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Genetics Home Reference: your guide to understanding genetic conditions
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SDHAF2

Reviewed June 2011

What is the official name of the SDHAF2 gene?

The official name of this gene is “succinate dehydrogenase complex assembly factor 2.”

SDHAF2 is the gene's official symbol. The SDHAF2 gene is also known by other names, listed below.

What is the normal function of the SDHAF2 gene?

The SDHAF2 gene provides instructions for making a protein that interacts with the succinate dehydrogenase (SDH) enzyme. The SDHAF2 protein helps a molecule called FAD attach to the SDH enzyme. FAD is called a cofactor because it helps the enzyme carry out its function. The FAD cofactor is required for SDH enzyme activity.

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.

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 SDHAF2 gene is a tumor suppressor, which means it prevents cells from growing and dividing in an uncontrolled way.

Does the SDHAF2 gene share characteristics with other genes?

The SDHAF2 gene belongs to a family of genes called mitochondrial respiratory chain complex assembly factors (mitochondrial respiratory chain complex assembly factors).

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 SDHAF2 gene related to health conditions?

hereditary paraganglioma-pheochromocytoma - increased risk from variations of the SDHAF2 gene

At least one mutation in the SDHAF2 gene has been identified in people with hereditary paraganglioma-pheochromocytoma type 2. People with this condition have paragangliomas, pheochromocytomas, or both. These noncancerous (benign) tumors are associated with the nervous system. The mutation replaces a protein building block (amino acid) in the SDHAF2 protein. Specifically, the amino acid glycine is replaced with the amino acid arginine at position 78 (written as Gly78Arg or G78R). The interaction between the mutated SDHAF2 protein and the SDH complex is impaired, and attachment of the FAD cofactor is decreased. As a result, the SDH enzyme is nonfunctional. Because the mutated SDH enzyme cannot convert succinate to fumarate, succinate accumulates in the cell. 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 in people with hereditary paraganglioma-pheochromocytoma.

Where is the SDHAF2 gene located?

Cytogenetic Location: 11q12.2

Molecular Location on chromosome 11: base pairs 61,430,124 to 61,446,766

The SDHAF2 gene is located on the long (q) arm of chromosome 11 at position 12.2.

The SDHAF2 gene is located on the long (q) arm of chromosome 11 at position 12.2.

More precisely, the SDHAF2 gene is located from base pair 61,430,124 to base pair 61,446,766 on chromosome 11.

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 SDHAF2?

You and your healthcare professional may find the following resources about SDHAF2 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 SDHAF2 gene or gene products?

  • C11orf79
  • FLJ20487
  • hSDH5
  • PGL2
  • SDH5
  • SDH assembly factor 2
  • SDHF2_HUMAN
  • succinate dehydrogenase assembly factor 2, mitochondrial
  • succinate dehydrogenase subunit 5, 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 SDHAF2?

amino acid ; arginine ; benign ; cell ; cell division ; cofactor ; compound ; dehydrogenase ; enzyme ; gene ; glycine ; hereditary ; hypoxia ; hypoxic ; mitochondria ; molecule ; mutation ; nervous system ; oxidative phosphorylation ; oxygen ; pheochromocytoma ; phosphorylation ; protein ; subunit ; tumor

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

References

  • Bayley JP, Kunst HP, Cascon A, Sampietro ML, Gaal J, Korpershoek E, Hinojar-Gutierrez A, Timmers HJ, Hoefsloot LH, Hermsen MA, Suárez C, Hussain AK, Vriends AH, Hes FJ, Jansen JC, Tops CM, Corssmit EP, de Knijff P, Lenders JW, Cremers CW, Devilee P, Dinjens WN, de Krijger RR, Robledo M. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. Lancet Oncol. 2010 Apr;11(4):366-72. doi: 10.1016/S1470-2045(10)70007-3. Epub 2010 Jan 11. (http://www.ncbi.nlm.nih.gov/pubmed/20071235?dopt=Abstract)
  • Hao HX, Khalimonchuk O, Schraders M, Dephoure N, Bayley JP, Kunst H, Devilee P, Cremers CW, Schiffman JD, Bentz BG, Gygi SP, Winge DR, Kremer H, Rutter J. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science. 2009 Aug 28;325(5944):1139-42. doi: 10.1126/science.1175689. Epub 2009 Jul 23. (http://www.ncbi.nlm.nih.gov/pubmed/19628817?dopt=Abstract)
  • Müller U. Pathological mechanisms and parent-of-origin effects in hereditary paraganglioma/pheochromocytoma (PGL/PCC). Neurogenetics. 2011 Aug;12(3):175-81. doi: 10.1007/s10048-011-0280-y. Epub 2011 Mar 9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21547462?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/54949)
  • Pasini B, Stratakis CA. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes. J Intern Med. 2009 Jul;266(1):19-42. doi: 10.1111/j.1365-2796.2009.02111.x. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19522823?dopt=Abstract)
  • Pollard PJ, Brière JJ, Alam NA, Barwell J, Barclay E, Wortham NC, Hunt T, Mitchell M, Olpin S, Moat SJ, Hargreaves IP, Heales SJ, Chung YL, Griffiths JR, Dalgleish A, McGrath JA, Gleeson MJ, Hodgson SV, Poulsom R, Rustin P, Tomlinson IP. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet. 2005 Aug 1;14(15):2231-9. Epub 2005 Jun 29. (http://www.ncbi.nlm.nih.gov/pubmed/15987702?dopt=Abstract)
  • Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB, Gottlieb E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005 Jan;7(1):77-85. (http://www.ncbi.nlm.nih.gov/pubmed/15652751?dopt=Abstract)
  • OMIM: SUCCINATE DEHYDROGENASE COMPLEX ASSEMBLY FACTOR 2 (http://omim.org/entry/613019)

 

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: June 2011
Published: November 24, 2014