IDH1 gene

The IDH1 gene encodes an enzyme critical for cellular metabolism and protection against oxidative stress, with mutations often driving tumor formation and specific bone and blood disorders.

Normal Function

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) and in cellular structures called peroxisomes. In both locations, 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 the breakdown of fats for energy and protects cells from potentially harmful molecules called reactive oxygen species.

Health Conditions Related to Genetic Changes

Maffucci syndrome

Mutations in the IDH1 gene can cause Maffucci syndrome, a disorder characterized by multiple enchondromas (benign cartilage growths in bones) and hemangiomas (abnormal blood vessel growths in the skin). These mutations are somatic, meaning they occur during a person's lifetime and are not inherited. They result in mosaicism, where only some cells carry the mutation. These are gain-of-function mutations that cause the enzyme to produce D-2-hydroxyglutarate instead of its usual product.

Ollier disease

Mutations in the IDH1 gene also cause Ollier disease, a disorder similar to Maffucci syndrome but without the blood vessel abnormalities. Like Maffucci syndrome, these are somatic gain-of-function mutations resulting in mosaicism.

Cytogenetically normal acute myeloid leukemia

Mutations in the IDH1 gene have been identified in about 16 percent of people with cytogenetically normal acute myeloid leukemia (CN-AML). These somatic mutations change a single amino acid in the isocitrate dehydrogenase 1 enzyme. The resulting gain-of-function leads to the production of D-2-hydroxyglutarate, which may interfere with cell fate determination, causing immature blood cells to divide uncontrollably.

Other cancers

Somatic mutations in the IDH1 gene have been associated with other forms of cancer, including brain tumors called gliomas and bone tumors known as chondrosarcomas. These gain-of-function mutations lead to the abnormal production of D-2-hydroxyglutarate, which likely blocks the maturation of cells, resulting in the overproduction of immature cells and tumor formation.