JAK2 (janus kinase 2)

2005-09-01   Sabine Strehl 

Childrens Cancer Research Institute, Kinderspitalgasse 6, A-1090 Vienna, Austria


Atlas Image
JAK2 (9p24) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Atlas Image
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.



25 exons spanning roughly 140 kb of genomic DNA; 5402 bp pre-mRNA; 6 different transcripts, putatively encoding 4 different protein isoforms


Atlas Image


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)




intracellular, possibly membrane associated


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


JAK2 belongs to the janus kinase subfamily; so far four mammalian JAKs have been identified (JAK1, JAK2, JAK3, and TYK2); human JAK2 is > 90% identical to the mouse and the rat JAK2 homologs.



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
t(8;9)(p21-22;p24) / acute leukaemias -- > PCM1-JAK2
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
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
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
t(9;12)(p24;p13) / acute leukaemias --> iJAK2 /ETV6
myeloid and lymphoid leukemias; only three cases described to date; one case each: childhood T-ALL, pre B-ALL, atypical CML
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
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
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
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
the V617F mutation in JAK2 could form the basis for a new molecular classification of myeloproliferative disorders
chronic myeloproliferative syndromes
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


Atlas Image


Pubmed IDLast YearTitleAuthors
160798902005Clinical implications of the JAK2 V617F mutation in essential thrombocythemia.Antonioli E et al
157811012005Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.Baxter EJ et al
160917532005The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene.Bousquet M et al
108459252000TEL-JAK2 transgenic mice develop T-cell leukemia.Carron C et al
161550112005Genetics of myeloid malignancies: pathogenetic and clinical implications.Fröhling S et al
159855442005The Jak2V617F mutation, PRV-1 overexpression, and EEC formation define a similar cohort of MPD patients.Goerttler PS et al
160014312005A 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
121492292002TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways.Ho JM et al
157935612005A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.James C et al
160373872005JAK2 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
161568702005JAK2 V617F Mutation is uncommon in chronic myelomonocytic leukaemia.Johan MF et al
159200072005Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders.Jones AV et al
160816842005Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2.Kralovics R et al
93609301997A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.Lacronique V et al
161151432005Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2(V617F) in granulocytes.Lasho TL et al
160816872005The 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
158376272005Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.Levine RL et al
160071272005JAK the trigger.Mahon FX et al
160344662005PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation.Murati A et al
93262181997Fusion 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
161235352005Identification of an acquired mutation in Jak2 provides molecular insights into the pathogenesis of myeloproliferative disorders.Pesu M et al
158052632005The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.Reiter A et al
97366111998Transformation 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
158376172005JAKing up hematopoietic proliferation.Shannon K et al
158606612005The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes.Steensma DP et al
161568662005The V617F mutation in Jak2 is not found in childhood acute lymphoblastic leukaemia.Sulong S et al
159707052005JAK2 in myeloproliferative disorders is not just another kinase.Tefferi A et al
160798892005JAK2 Val617Phe activating tyrosine kinase mutation in juvenile myelomonocytic leukemia.Tono C et al
158635142005Identification of an acquired JAK2 mutation in polycythemia vera.Zhao R et al

Other Information

Locus ID:

NCBI: 3717
MIM: 147796
HGNC: 6192
Ensembl: ENSG00000096968


dbSNP: 3717
ClinVar: 3717
TCGA: ENSG00000096968


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Jak-STAT signaling pathwayKEGGko04630
Adipocytokine signaling pathwayKEGGko04920
Jak-STAT signaling pathwayKEGGhsa04630
Adipocytokine signaling pathwayKEGGhsa04920
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Cholinergic synapseKEGGhsa04725
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
JAK-STAT signalingKEGGhsa_M00684
JAK-STAT signalingKEGGM00684
Diseases of signal transductionREACTOMER-HSA-5663202
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
RAF activationREACTOMER-HSA-5673000
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Interferon SignalingREACTOMER-HSA-913531
Interferon gamma signalingREACTOMER-HSA-877300
Regulation of IFNG signalingREACTOMER-HSA-877312
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Interleukin-6 signalingREACTOMER-HSA-1059683
Growth hormone receptor signalingREACTOMER-HSA-982772
Prolactin receptor signalingREACTOMER-HSA-1170546
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
GPVI-mediated activation cascadeREACTOMER-HSA-114604
Factors involved in megakaryocyte development and platelet productionREACTOMER-HSA-983231
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
RAF-independent MAPK1/3 activationREACTOMER-HSA-112409
MAPK3 (ERK1) activationREACTOMER-HSA-110056
MAPK1 (ERK2) activationREACTOMER-HSA-112411
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G-protein beta:gamma signallingREACTOMER-HSA-397795
G beta:gamma signalling through PI3KgammaREACTOMER-HSA-392451
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
RMTs methylate histone argininesREACTOMER-HSA-3214858
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Interleukin-6 family signalingREACTOMER-HSA-6783589
IL-6-type cytokine receptor ligand interactionsREACTOMER-HSA-6788467
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
RET signalingREACTOMER-HSA-8853659
Oncogenic MAPK signalingREACTOMER-HSA-6802957
Signaling by RAS mutantsREACTOMER-HSA-6802949
Signaling by moderate kinase activity BRAF mutantsREACTOMER-HSA-6802946
Paradoxical activation of RAF signaling by kinase inactive BRAFREACTOMER-HSA-6802955
Signaling by BRAF and RAF fusionsREACTOMER-HSA-6802952
Th1 and Th2 cell differentiationKEGGko04658
Th1 and Th2 cell differentiationKEGGhsa04658
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
185873942008Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.951
158581872005A gain-of-function mutation of JAK2 in myeloproliferative disorders.857
157935612005A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera.826
157811012005Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.811
158376272005Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.758
194744262009Mutation in TET2 in myeloid cancers.536
216331652011The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors.334
206281452010Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.326
172679062007JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis.269
197839802009JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin.245


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 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France