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Genetics Home Reference: your guide to understanding genetic conditions
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SDHA

Reviewed October 2011

What is the official name of the SDHA gene?

The official name of this gene is “succinate dehydrogenase complex, subunit A, flavoprotein (Fp).”

SDHA is the gene's official symbol. The SDHA gene is also known by other names, listed below.

What is the normal function of the SDHA gene?

The SDHA gene provides instructions for making one of four parts (subunits) of the succinate dehydrogenase (SDH) enzyme. The SDH enzyme plays a critical role in mitochondria, which are structures inside cells that convert the energy from food into a form that cells can use.

Within mitochondria, the SDH enzyme links two important pathways in energy conversion: the citric acid cycle (or Krebs cycle) and oxidative phosphorylation. As part of the citric acid cycle, the SDH enzyme converts a compound called succinate to another compound called fumarate. Negatively charged particles called electrons are released during this reaction. The SDHA protein is the active subunit of the enzyme that performs the conversion of succinate, and it also helps transfer electrons to the oxidative phosphorylation pathway. In oxidative phosphorylation, the electrons help create an electrical charge that provides energy for the production of adenosine triphosphate (ATP), the cell's main energy source.

Succinate, the compound on which the SDH enzyme acts, is an oxygen sensor in the cell and can help turn on specific pathways that stimulate cells to grow in a low-oxygen environment (hypoxia). In particular, succinate stabilizes a protein called hypoxia-inducible factor (HIF) by preventing a reaction that would allow HIF to be broken down. HIF controls several important genes involved in cell division and the formation of new blood vessels in a hypoxic environment.

The SDHA gene is a tumor suppressor gene, which means it prevents cells from growing and dividing in an uncontrolled way.

Does the SDHA gene share characteristics with other genes?

The SDHA gene belongs to a family of genes called mitochondrial respiratory chain complex (mitochondrial respiratory chain complex).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

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

nonsyndromic paraganglioma - increased risk from variations of the SDHA gene

At least three mutations in the SDHA gene have been identified in people with paraganglioma or pheochromocytoma (a type of paraganglioma), which are noncancerous (benign) tumors associated with the nervous system. SDHA gene mutations are seen most commonly in people with paraganglioma, but they have been found in people with pheochromocytoma. Specifically, SDHA gene mutations are associated with nonsyndromic paraganglioma or pheochromocytoma, which means the tumors are not part of an inherited syndrome.

A single mutation in the SDHA gene increases the risk that an individual will develop the condition. However, an additional mutation that deletes the normal copy of the gene is needed to cause tumor formation. This second mutation, called a somatic mutation, is acquired during a person's lifetime and is present only in tumor cells.

The SDHA gene mutations associated with nonsyndromic paraganglioma or pheochromocytoma change single protein building blocks (amino acids) in the SDHA protein sequence or result in a shortened protein. As a result, there is little or no SDH enzyme activity. Because the mutated SDH enzyme cannot convert succinate to fumarate, succinate accumulates in the cell. The excess succinate abnormally stabilizes HIF, which also builds up in cells. Excess HIF stimulates cells to divide and triggers the production of blood vessels when they are not needed. Rapid and uncontrolled cell division, along with the formation of new blood vessels, can lead to the development of tumors.

other disorders - caused by mutations in the SDHA gene

Mutations in the SDHA gene have been identified in a small number of people with Leigh syndrome, a progressive brain disorder that typically appears in infancy or early childhood. Affected children may experience vomiting, seizures, delayed development, muscle weakness, and problems with movement. Heart disease, kidney problems, and difficulty breathing can also occur in people with this disorder.

The SDHA gene mutations responsible for Leigh syndrome change single amino acids in the SDHA protein or result in an abnormally short protein. These genetic changes disrupt the activity of the SDH enzyme, impairing the ability of mitochondria to produce energy. It is not known, however, how mutations in the SDHA gene are related to the specific features of Leigh syndrome.

Where is the SDHA gene located?

Cytogenetic Location: 5p15

Molecular Location on chromosome 5: base pairs 218,222 to 256,699

The SDHA gene is located on the short (p) arm of chromosome 5 at position 15.

The SDHA gene is located on the short (p) arm of chromosome 5 at position 15.

More precisely, the SDHA gene is located from base pair 218,222 to base pair 256,699 on chromosome 5.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about SDHA?

You and your healthcare professional may find the following resources about SDHA 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 SDHA gene or gene products?

  • CMD1GG
  • DHSA_HUMAN
  • flavoprotein subunit of complex II
  • FP
  • SDH1
  • SDH2
  • SDHF
  • succinate dehydrogenase complex flavoprotein subunit
  • succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding SDHA?

acids ; adenosine triphosphate ; ATP ; benign ; cell ; cell division ; charged particles ; compound ; dehydrogenase ; enzyme ; gastrointestinal ; gene ; hypoxia ; hypoxic ; inherited ; kidney ; mitochondria ; mutation ; nervous system ; oxidative phosphorylation ; oxygen ; pheochromocytoma ; phosphorylation ; protein ; protein sequence ; somatic mutation ; subunit ; syndrome ; tumor ; tumor suppressor gene ; ubiquinone

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Burnichon N, Brière JJ, Libé R, Vescovo L, Rivière J, Tissier F, Jouanno E, Jeunemaitre X, Bénit P, Tzagoloff A, Rustin P, Bertherat J, Favier J, Gimenez-Roqueplo AP. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010 Aug 1;19(15):3011-20. doi: 10.1093/hmg/ddq206. Epub 2010 May 18. (http://www.ncbi.nlm.nih.gov/pubmed/20484225?dopt=Abstract)
  • Horváth R, Abicht A, Holinski-Feder E, Laner A, Gempel K, Prokisch H, Lochmüller H, Klopstock T, Jaksch M. Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA). J Neurol Neurosurg Psychiatry. 2006 Jan;77(1):74-6. (http://www.ncbi.nlm.nih.gov/pubmed/16361598?dopt=Abstract)
  • Korpershoek E, Favier J, Gaal J, Burnichon N, van Gessel B, Oudijk L, Badoual C, Gadessaud N, Venisse A, Bayley JP, van Dooren MF, de Herder WW, Tissier F, Plouin PF, van Nederveen FH, Dinjens WN, Gimenez-Roqueplo AP, de Krijger RR. SDHA immunohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas. J Clin Endocrinol Metab. 2011 Sep;96(9):E1472-6. doi: 10.1210/jc.2011-1043. Epub 2011 Jul 13. (http://www.ncbi.nlm.nih.gov/pubmed/21752896?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6389)
  • Opocher G, Schiavi F. Genetics of pheochromocytomas and paragangliomas. Best Pract Res Clin Endocrinol Metab. 2010 Dec;24(6):943-56. doi: 10.1016/j.beem.2010.05.001. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21115163?dopt=Abstract)
  • Parfait B, Chretien D, Rötig A, Marsac C, Munnich A, Rustin P. Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. Hum Genet. 2000 Feb;106(2):236-43. (http://www.ncbi.nlm.nih.gov/pubmed/10746566?dopt=Abstract)
  • Qin Y, Buddavarapu K, Dahia PL. Pheochromocytomas: from genetic diversity to new paradigms. Horm Metab Res. 2009 Sep;41(9):664-71. doi: 10.1055/s-0029-1215590. Epub 2009 Apr 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19391076?dopt=Abstract)
  • OMIM: SUCCINATE DEHYDROGENASE COMPLEX, SUBUNIT A, FLAVOPROTEIN (http://omim.org/entry/600857)

 

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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2011
Published: December 22, 2014