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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed January 2014

What is the official name of the IDH2 gene?

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.

What is the normal function of the IDH2 gene?

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.

How are changes in the IDH2 gene related to health conditions?

2-hydroxyglutaric aciduria - caused by mutations in the IDH2 gene

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.

cytogenetically normal acute myeloid leukemia - associated with the IDH2 gene

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.

other cancers - associated with the IDH2 gene

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.

Where is the IDH2 gene located?

Cytogenetic Location: 15q26.1

Molecular Location on chromosome 15: base pairs 90,083,978 to 90,102,554

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

The IDH2 gene is located on the long (q) arm of chromosome 15 at position 26.1.

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 90,083,978 to base pair 90,102,554 on chromosome 15.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about IDH2?

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.

What other names do people use for the IDH2 gene or gene products?

  • D2HGA2
  • ICD-M
  • IDH
  • IDHM
  • IDP
  • IDPM
  • isocitrate dehydrogenase [NADP], mitochondrial
  • NADP(+)-specific ICDH
  • oxalosuccinate decarboxylase

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding IDH2?

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.


  • Kranendijk M, Struys EA, Salomons GS, Van der Knaap MS, Jakobs C. Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis. 2012 Jul;35(4):571-87. doi: 10.1007/s10545-012-9462-5. Epub 2012 Mar 6. Review. (
  • Kranendijk M, Struys EA, van Schaftingen E, Gibson KM, Kanhai WA, van der Knaap MS, Amiel J, Buist NR, Das AM, de Klerk JB, Feigenbaum AS, Grange DK, Hofstede FC, Holme E, Kirk EP, Korman SH, Morava E, Morris A, Smeitink J, Sukhai RN, Vallance H, Jakobs C, Salomons GS. IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. Science. 2010 Oct 15;330(6002):336. doi: 10.1126/science.1192632. Epub 2010 Sep 16. (
  • Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C, Cowley GS, Root DE, Ebert BL, Kaelin WG Jr. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science. 2013 Mar 29;339(6127):1621-5. doi: 10.1126/science.1231677. Epub 2013 Feb 7. (
  • Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, Wellen KE, O'Rourke DM, Berger SL, Chan TA, Levine RL, Mellinghoff IK, Thompson CB. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 2012 Feb 15;483(7390):474-8. doi: 10.1038/nature10860. (
  • NCBI Gene (
  • Reitman ZJ, Yan H. Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. J Natl Cancer Inst. 2010 Jul 7;102(13):932-41. doi: 10.1093/jnci/djq187. Epub 2010 May 31. Review. (
  • Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, Pardanani A, Pereira A, Finke C, Score J, Gangat N, Mannarelli C, Ketterling RP, Rotunno G, Knudson RA, Susini MC, Laborde RR, Spolverini A, Pancrazzi A, Pieri L, Manfredini R, Tagliafico E, Zini R, Jones A, Zoi K, Reiter A, Duncombe A, Pietra D, Rumi E, Cervantes F, Barosi G, Cazzola M, Cross NC, Tefferi A. Mutations and prognosis in primary myelofibrosis. Leukemia. 2013 Sep;27(9):1861-9. doi: 10.1038/leu.2013.119. Epub 2013 Apr 26. (
  • Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE, Rabinowitz JD, Carroll M, Su SM, Sharp KA, Levine RL, Thompson CB. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010 Mar 16;17(3):225-34. doi: 10.1016/j.ccr.2010.01.020. Epub 2010 Feb 18. (
  • Yang H, Ye D, Guan KL, Xiong Y. IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res. 2012 Oct 15;18(20):5562-71. doi: 10.1158/1078-0432.CCR-12-1773. Review. (
  • Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009 Feb 19;360(8):765-73. doi: 10.1056/NEJMoa0808710. (


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? ( in the Handbook.

Reviewed: January 2014
Published: February 8, 2016