JAK2
Chr 9ADSomaticJanus kinase 2
Also known as: JTK10
The JAK2 protein is a non-receptor tyrosine kinase that mediates cytokine and growth factor signaling by phosphorylating STAT transcription factors and plays a key role in hematopoiesis, immune responses, and chromatin regulation. Somatic mutations cause myeloproliferative disorders including polycythemia vera, myelofibrosis, acute myeloid leukemia, and thrombocythemia, while germline mutations cause autosomal dominant erythrocytosis. The gene is highly constrained against loss-of-function variation (LOEUF 0.341), reflecting its essential role in normal hematopoietic development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
JAK2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Standard Immunosuppressive Therapy Combined With Romiplostim N01 as First-line Treatment for Severe Aplastic Anemia
RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGClonal Hematopoiesis in Giant Cell Arteritis
NOT YET RECRUITINGElotuzumab for the Treatment of JAK2-Mutated Myelofibrosis
ACTIVE NOT RECRUITINGEffects of Ketone Bodies on Insulin Sensitivity
RECRUITINGTasquinimod in Patients with Myelofibrosis Refractory to or Intolerant for JAK2 Inhibition
RECRUITINGPacritinib For Bone Marrow Fibrosis In Patients With Myelofibrosis Who Have Thrombocytopenia
RECRUITINGUnveiling the Germline Predisposition to Myeloproliferative Neoplasms
RECRUITINGRuxolitinib Maintenance Post-Hematopoietic Stem Cell Transplant T-Cell Lymphoma
RECRUITINGA Clinical Trial of TQ05105 Tablets Combined With TQB3617 Capsules in the Treatment of Myelofibrosis (MF)
RECRUITINGFunctional and Phenotypic Characterization of Monocytes in Myeloproliferative Syndromes
RECRUITINGPacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
RECRUITINGExternal Resources
Links to major genomics databases and tools