By Oladimeji Ewumi
June 9, 2023
The JAK2 gene is a protein-coding gene of the Janus kinase family. It plays a role in cellular signaling. Evidence notes connections between this gene and some medical conditions.
The JAK2 geneTrusted Source is present on chromosome 9. It produces a protein that sends signals in cells to help control how many blood cells the bone marrow produces.
Variations in this gene may cause the body to produce too many blood cells. Evidence suggests a link between alterations in the JAK2 gene and some types of blood conditions.
This article will provide an overview of the JAK2 gene, including its functions and related medical conditions.
According to a 2014 article, the JAK2 gene instructs cells to make the JAK2 protein. This protein helps control cell growth and division. Specifically, JAK2 proteins help control the activation and production of hematopoietic stem cells.
Hematopoietic stem cellsTrusted Source are immature cells present in bone marrow. They can differentiate into all blood cell types, including red blood cells, white blood cells, and blood platelets.
A 2017 reviewTrusted Source suggests that the JAK2 gene regulates the JAK-STAT signaling pathway — a chain of enzymatic interactions that controls cell division, immunity, cell death, and tumor formation.
Dysregulation of the JAK-STAT pathway can result in immune disorders. The National Library of MedicineTrusted Source notes that the JAK2 gene and the JAK-STAT signaling pathway are therapeutic targets for treating excessive inflammatory responses and viral infections.
The following are the most common functions of the JAK2 gene:
- regulating the production of blood cells
- promoting cellular processes, including cell growth, development, differentiation, and modifications
- mediating essential signaling events in immunity
- acting as a diagnostic biomarker for most myeloproliferative neoplasms (MPNs), which are rare disorders of the bone marrow
Evidence notes an association between the expression of the JAK2 gene and some blood conditions. For example, MPNs are a group of hematopoietic stem cell conditions that arise due to an overproduction of mature blood cells.
JAK2 V617F is the most common alteration of the JAK2 gene present in blood conditions. According to a 2019 study, this alteration has a prevalence rate of 0.2% in the general population.
Primary myelofibrosis
In primary myelofibrosis (PMF), JAK2 gene variations replace typical bone marrow cells with scar tissue. This alteration affects 50%Trusted Source of people with PMF.
These JAK2 variations lead to the overproduction of atypical megakaryocytes that stimulate other cells to release collagen in the bone marrow. This causes scar tissue to form in a process called fibrosis. Due to this fibrosis, the bone marrow cannot produce enough typical blood cells, leading to symptoms of PMF.
Polycythemia vera
Polycythemia vera (PV) occurs when JAK2 overstimulates the production of red blood cells, causing an excess in the circulatory system. About 96%Trusted Source of people with PV have the V617F variation of the JAK2 gene.
Having extra cells in the bloodstream increases the risk of atypical blood clots. In addition, the thicker blood flows more slowly through the vessels, reducing the amount of oxygen in body tissues.
Essential thrombocythemia
In around 50% of people with essential thrombocythemia (ET), the JAK2 V617F alteration results in the body replacing the amino acid valine with phenylalanine. Switching these amino acids results in the continual activation and production of the JAK2 protein, leading to an overproduction of megakaryocytes.
Since platelets form from megakaryocytes, an increased number of platelets may result in more blood clots.
Inflammatory bowel disease (IBD)Trusted Source is a term for two conditions: Crohn’s disease and ulcerative colitis. Both occur due to inflammation of the gastrointestinal tract.
According to a 2016 studyTrusted Source, increased expression of the JAK2 gene may impact inflammatory responses, causing severe gut inflammation in people with IBD.
Research suggests that JAK2 may play a role in other blood disorders, including leukemia and Budd-Chiari syndrome (BCS).
A 2018 studyTrusted Source indicates that JAK2 variation is rare in de novo acute myeloid leukemia, an aggressive cancer of the bone marrow.
Additional research from 2015 that analyzed JAK2 alteration in those with BCS suggests that 20% had latent MPNs. BCS occurs when a blood clot blocks the hepatic veins. This blockage can cause blood to flow back to the liver.
Many clinical trials are focusing on trying to manipulate the JAK2 gene and enzyme to find a better treatment for many related conditions the protein causes.
These suggest that therapeutic approaches targeting the JAK2 signaling pathways may prove Trusted Source effective in inhibiting pathogenic variations, providing new insights for developing pharmacological interventions.
For example, ruxolitinibTrusted Source is part of a Janus kinase inhibitor class of medication doctors prescribe to treat several conditions, including PMF and PV. Some other examples of Janus kinase inhibitors include Trusted Source:
- abrocitinib
- baricitinib
- filgotinib
- delgocitinib
The JAK2 gene is a protein-coding gene of the Janus kinase family. It initiates several cellular signaling processes, including cell division, immunity, and tumor formation.
Evidence notes that problems with this gene can result in the body producing too many blood cells. Medical experts have found links between the JAK2 gene and some blood conditions, including myelofibrosis, polycythemia vera, and thrombocythemia.
Last medically reviewed on June 9, 2023