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Genetics Home Reference: your guide to understanding genetic conditions
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UBE3A

Reviewed October 2011

What is the official name of the UBE3A gene?

The official name of this gene is “ubiquitin protein ligase E3A.”

UBE3A is the gene's official symbol. The UBE3A gene is also known by other names, listed below.

What is the normal function of the UBE3A gene?

The UBE3A gene provides instructions for making a protein called ubiquitin protein ligase E3A. Ubiquitin protein ligases are enzymes that target other proteins to be broken down (degraded) within cells. These enzymes attach a small protein called ubiquitin to proteins that should be degraded. Cellular structures called proteasomes recognize and digest these ubiquitin-tagged proteins. Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells.

Studies suggest that ubiquitin protein ligase E3A plays a critical role in the normal development and function of the nervous system. However, its exact role in nervous system cells is unclear.

People normally inherit two copies of the UBE3A gene, one from each parent. Both copies of the gene are turned on (active) in most of the body's tissues. In certain areas of the brain, however, only the copy inherited from a person's mother (the maternal copy) is active. This parent-specific gene activation results from a phenomenon known as genomic imprinting.

How are changes in the UBE3A gene related to health conditions?

Angelman syndrome - caused by mutations in the UBE3A gene

A loss of UBE3A gene function in the brain likely causes many of the characteristic features of Angelman syndrome, a complex genetic disorder that primarily affects the nervous system. This loss of function results from a chromosomal change or gene mutation that affects the maternal copy of the gene.

Several different genetic mechanisms can turn off (inactivate) or delete the UBE3A gene. Most cases of Angelman syndrome (about 70 percent) occur when a segment of the maternal chromosome 15 containing this gene is deleted. In another 11 percent of cases, Angelman syndrome results from mutations within the UBE3A gene itself. Most of these mutations lead to the production of an abnormally short, nonfunctional version of ubiquitin protein ligase E3A. Because the copy of the gene inherited from a person's father (the paternal copy) is normally inactive in some areas of the brain, loss of the maternal copy prevents any of the enzyme from being produced in these brain regions. This lack of enzyme function likely causes the major signs and symptoms of Angelman syndrome.

Other abnormalities involving the region of chromosome 15 that contains the UBE3A gene can also cause Angelman syndrome. These chromosomal changes include rearrangements (translocations) of genetic material or a defect in the region of DNA that controls activation of the UBE3A gene. Like mutations within the gene, these chromosomal changes prevent any functional ubiquitin protein ligase E3A from being produced in certain parts of the brain.

Where is the UBE3A gene located?

Cytogenetic Location: 15q11.2

Molecular Location on chromosome 15: base pairs 25,337,244 to 25,439,042

The UBE3A gene is located on the long (q) arm of chromosome 15 at position 11.2.

The UBE3A gene is located on the long (q) arm of chromosome 15 at position 11.2.

More precisely, the UBE3A gene is located from base pair 25,337,244 to base pair 25,439,042 on chromosome 15.

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 UBE3A?

You and your healthcare professional may find the following resources about UBE3A 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 UBE3A gene or gene products?

  • ANCR
  • CTCL tumor antigen se37-2
  • E6-AP
  • E6AP ubiquitin-protein ligase
  • EPVE6AP
  • HPVE6A
  • human papilloma virus E6-associated protein
  • oncogenic protein-associated protein E6-AP
  • UBE3A_HUMAN
  • ubiquitin protein ligase E3A (human papilloma virus E6-associated protein, Angelman syndrome)

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 UBE3A?

centrosome ; chromosome ; degradation ; DNA ; enzyme ; gene ; imprinting ; inherit ; inherited ; ligase ; maternal ; mutation ; nervous system ; papilloma ; protein ; syndrome ; tumor ; ubiquitin ; virus

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

References

  • Bittel DC, Kibiryeva N, Talebizadeh Z, Driscoll DJ, Butler MG. Microarray analysis of gene/transcript expression in Angelman syndrome: deletion versus UPD. Genomics. 2005 Jan;85(1):85-91. (http://www.ncbi.nlm.nih.gov/pubmed/15607424?dopt=Abstract)
  • Camprubí C, Guitart M, Gabau E, Coll MD, Villatoro S, Oltra S, Roselló M, Ferrer I, Monfort S, Orellana C, Martínez F. Novel UBE3A mutations causing Angelman syndrome: different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions. Am J Med Genet A. 2009 Mar;149A(3):343-8. doi: 10.1002/ajmg.a.32659. (http://www.ncbi.nlm.nih.gov/pubmed/19213023?dopt=Abstract)
  • Clayton-Smith J, Laan L. Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet. 2003 Feb;40(2):87-95. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12566516?dopt=Abstract)
  • Fang P, Lev-Lehman E, Tsai TF, Matsuura T, Benton CS, Sutcliffe JS, Christian SL, Kubota T, Halley DJ, Meijers-Heijboer H, Langlois S, Graham JM Jr, Beuten J, Willems PJ, Ledbetter DH, Beaudet AL. The spectrum of mutations in UBE3A causing Angelman syndrome. Hum Mol Genet. 1999 Jan;8(1):129-35. (http://www.ncbi.nlm.nih.gov/pubmed/9887341?dopt=Abstract)
  • Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Kim TK, Griffith EC, Waldon Z, Maehr R, Ploegh HL, Chowdhury S, Worley PF, Steen J, Greenberg ME. The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell. 2010 Mar 5;140(5):704-16. doi: 10.1016/j.cell.2010.01.026. (http://www.ncbi.nlm.nih.gov/pubmed/20211139?dopt=Abstract)
  • Lalande M, Calciano MA. Molecular epigenetics of Angelman syndrome. Cell Mol Life Sci. 2007 Apr;64(7-8):947-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17347796?dopt=Abstract)
  • Matentzoglu K, Scheffner M. Ubiquitin ligase E6-AP and its role in human disease. Biochem Soc Trans. 2008 Oct;36(Pt 5):797-801. doi: 10.1042/BST0360797. (http://www.ncbi.nlm.nih.gov/pubmed/18793139?dopt=Abstract)
  • Moncla A, Malzac P, Livet MO, Voelckel MA, Mancini J, Delaroziere JC, Philip N, Mattei JF. Angelman syndrome resulting from UBE3A mutations in 14 patients from eight families: clinical manifestations and genetic counselling. J Med Genet. 1999 Jul;36(7):554-60. (http://www.ncbi.nlm.nih.gov/pubmed/10424818?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7337)
  • Singhmar P, Kumar A. Angelman syndrome protein UBE3A interacts with primary microcephaly protein ASPM, localizes to centrosomes and regulates chromosome segregation. PLoS One. 2011;6(5):e20397. doi: 10.1371/journal.pone.0020397. Epub 2011 May 25. (http://www.ncbi.nlm.nih.gov/pubmed/21633703?dopt=Abstract)
  • Tan WH, Bacino CA, Skinner SA, Anselm I, Barbieri-Welge R, Bauer-Carlin A, Beaudet AL, Bichell TJ, Gentile JK, Glaze DG, Horowitz LT, Kothare SV, Lee HS, Nespeca MP, Peters SU, Sahoo T, Sarco D, Waisbren SE, Bird LM. Angelman syndrome: Mutations influence features in early childhood. Am J Med Genet A. 2011 Jan;155A(1):81-90. doi: 10.1002/ajmg.a.33775. (http://www.ncbi.nlm.nih.gov/pubmed/21204213?dopt=Abstract)

 

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: March 2, 2015