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The official name of this gene is “isocitrate dehydrogenase 2 (NADP+), mitochondrial.”
IDH2 is the gene's official symbol. The IDH2 gene is also known by other names, listed below.
The IDH2 gene provides instructions for making an enzyme called isocitrate dehydrogenase 2. This enzyme is found in mitochondria, which are the energy-producing centers within cells. Within mitochondria, the enzyme participates in reactions that produce energy for cell activities. Specifically, isocitrate dehydrogenase 2 normally converts a compound called isocitrate to another compound called 2-ketoglutarate. A series of additional enzymes further process 2-ketoglutarate to produce energy. The conversion reaction also produces a molecule called NADPH, which is necessary for many cellular processes and helps protect cells from potentially harmful molecules called reactive oxygen species.
At least two mutations in the IDH2 gene have been found to cause a type of 2-hydroxyglutaric aciduria known as D-2-hydroxyglutaric aciduria (D-2-HGA) type II. This condition has a variety of signs and symptoms that result primarily from progressive damage to the brain beginning early in life.
The mutations that cause D-2-HGA type II are present in all of an affected person's cells. These mutations prevent isocitrate dehydrogenase 2 from carrying out its usual activity, the conversion of isocitrate to 2-ketoglutarate. Instead, the altered enzyme takes on a new, abnormal function: the production of a compound called D-2-hydroxyglutarate. Because the genetic changes lead to an enzyme with a new function, they are classified as "gain-of-function" mutations.
In people with D-2-HGA type II, D-2-hydroxyglutarate builds up abnormally in cells. At high levels, this compound can damage cells and lead to cell death. Brain cells appear to be the most vulnerable to the toxic effects of this compound, which may explain why the signs and symptoms of D-2-HGA type II primarily involve the brain. However, some people with this form of the disorder also have a weakened and enlarged heart (cardiomyopathy). It is unclear why an accumulation of D-2-hydroxyglutarate may be associated with cardiomyopathy.
Mutations in the IDH2 gene have been identified in some people with a form of blood cancer known as cytogenetically normal acute myeloid leukemia (CN-AML). While large chromosomal abnormalities can be involved in the development of acute myeloid leukemia, about half of cases do not have these abnormalities; these are classified as CN-AML. Nearly 20 percent of people with CN-AML have a mutation in the IDH2 gene.
The IDH2 gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. These mutations change single protein building blocks (amino acids) in the isocitrate dehydrogenase 2 enzyme. Like the genetic changes that cause D-2-HGA type II (described above), the IDH2 gene mutations found in CN-AML are gain-of-function mutations. These mutations alter the function of isocitrate dehydrogenase 2 such that it abnormally produces D-2-hydroxyglutarate. Studies suggest that an increase in D-2-hydroxyglutarate may interfere with the process that determines the type of cell an immature cell will ultimately become (cell fate determination). Instead of becoming normal mature cells, immature blood cells with somatic IDH2 gene mutations become cancerous and divide uncontrollably, which plays a role in the development of CN-AML.
Somatic mutations in the IDH2 gene have been associated with other forms of cancer, including brain tumors called gliomas. They have also been associated with primary myelofibrosis, a cancer-related condition that affects the function of bone marrow and the production of new blood cells.
Like the genetic changes that cause D-2-HGA type II and CN-AML (described above), the IDH2 gene mutations found in these cancers are gain-of-function mutations that lead to the abnormal production of D-2-hydroxyglutarate. As in CN-AML, D-2-hydroxyglutarate likely blocks the maturation of cells, resulting in overproduction of immature cells and formation of tumors. It is unclear why IDH2 gene mutations have been found in only these few types of cancer, and it is also unknown why people with D-2-HGA type II do not appear to have an increased risk of developing these cancers.
Cytogenetic Location: 15q26.1
Molecular Location on chromosome 15: base pairs 90,083,977 to 90,102,553
The IDH2 gene is located on the long (q) arm of chromosome 15 at position 26.1.
More precisely, the IDH2 gene is located from base pair 90,083,977 to base pair 90,102,553 on chromosome 15.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about IDH2 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; aciduria ; acute ; acute myeloid leukemia ; AML ; bone marrow ; cancer ; cardiomyopathy ; cell ; compound ; decarboxylation ; dehydrogenase ; enzyme ; gene ; inherited ; leukemia ; mitochondria ; molecule ; mutation ; myeloid ; oxygen ; protein ; reactive oxygen species ; toxic
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.