UBE3A

The UBE3A gene provides instructions for making an enzyme called ubiquitin protein ligase E3A. This enzyme is involved in targeting proteins to be broken down (degraded) within cells. For example, the p53 protein, which controls cell growth and division, is one of the targets of ubiquitin protein ligase E3A. Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells.

Ubiquitin protein ligase 3A attaches a small protein called ubiquitin to proteins that should be degraded. Cellular structures called proteasomes recognize and digest proteins tagged with ubiquitin.

People normally inherit two copies of the UBE3A gene, one from each parent. Both copies of the gene are 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.

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 inactivate or delete the UBE3A gene. In some cases, Angelman syndrome results from mutations within the 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, a mutation in the remaining maternal copy prevents any of the enzyme from being produced in these brain regions. This loss of enzyme function likely causes the characteristic features of Angelman syndrome.

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