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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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JAK2
Janus kinase 2
Chromosome 9 Β· 9p24.1
NCBI Gene: 3717Ensembl: ENSG00000096968.15HGNC: HGNC:6192UniProt: A8K910
1,812PubMed Papers
25Diseases
31Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisHub GeneKinaseOncogene
RESEARCH IMPACT
Highly Studied
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
erythropoietin-mediated signaling pathwaygranulocyte-macrophage colony-stimulating factor signaling pathwayinterleukin-3-mediated signaling pathwaypositive regulation of platelet aggregationpolycythemia veraprimary myelofibrosismyelofibrosismyeloproliferative disorder
✦AI Summary

JAK2 is a non-receptor tyrosine kinase that mediates signal transduction from multiple cytokine receptors including those for erythropoietin, growth hormone, prolactin, and interferons 12. Upon ligand binding, JAK2 phosphorylates specific tyrosine residues on receptor cytoplasmic tails, creating docking sites for STAT proteins, which JAK2 then phosphorylates 13. Activated STATs translocate to the nucleus to drive gene transcription regulating cell growth, differentiation, and immune responses 1. JAK2 also functions in chr9 regulation by phosphorylating histone H3 at tyrosine 41, promoting CBX5 exclusion and chr9 remodeling 4. Acquired JAK2 mutations, particularly the V617F mutation in exon 14 and various exon 12 mutations, cause myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocytosis, and primary myelofibrosis 56. These mutations constitutively activate JAK2 kinase activity, driving excessive erythropoiesis and thrombocytosis 5. JAK2 mutations are also associated with Budd-Chiari syndrome through mechanisms including endothelial damage and increased blood cell adhesion 7. JAK2 has emerged as an important therapeutic target in MPN management 89.

Sources cited
1
JAK2 associates with type I and II receptors and phosphorylates STAT proteins
PMID: 15690087
2
JAK2 mediates erythropoietin receptor signaling through STAT5 phosphorylation
PMID: 9657743
3
JAK2 phosphorylates STAT proteins recruited to receptor sites
PMID: 9618263
4
JAK2 phosphorylates histone H3 tyrosine 41 in chromatin regulation
PMID: 19783980
5
JAK2 exon 12 mutations cause polycythemia vera and perturb erythropoiesis
PMID: 21674578
6
JAK2 V617F mutation is a driver mutation in myeloproliferative neoplasms
PMID: 30695513
7
JAK2 V617F mutation associates with Budd-Chiari syndrome through thrombogenesis
PMID: 39231710
8
JAK2 activation is identified as underlying defect in myeloproliferative disease
PMID: 16007127
9
JAK2 mutations cause heterogeneous myeloproliferative neoplasms
PMID: 23681871
Disease Associationsβ“˜25
polycythemia veraOpen Targets
0.80Strong
primary myelofibrosisOpen Targets
0.75Strong
myelofibrosisOpen Targets
0.73Strong
myeloproliferative disorderOpen Targets
0.72Strong
neoplasmOpen Targets
0.70Strong
SplenomegalyOpen Targets
0.69Moderate
acute myeloid leukemiaOpen Targets
0.67Moderate
ulcerative colitisOpen Targets
0.67Moderate
cancerOpen Targets
0.66Moderate
essential thrombocythemiaOpen Targets
0.63Moderate
hematologic diseaseOpen Targets
0.62Moderate
thrombocythemia 3Open Targets
0.62Moderate
rheumatoid arthritisOpen Targets
0.62Moderate
hemorrhagic diseaseOpen Targets
0.58Moderate
atopic eczemaOpen Targets
0.57Moderate
Crohn's diseaseOpen Targets
0.57Moderate
Eczematoid dermatitisOpen Targets
0.55Moderate
HepatomegalyOpen Targets
0.54Moderate
polycythemiaOpen Targets
0.54Moderate
graft versus host diseaseOpen Targets
0.53Moderate
Budd-Chiari syndromeUniProt
Leukemia, acute myelogenousUniProt
MyelofibrosisUniProt
Polycythemia veraUniProt
Thrombocythemia 3UniProt
Pathogenic Variants8
NM_004972.4(JAK2):c.1849G>T (p.Val617Phe)Pathogenic
Acquired polycythemia vera|Primary myelofibrosis|Acute myeloid leukemia|Budd-Chiari syndrome, susceptibility to, somatic|Thrombocythemia 3|Primary familial polycythemia due to EPO receptor mutation|Myeloproliferative disorder|6 conditions|Splenomegaly;Primary myelofibrosis|Polycythemia|not provided|JAK2-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 617
NM_004972.4(JAK2):c.2813G>A (p.Arg938Gln)Likely pathogenic
Thrombocythemia 3
β˜…β˜†β˜†β˜†2025β†’ Residue 938
NM_004972.4(JAK2):c.3284C>T (p.Pro1095Leu)Likely pathogenic
Acquired polycythemia vera
β˜…β˜†β˜†β˜†2024β†’ Residue 1095
NM_004972.4(JAK2):c.2600G>A (p.Arg867Gln)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 867
NM_004972.4(JAK2):c.226+1G>TLikely pathogenic
See cases|Hepatocellular carcinoma
β˜…β˜†β˜†β˜†2023
NM_004972.4(JAK2):c.1849G>A (p.Val617Ile)Pathogenic
Thrombocythemia 3
β˜†β˜†β˜†β˜†2012β†’ Residue 617
NM_004972.4(JAK2):c.1615_1616inv (p.Lys539Leu)Pathogenic
ERYTHROCYTOSIS, JAK2-RELATED, SOMATIC
β˜†β˜†β˜†β˜†2007β†’ Residue 539
NM_004972.4(JAK2):c.1821G>C (p.Lys607Asn)Pathogenic
Acute myeloid leukemia
β˜†β˜†β˜†β˜†2006β†’ Residue 607
View on ClinVar β†—
Drug Targets31
AC-430Phase I
Tyrosine-protein kinase JAK2 inhibitor
childhood leukemia
AT-9283Phase III
Serine/threonine-protein kinase Aurora-A inhibitor
AZD-1480Phase II
Tyrosine-protein kinase JAK2 inhibitor
BARICITINIBApproved
Tyrosine-protein kinase JAK1 inhibitor
juvenile idiopathic arthritis
BMS-911543Phase II
Tyrosine-protein kinase JAK2 inhibitor
myelofibrosis
CT-1578Phase I
Macrophage colony stimulating factor receptor inhibitor
DELGOCITINIBApproved
Janus Kinase (JAK) inhibitor
atopic eczema
DEURUXOLITINIB PHOSPHATEApproved
Tyrosine-protein kinase TYK2 inhibitor
alopecia areata
FEDRATINIBApproved
Tyrosine-protein kinase JAK2 inhibitor
polycythemia vera
FEDRATINIB HYDROCHLORIDEApproved
Tyrosine-protein kinase JAK2 inhibitor
FILGOTINIBPhase III
Tyrosine-protein kinase JAK2 inhibitor
rheumatoid arthritis
FILGOTINIB MALEATEApproved
Tyrosine-protein kinase JAK2 inhibitor
rheumatoid arthritis
GANDOTINIBPhase II
Tyrosine-protein kinase JAK2 inhibitor
breast cancer
GUSACITINIBPhase II
Janus Kinase (JAK) inhibitor
Eczematoid dermatitis
IZENCITINIBPhase II/III
Janus Kinase (JAK) inhibitor
ulcerative colitis
LESTAURTINIBApproved
Nerve growth factor receptor Trk-A inhibitor
acute myeloid leukemia by FAB classification
MOMELOTINIBApproved
Activin receptor type-1 inhibitor
myelofibrosis
MOMELOTINIB DIHYDROCHLORIDE MONOHYDRATEApproved
Activin receptor type-1 inhibitor
myelofibrosis
NEZULCITINIBPhase II
Janus Kinase (JAK) inhibitor
COVID-19
NS-018Phase II
Tyrosine-protein kinase JAK2 inhibitor
PACRITINIBApproved
Activin receptor type-1 inhibitor
myelofibrosis
PACRITINIB CITRATEApproved
Activin receptor type-1 inhibitor
polycythemia vera
PEFICITINIBPhase III
Janus Kinase (JAK) inhibitor
psoriasis vulgaris
RUXOLITINIBApproved
Tyrosine-protein kinase JAK1 inhibitor
essential thrombocythemia
RUXOLITINIB PHOSPHATEApproved
Tyrosine-protein kinase JAK1 inhibitor
graft versus host disease
TOFACITINIBApproved
Janus Kinase (JAK) inhibitor
rheumatoid arthritis
TOFACITINIB CITRATEApproved
Janus Kinase (JAK) inhibitor
UPADACITINIBApproved
Tyrosine-protein kinase JAK1 inhibitor
rheumatoid arthritis
UPADACITINIB HEMIHYDRATEApproved
Tyrosine-protein kinase JAK1 inhibitor
rheumatoid arthritis
XL-019Phase III
Tyrosine-protein kinase JAK2 inhibitor
ZOTIRACICLIBPhase I/II
Cyclin-dependent kinase 1 inhibitor
anaplastic astrocytoma
Related Genes
CISHProtein interaction100%CSF2Protein interaction100%CSH2Protein interaction100%EPOProtein interaction100%IL3Protein interaction100%IL5Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
76%
Lung
63%
Ovary
44%
Brain
27%
Liver
14%
Gene Interaction Network
Click a node to explore
JAK2CISHCSF2CSH2EPOIL3IL5
PROTEIN STRUCTURE
Preparing viewer…
PDB8BXH Β· 1.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.85LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.62 [0.46–0.85]
RankingsWhere JAK2 stands among ~20K protein-coding genes
  • #64of 20,598
    Most Researched1,812 Β· top 1%
  • #86of 1,025
    FDA-Approved Drug Targets17 Β· top 10%
  • #3,010of 5,498
    Most Pathogenic Variants8
  • #7,335of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedJAK2
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
The JAK2 exon 12 mutations: a comprehensive review.
PMID: 21674578
Am J Hematol Β· 2011
1.00
2
Hidden conformational codes.
PMID: 37995103
Blood Β· 2023
0.90
3
JAK2 and MPL gene mutations in V617F-negative myeloproliferative neoplasms.
PMID: 19643476
Leuk Res Β· 2010
0.84
4
Aspirin use in essential thrombocythemia: Once-daily or twice-daily or not at all?
PMID: 38752361
Am J Hematol Β· 2024
0.82
5
[JAK2, CALR].
PMID: 30695513
Rinsho Byori Β· 2017
0.80