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The official name of this gene is “isocitrate dehydrogenase 1 (NADP+).”
IDH1 is the gene's official symbol. The IDH1 gene is also known by other names, listed below.
The IDH1 gene provides instructions for making an enzyme called isocitrate dehydrogenase 1. This enzyme is primarily found in the fluid-filled space inside cells (the cytoplasm). It is also found in cellular structures called peroxisomes, which are small sacs within cells that process many types of molecules. In both the cytoplasm and in peroxisomes, isocitrate dehydrogenase 1 converts a compound called isocitrate to another compound called 2-ketoglutarate. This reaction also produces a molecule called NADPH, which is necessary for many cellular processes. The NADPH produced from isocitrate dehydrogenase 1 is involved in the breakdown of fats for energy, and it also protects cells from potentially harmful molecules called reactive oxygen species.
Mutations in the IDH1 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. IDH1 gene mutations occur in about 16 percent of people with CN-AML.
The IDH1 gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. They change a single protein building block (amino acid) in the isocitrate dehydrogenase 1 enzyme, replacing the amino acid arginine at position 132 with another amino acid. The IDH1 gene mutations found in CN-AML prevent isocitrate dehydrogenase 1 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. 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 IDH1 gene mutations divide uncontrollably, leading to CN-AML.
Somatic mutations in the IDH1 gene have been associated with several other forms of cancer, including brain tumors called gliomas and bone tumors known as chondrosarcomas. Like the genetic changes that cause CN-AML (described above), the IDH1 gene mutations found in these cancers are gain-of-function mutations. These mutations alter the function of isocitrate dehydrogenase 1 such that it abnormally produces D-2-hydroxyglutarate. As in CN-AML, D-2-hydroxyglutarate likely blocks the maturation of cells, resulting in overproduction of immature cells and tumor formation. It is unclear why IDH1 gene mutations have been found in only these few types of cancer.
Some people with conditions known as Maffucci syndrome and Ollier disease have mutations in the IDH1 gene. These conditions are characterized by multiple noncancerous growths on the bones (endochondromas) in addition to other signs and symptoms. In these individuals, only a small number of the endochondromas have the mutated gene, and tissues in the rest of the body do not carry the mutation. In some people with Maffucci syndrome or Ollier disease, the endochondromas become cancerous chondrosarcomas. How IDH1 gene mutations contribute to the development of endochondromas in Maffucci syndrome and Ollier disease is unknown.
Cytogenetic Location: 2q33.3
Molecular Location on chromosome 2: base pairs 208,236,227 to 208,255,143
The IDH1 gene is located on the long (q) arm of chromosome 2 at position 33.3.
More precisely, the IDH1 gene is located from base pair 208,236,227 to base pair 208,255,143 on chromosome 2.
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 IDH1 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.
acute ; acute myeloid leukemia ; amino acid ; AML ; arginine ; breakdown ; cancer ; cell ; compound ; cytoplasm ; dehydrogenase ; enzyme ; gene ; inherited ; leukemia ; molecule ; mutation ; myeloid ; oxygen ; peroxisomes ; protein ; reactive oxygen species ; soluble ; syndrome ; tumor
You may find definitions for these and many other terms in the Genetics Home Reference 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.