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URL of this page: https://medlineplus.gov/genetics/gene/sucla2/

SUCLA2 gene

succinate-CoA ligase ADP-forming subunit beta

Normal Function

The SUCLA2 gene provides instructions for making one part (the beta subunit) of an enzyme called succinyl-CoA ligase. The body makes two slightly different versions of this enzyme. The version that contains the SUCLA2 beta subunit is most active in tissues that require a large amount of energy, such as the brain and muscles. The other version is more active in the liver and other tissues.

Succinyl-CoA ligase plays a critical role in mitochondria, which are the energy-producing centers inside the cell. This enzyme is 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

SUCLA2-related mitochondrial DNA depletion syndrome

Variants (also called mutations) in the SUCLA2 gene cause SUCLA2-related mtDNA depletion syndrome, an inherited disorder that affects the early development of the brain. SUCLA2 gene variants alter the structure of the beta subunit of succinyl-CoA ligase, reducing the enzyme's activity. 

A shortage (deficiency) of normal succinyl-CoA ligase leads to problems with the production and maintenance of mtDNA, particularly in the developing brain and muscles. A reduction in the amount of mtDNA (known as mtDNA depletion) impairs energy production within cells. These problems lead to weak muscle tone (hypotonia), delayed development, and the other characteristic features of SUCLA2-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

  • A-BETA
  • A-SCS
  • ATP-specific succinyl-CoA synthetase, beta subunit
  • SCS-betaA
  • succinate-CoA ligase beta subunit
  • succinate-CoA ligase, ADP-forming, beta subunit

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, Dionisi-Vici C, Steuerwald U, Lucioli S, Deodato F, Di Giandomenico S, Bertini E, Franke B, Kluijtmans LA, Meschini MC, Rizzo C, Piemonte F, Rodenburg R, Santer R, Santorelli FM, van Rooij A, Vermunt-de Koning D, Morava E, Wevers RA. SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Brain. 2007 Mar;130(Pt 3):862-74. doi: 10.1093/brain/awl389. Epub 2007 Feb 14. Citation on PubMed
  • 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
  • Chinnery PF. Mutations in SUCLA2: a tandem ride back to the Krebs cycle. Brain. 2007 Mar;130(Pt 3):606-9. doi: 10.1093/brain/awm023. No abstract available. Citation on PubMed
  • El-Hattab AW, Scaglia F. SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria. 2009 May 26 [updated 2023 Sep 28]. 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/NBK6803/ Citation on PubMed
  • Elpeleg O, Miller C, Hershkovitz E, Bitner-Glindzicz M, Bondi-Rubinstein G, Rahman S, Pagnamenta A, Eshhar S, Saada A. Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion. Am J Hum Genet. 2005 Jun;76(6):1081-6. doi: 10.1086/430843. Epub 2005 Apr 22. Citation on PubMed or Free article on PubMed Central
  • 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, Hansen FJ, Sorensen N, Duno M, Vissing J, Larsen PL, Faeroe O, Thorgrimsson S, Wibrand F, Christensen E, Schwartz M. Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations. Brain. 2007 Mar;130(Pt 3):853-61. doi: 10.1093/brain/awl383. Epub 2007 Feb 7. 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

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