The signalling enzyme that tells marrow cells to make red cells and platelets; a single mutation (V617F) leaves it switched on in most myeloproliferative neoplasms. This dossier gathers the 5 products (5 approved), 0 trials, 1 pathway and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
JAK2 is a non-receptor tyrosine kinase with a pseudokinase (JH2) domain that normally restrains the kinase (JH1); V617F in JH2 relieves autoinhibition, causing cytokine-independent STAT5/MAPK/PI3K signalling and erythroid/megakaryocytic expansion.
- Polycythaemia vera (~95% V617F, ~3% exon 12)
- Essential thrombocythaemia and primary myelofibrosis (~55-65%)
- Ph-like B-ALL (JAK2 fusions, ~7%)
- Down syndrome ALL (JAK2 R683)
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Myeloproliferative neoplasms | 60-95% | JAK2 V617F by subtype | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Mutation hotspots and which drugs address them
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| V617F 617 | Activating | About 95% of polycythaemia vera and 50 to 60% of essential thrombocythaemia and primary myelofibrosis | Pseudokinase mutation that releases auto-inhibition. The approved JAK inhibitors block the kinase domain and are not mutation-selective; V617F-selective inhibitors are in development. | — | Baxter et al., Lancet 2005 | |
| Exon 12 (N542_E543del, K539L) 540 | Activating | About 3% of polycythaemia vera | V617F-negative PV; same drugs. | — | COSMIC: JAK2 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: COSMIC: JAK2.
Products by modality and phase
Browse products →| Modality | Approved |
|---|---|
| Small molecule 4 | |
| Long-acting mono-pegylated interferon alfa 1 |
Trials
Evidence ranking →No trial in the corpus names this target or one of its products.
Resistance routes that involve this target
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways where it is a node
Pathway-to-drug matrix →- Fibroblast activation, desmoplasia & matrix stiffnessNode: iCAF (IL-6, CXCL12, LIF) · 4 druggable nodes
Tumours recruit the body's repair cells, fibroblasts, and keep them in wound-healing mode forever. The scar tissue they lay down (desmoplasia) squeezes blood vessels shut, walls out immune cells, stiffens the tissue in a way that itself tells cancer cells to grow, and is why pancreatic cancer is so hard to treat.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →- MOMENTUM: momelotinib versus danazol for myelofibrosis patients with anaemia after a prior JAK inhibitor · The Lancet 2023
- COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis · New England Journal of Medicine 2012
Query for this target: (TITLE:"JAK2" OR ABSTRACT:"JAK2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about JAK2, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/jak2.json. Licence CC BY 4.0.