JAK2是致癌基因，编码蛋白是非受体酪氨酸激酶（一种细胞内激酶），其调节细胞因子信号传导并且需要同源受体响应细胞外细胞因子信号传导。激活的JAK2信号传导对于血细胞（例如红细胞和血小板）的正常产生是必需的。JAK2的激活导致下游效应子（例如STAT3 / 5和MAPK）的募集和磷酸化，使得这些信号传导分子易位至细胞核以激活转录。95％的真性红细胞增多症和50％的原发性血小板减少症和骨髓纤维化恶性肿瘤等骨髓增生性疾病患者中检测到JAK2的功能获得性突变，表明JAK2主要作为致癌基因起作用。在各种白血病和淋巴瘤中也发现了JAK2融合和激活突变。JAK2 V617F是常见的突变，其通过损害激酶的自身抑制结构域激活激酶活性的改变，导致JAK / STAT信号传导途径的组成型激活。但JAK2突变在实体瘤中很少见。

JAK2 is a non-receptor tyrosine kinase that regulates cytokine signaling and requires a cognate receptor to respond to extracellular cytokine signaling. Activated JAK2 signaling is necessary for the normal production of blood cells such as erythrocytes and thrombocytes. Activation of JAK2 leads to the recruitment and phosphorylation of downstream effectors, such as STAT3/5 and MAPK, enabling the translocation of these signaling molecules to the nucleus to activate transcription . Gain-of-function mutations in JAK2 have been identified in patients with myeloproliferative disorders, including 95% of polycythemia vera and 50% of essential thrombocytopenia and myelofibrosis malignancies, suggesting that JAK2 functions predominantly as an oncogene. JAK2 fusions and activating mutations have also been identified in various leukemias and lymphomas. The most commonly identified mutation is JAK2 V617F, an alteration that activates kinase activity by impairing the autoinhibitory domain of the kinase, leading to constitutive activation of the JAK/STAT signaling pathway. Murine models engineered to express the JAK2 V617F mutation develop a myeloproliferative disorder. While JAK2 mutations are rare in solid tumors,

GeneCards OncoKB My Cancer Genome