domain of BCR is fused to the JH1 tyrosine kinase C-terminal domain of JAK2
Oncogenesis
constitutive activation of the tyrosine kinase domain of JAK2 mediated through oligomerization through the coiled-coil domain of BCR
Entity name
Polycythemia vera / Essential thrombocythemia / Idiopathic thrombocythemia / Idiopathic myelofibrosis
Note
the V617F mutation in JAK2 could form the basis for a new molecular classification of myeloproliferative disorders
Disease
chronic myeloproliferative syndromes
Oncogenesis
a significant percentage of patients with myeloproliferative disorders carries a dominant gain of function V617F mutation in JAK2; this mutation seems to lead to deregulation of the kinase activity of JAK2, and thus to constitutive tyrosine phosphorylation activity, providing hematopoietic cells with a proliferative and survival advantage
Breakpoints
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16079890 | 2005 | Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. | Antonioli E et al |
| 15781101 | 2005 | Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. | Baxter EJ et al |
| 16091753 | 2005 | The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene. | Bousquet M et al |
| 10845925 | 2000 | TEL-JAK2 transgenic mice develop T-cell leukemia. | Carron C et al |
| 16155011 | 2005 | Genetics of myeloid malignancies: pathogenetic and clinical implications. | Fröhling S et al |
| 15985544 | 2005 | The Jak2V617F mutation, PRV-1 overexpression, and EEC formation define a similar cohort of MPD patients. | Goerttler PS et al |
| 16001431 | 2005 | A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia. | Griesinger F et al |
| 12149229 | 2002 | TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways. | Ho JM et al |
| 15793561 | 2005 | A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. | James C et al |
| 16037387 | 2005 | JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. | Jelinek J et al |
| 16156870 | 2005 | JAK2 V617F Mutation is uncommon in chronic myelomonocytic leukaemia. | Johan MF et al |
| 15920007 | 2005 | Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. | Jones AV et al |
| 16081684 | 2005 | Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2. | Kralovics R et al |
| 9360930 | 1997 | A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. | Lacronique V et al |
| 16115143 | 2005 | Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2(V617F) in granulocytes. | Lasho TL et al |
| 16081687 | 2005 | The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. | Levine RL et al |
| 15837627 | 2005 | Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. | Levine RL et al |
| 16007127 | 2005 | JAK the trigger. | Mahon FX et al |
| 16034466 | 2005 | PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. | Murati A et al |
| 9326218 | 1997 | Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. | Peeters P et al |
| 16123535 | 2005 | Identification of an acquired mutation in Jak2 provides molecular insights into the pathogenesis of myeloproliferative disorders. | Pesu M et al |
| 15805263 | 2005 | The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. | Reiter A et al |
| 9736611 | 1998 | Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes. | Schwaller J et al |
| 15837617 | 2005 | JAKing up hematopoietic proliferation. | Shannon K et al |
| 15860661 | 2005 | The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes. | Steensma DP et al |
| 16156866 | 2005 | The V617F mutation in Jak2 is not found in childhood acute lymphoblastic leukaemia. | Sulong S et al |
| 15970705 | 2005 | JAK2 in myeloproliferative disorders is not just another kinase. | Tefferi A et al |
| 16079889 | 2005 | JAK2 Val617Phe activating tyrosine kinase mutation in juvenile myelomonocytic leukemia. | Tono C et al |
| 15863514 | 2005 | Identification of an acquired JAK2 mutation in polycythemia vera. | Zhao R et al |
Other Information
Locus ID:
NCBI: 3717
MIM: 147796
HGNC: 6192
Ensembl: ENSG00000096968
Variants:
dbSNP: 3717
ClinVar: 3717
TCGA: ENSG00000096968
COSMIC: JAK2
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000096968 | ENST00000381652 | O60674 |
| ENSG00000096968 | ENST00000476574 | A0A1B0GVR5 |
| ENSG00000096968 | ENST00000636127 | A0A1B0GTR9 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37178251 | 2024 | LCN2 Promotes Proliferation and Glycolysis by Activating the JAK2/STAT3 Signaling Pathway in Hepatocellular Carcinoma. | 0 |
| 37594110 | 2024 | Overexpression of SOCS2 Inhibits EMT and M2 Macrophage Polarization in Cervical Cancer via IL-6/JAK2/STAT3 Pathway. | 0 |
| 37883794 | 2024 | PF4 activates the c-Mpl-Jak2 pathway in platelets. | 2 |
| 38006726 | 2024 | Hsa_circ_0013561 promotes progression of nasopharyngeal carcinoma by activating JAK2/STAT3 signaling pathway. | 1 |
| 38104968 | 2024 | A newly identified 45-kDa JAK2 variant with an altered kinase domain structure represents a novel mode of JAK2 kinase inhibitor resistance. | 2 |
| 38154546 | 2024 | PCSK9 regulates myofibroblast transformation through the JAK2/STAT3 pathway to regulate fibrosis after myocardial infarction. | 2 |
| 38191068 | 2024 | Epithelial IL5RA promotes epithelial-mesenchymal transition in pulmonary fibrosis via Jak2/STAT3 cascade. | 0 |
| 38197452 | 2024 | Insights into the role of JAK2-I724T variant in myeloproliferative neoplasms from a unique cohort of New Zealand patients. | 0 |
| 38200372 | 2024 | Identification and validation of the association of Janus kinase 2 mutations with the response to immune checkpoint inhibitor therapy. | 0 |
| 38278152 | 2024 | Proinflammatory phenotype of iPS cell-derived JAK2 V617F megakaryocytes induces fibrosis in 3D in vitro bone marrow niche. | 0 |
| 38308077 | 2024 | Calreticulin and JAK2V617F driver mutations induce distinct mitotic defects in myeloproliferative neoplasms. | 0 |
| 38340948 | 2024 | Altered erythropoiesis via JAK2 and ASXL1 mutations in myeloproliferative neoplasms. | 0 |
| 38342622 | 2024 | Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex. | 1 |
| 38387921 | 2024 | [Comparison of Clinical Characteristics of JAK2, CALR and Tri-Negative Driving Mutant Type in Patients with Essential Thrombocythemia]. | 0 |
| 38411346 | 2024 | Sciellin promotes the development and progression of thyroid cancer through the JAK2/STAT3 signaling pathway. | 0 |
Citation
Sabine Strehl
JAK2 (janus kinase 2)
Atlas Genet Cytogenet Oncol Haematol. 2005-09-01
Online version: http://atlasgeneticsoncology.org/gene/98/jak2-(janus-kinase-2)
Historical Card
1998-02-01 JAK2 (janus kinase 2) by Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
