JAK2 gene
The JAK2 gene provides instructions for making a protein that promotes the growth and division of cells, particularly blood cells.
Normal Function
The JAK2 gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. This protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells located within the bone marrow, which have the potential to develop into red blood cells, white blood cells, and platelets.
Health Conditions Related to Genetic Changes
Essential thrombocythemia
Somatic mutations in the JAK2 gene are associated with essential thrombocythemia, a disorder characterized by an increased number of platelets. The most common mutation (Val617Phe or V617F) replaces the amino acid valine with phenylalanine at position 617 in the protein. This mutation is found in approximately half of people with essential thrombocythemia.
The V617F mutation results in a JAK2 protein that is constantly turned on (constitutively activated), leading to the overproduction of abnormal blood cells called megakaryocytes. Because platelets are formed from megakaryocytes, this results in an increased number of platelets, which can cause abnormal blood clotting (thrombosis).
Polycythemia vera
Somatic mutations in the JAK2 gene are associated with polycythemia vera, a disorder characterized by uncontrolled blood cell production. The V617F mutation is found in approximately 96 percent of people with this condition. These mutations result in a constitutively activated JAK2 protein, which improves cell survival and increases blood cell production. This leads to thicker blood that flows more slowly, increasing the risk of abnormal blood clots and preventing organs from receiving enough oxygen.
Primary myelofibrosis
Somatic JAK2 gene mutations are associated with primary myelofibrosis, a condition in which bone marrow is replaced by scar tissue (fibrosis). The V617F mutation is found in approximately half of individuals with this condition. The constitutively active JAK2 protein leads to the overproduction of abnormal megakaryocytes, which stimulate other cells to release collagen. This causes scar tissue formation, preventing the bone marrow from producing enough normal blood cells.
Other disorders
Somatic JAK2 gene mutations are also associated with several related conditions, including:
- Cancer of blood-forming cells (leukemia)
- Other bone marrow disorders
- Budd-Chiari syndrome (a blocked vein in the liver)
Other Names for This Gene
- JAK-2
- JAK2_HUMAN
- Janus kinase 2 (a protein tyrosine kinase)
- JTK10
- tyrosine-protein kinase JAK2
