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L2HGDH gene

L-2-hydroxyglutarate dehydrogenase

Normal Function

The L2HGDH gene provides instructions for making an enzyme called L-2-hydroxyglutarate dehydrogenase. 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, L-2-hydroxyglutarate dehydrogenase converts a compound called L-2-hydroxyglutarate to another compound called 2-ketoglutarate. A series of additional enzymes further process 2-ketoglutarate to produce energy.

Health Conditions Related to Genetic Changes

2-hydroxyglutaric aciduria

Researchers have identified more than 70 mutations in the L2HGDH gene that cause a type of 2-hydroxyglutaric aciduria known as L-2-hydroxyglutaric aciduria (L-2-HGA). This condition has a variety of signs and symptoms that result from progressive damage to the brain beginning early in life.

Some L2HGDH gene mutations change single protein building blocks (amino acids) in the L-2-hydroxyglutarate dehydrogenase enzyme, which likely impairs its function. Other mutations insert or delete genetic material in the gene or lead to the production of an abnormally short, nonfunctional version of the enzyme. With a shortage of functional enzyme, L-2-hydroxyglutarate is not broken down but instead builds up 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 L-2-HGA primarily involve the brain.

More About This Health Condition

Other Names for This Gene

  • 2-hydroxyglutarate dehydrogenase
  • alpha-hydroxyglutarate oxidoreductase
  • alpha-ketoglutarate reductase
  • C14orf160
  • duranin
  • FLJ12618
  • L-alpha-hydroxyglutarate dehydrogenase

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases


  • 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. Citation on PubMed or Free article on PubMed Central
  • Rzem R, Van Schaftingen E, Veiga-da-Cunha M. The gene mutated in l-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase. Biochimie. 2006 Jan;88(1):113-6. doi: 10.1016/j.biochi.2005.06.005. Epub 2005 Jun 23. Citation on PubMed
  • Steenweg ME, Jakobs C, Errami A, van Dooren SJ, Adeva Bartolome MT, Aerssens P, Augoustides-Savvapoulou P, Baric I, Baumann M, Bonafe L, Chabrol B, Clarke JT, Clayton P, Coker M, Cooper S, Falik-Zaccai T, Gorman M, Hahn A, Hasanoglu A, King MD, de Klerk HB, Korman SH, Lee C, Meldgaard Lund A, Mejaski-Bosnjak V, Pascual-Castroviejo I, Raadhyaksha A, Rootwelt T, Roubertie A, Ruiz-Falco ML, Scalais E, Schimmel U, Seijo-Martinez M, Suri M, Sykut-Cegielska J, Trefz FK, Uziel G, Valayannopoulos V, Vianey-Saban C, Vlaho S, Vodopiutz J, Wajner M, Walter J, Walter-Derbort C, Yapici Z, Zafeiriou DI, Spreeuwenberg MD, Celli J, den Dunnen JT, van der Knaap MS, Salomons GS. An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study. Hum Mutat. 2010 Apr;31(4):380-90. doi: 10.1002/humu.21197. Citation on PubMed
  • Topcu M, Aydin OF, Yalcinkaya C, Haliloglu G, Aysun S, Anlar B, Topaloglu H, Turanli G, Yalnizoglu D, Kesimer M, Coskun T. L-2-hydroxyglutaric aciduria: a report of 29 patients. Turk J Pediatr. 2005 Jan-Mar;47(1):1-7. Citation on PubMed
  • Topcu M, Jobard F, Halliez S, Coskun T, Yalcinkayal C, Gerceker FO, Wanders RJ, Prud'homme JF, Lathrop M, Ozguc M, Fischer J. L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1. Hum Mol Genet. 2004 Nov 15;13(22):2803-11. doi: 10.1093/hmg/ddh300. Epub 2004 Sep 22. Citation on PubMed
  • Vilarinho L, Tafulo S, Sibilio M, Kok F, Fontana F, Diogo L, Venancio M, Ferreira M, Nogueira C, Valongo C, Parenti G, Amorim A, Azevedo L. Identification of novel L2HGDH gene mutations and update of the pathological spectrum. J Hum Genet. 2010 Jan;55(1):55-8. doi: 10.1038/jhg.2009.110. Epub 2009 Nov 13. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.