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URL of this page: https://medlineplus.gov/genetics/gene/suclg1/

SUCLG1 gene

succinate-CoA ligase GDP/ADP-forming subunit alpha

Normal Function

The SUCLG1 gene provides instructions for making one part (the alpha subunit) of an enzyme called succinyl-CoA ligase. The alpha subunit is used to make two slightly different versions of this enzyme. One version is most active in tissues such as the brain and muscle that require a large amount of energy, while the other version is most active in tissues that require less energy.

Both versions of succinyl-CoA ligase play an important role in mitochondria, which are the energy-producing centers inside the cell. These enzymes are involved in a series of chemical reactions known as the citric acid cycle (or Krebs cycle). These reactions allow cells to use oxygen and produce energy.

Mitochondria each contain a small amount of DNA, known as mitochondrial DNA or mtDNA. Studies suggest that succinyl-CoA ligase interacts with another enzyme, called nucleoside diphosphate kinase, to produce and maintain the molecules that make up mtDNA. Having an adequate amount of mtDNA is essential for normal energy production within cells.

Health Conditions Related to Genetic Changes

SUCLG1-related mitochondrial DNA depletion syndrome

Variants (also called mutations) in the SUCLG1 gene cause SUCLG1-related mtDNA depletion syndrome, an inherited disorder that affects the early development of the brain. 

Most SUCLG1 gene variants change a single protein building block (amino acid) in the alpha subunit of succinyl-CoA ligase, which reduces but does not eliminate the activity of the enzyme. People with some enzyme activity typically have milder signs and symptoms than people with no enzyme activity.

A shortage (deficiency) of normal succinyl-CoA ligase leads to problems with the production and maintenance of mtDNA. A reduction in the amount of mtDNA (known as mtDNA depletion) impairs energy production in many of the body's cells and tissues and leads to the characteristic features of SUCLG1-related mtDNA depletion syndrome. 

More About This Health Condition

Leigh syndrome

MedlinePlus Genetics provides information about Leigh syndrome

More About This Health Condition

Other Names for This Gene

  • GALPHA
  • succinate-CoA ligase, ADP-forming, alpha subunit
  • succinate-CoA ligase, GDP-forming, alpha subunit
  • succinyl-CoA synthetase, alpha subunit
  • SUCLA1

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

References

  • Carrozzo R, Verrigni D, Rasmussen M, de Coo R, Amartino H, Bianchi M, Buhas D, Mesli S, Naess K, Born AP, Woldseth B, Prontera P, Batbayli M, Ravn K, Joensen F, Cordelli DM, Santorelli FM, Tulinius M, Darin N, Duno M, Jouvencel P, Burlina A, Stangoni G, Bertini E, Redonnet-Vernhet I, Wibrand F, Dionisi-Vici C, Uusimaa J, Vieira P, Osorio AN, McFarland R, Taylor RW, Holme E, Ostergaard E. Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients. J Inherit Metab Dis. 2016 Mar;39(2):243-52. doi: 10.1007/s10545-015-9894-9. Epub 2015 Oct 16. Citation on PubMed
  • El-Hattab AW, Scaglia F. SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria. 2017 Mar 30. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK425223/ Citation on PubMed
  • Kowluru A, Tannous M, Chen HQ. Localization and characterization of the mitochondrial isoform of the nucleoside diphosphate kinase in the pancreatic beta cell: evidence for its complexation with mitochondrial succinyl-CoA synthetase. Arch Biochem Biophys. 2002 Feb 15;398(2):160-9. doi: 10.1006/abbi.2001.2710. Citation on PubMed
  • Lambeth DO, Tews KN, Adkins S, Frohlich D, Milavetz BI. Expression of two succinyl-CoA synthetases with different nucleotide specificities in mammalian tissues. J Biol Chem. 2004 Aug 27;279(35):36621-4. doi: 10.1074/jbc.M406884200. Epub 2004 Jul 2. Citation on PubMed
  • Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, Wibrand F. Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. Am J Hum Genet. 2007 Aug;81(2):383-7. doi: 10.1086/519222. Epub 2007 Jun 4. Citation on PubMed or Free article on PubMed Central
  • Ostergaard E, Schwartz M, Batbayli M, Christensen E, Hjalmarson O, Kollberg G, Holme E. A novel missense mutation in SUCLG1 associated with mitochondrial DNA depletion, encephalomyopathic form, with methylmalonic aciduria. Eur J Pediatr. 2010 Feb;169(2):201-5. doi: 10.1007/s00431-009-1007-z. Epub 2009 Jun 14. Citation on PubMed
  • Ostergaard E. Disorders caused by deficiency of succinate-CoA ligase. J Inherit Metab Dis. 2008 Apr;31(2):226-9. doi: 10.1007/s10545-008-0828-7. Epub 2008 Apr 4. 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.