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SLC25A1 gene

solute carrier family 25 member 1

Normal Function

The SLC25A1 gene provides instructions for making a protein that is found in mitochondria, which are the energy-producing centers in cells. The SLC25A1 protein transports a molecule called citrate out of mitochondria in exchange for another molecule called malate, which is transported in. Within mitochondria, both citrate and malate participate in reactions that produce energy for cell activities. Citrate is transported out of mitochondria because it also has important functions in other parts of the cell. In particular, citrate is involved in the production of fats (lipids) and the regulation of glycolysis, which is another critical energy-producing process within cells.

Health Conditions Related to Genetic Changes

2-hydroxyglutaric aciduria

At least 12 mutations in the SLC25A1 gene have been found to cause a form of 2-hydroxyglutaric aciduria called combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA). This condition causes severe brain abnormalities that become apparent in early infancy.

Each of the known SLC25A1 gene mutations greatly reduces the function of the SLC25A1 protein. As a result, citrate and malate cannot be transported into and out of mitochondria, which disrupts energy production within cells. Through processes that are not fully understood, the lack of citrate and malate transport allows other compounds to build up abnormally within cells. These compounds include D-2-hydroxyglutarate and L-2-hydroxyglutarate, which at high levels can damage cells and lead to cell death. Brain cells appear to be the most vulnerable to the toxic effects of these compounds, which may explain why the signs and symptoms of D,L-2-HGA primarily involve the brain. Researchers suspect that an imbalance of other molecules, particularly citrate, also contributes to the severe signs and symptoms of combined D,L-2-HGA

More About This Health Condition

Other Names for This Gene

  • citrate transport protein
  • CTP
  • D2L2AD
  • SEA
  • SLC20A3
  • solute carrier family 20 (mitochondrial citrate transporter), member 3
  • solute carrier family 25 (mitochondrial carrier; citrate transporter), member 1
  • tricarboxylate carrier protein
  • tricarboxylate transport protein, mitochondrial

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Gene and Variant Databases


  • Catalina-Rodriguez O, Kolukula VK, Tomita Y, Preet A, Palmieri F, Wellstein A, Byers S, Giaccia AJ, Glasgow E, Albanese C, Avantaggiati ML. The mitochondrial citrate transporter, CIC, is essential for mitochondrial homeostasis. Oncotarget. 2012 Oct;3(10):1220-35. doi: 10.18632/oncotarget.714. Citation on PubMed or Free article on PubMed Central
  • Iacobazzi V, Lauria G, Palmieri F. Organization and sequence of the human gene for the mitochondrial citrate transport protein. DNA Seq. 1997;7(3-4):127-39. doi: 10.3109/10425179709034029. Citation on PubMed
  • Nota B, Struys EA, Pop A, Jansen EE, Fernandez Ojeda MR, Kanhai WA, Kranendijk M, van Dooren SJ, Bevova MR, Sistermans EA, Nieuwint AW, Barth M, Ben-Omran T, Hoffmann GF, de Lonlay P, McDonald MT, Meberg A, Muntau AC, Nuoffer JM, Parini R, Read MH, Renneberg A, Santer R, Strahleck T, van Schaftingen E, van der Knaap MS, Jakobs C, Salomons GS. Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. Am J Hum Genet. 2013 Apr 4;92(4):627-31. doi: 10.1016/j.ajhg.2013.03.009. Citation on PubMed or Free article on PubMed Central
  • Palmieri F. The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol Aspects Med. 2013 Apr-Jun;34(2-3):465-84. doi: 10.1016/j.mam.2012.05.005. Epub 2012 Dec 23. 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.