UBE3A: How One Gene Mutation Causes A Particular Type Of Autism

Researchers have identified more than 1,000 gene mutations in people with autism, but until now, how any of these mutations increase autism was completely unclear. Autism researchers from the University of North Carolina (UNC) School of Medicine in Chapel Hill are reportedly the very first to figure out precisely how one of these 1,000 gene mutations leads to autism. It’s just one gene mutation, but it’s a big step for autism research.

“Genetic studies are showing that there will be about 1,000 genes linked to autism. This means you could mutate any one of them and get the disorder. We found how one of these mutations works,” Mark Zylka, associate professor of cell biology and physiology and senior author of the paper that was published in the journal Cell, said.

The mutation involves the gene UBE3A. Normally, the UBE3A gene can be turned on or off with a sort of regulatory switch. The key is the attachment of a phosphate molecule.

Mutations in the UBE3A gene destroy that switch so that enzyme UBE3A — encoded by the UBE3A gene — is hyperactive. The research team says that when it can’t be turned off, autism results.

Interestingly, parents of the children studied did not have any UBE3A mutations, but their children’s UBE3A gene was permanently switched on, Medical News Today reported. The researchers believe that hyperactivation of UBE3A is the cause of Dup15q-related autism.

According to Yahoo Health, the role of the UBE3A enzyme is to tag some proteins as waste to be destroyed. UBE3A is also known as the “Human Papillomavirus E6-associated protein” or “E6AP,” according to OMIM, because it was first identified as the tool used by HPV types 16 and 18 to destroy a tumor suppressor protein. Previous research indicated that “E6AP is absolutely required” for the growth of cervical cancer. In general though, UBE3A acts as a gatekeeper to protein degradation. When it’s switched on, proteins are degraded. When it’s off, they are not.

“It’s sort of like if you have garbage and you want to get rid of it, you can tag it with a flag for somebody to pick it up and throw it out. That’s essentially what UBE3A does,” Zylka said.

The research team studying autism and UBE3A believes that drugs already out there might be able to reduce the activity of UBE3A and treat autism.

“In fact,” Zylka said, “we tested known compounds and showed that two of them substantially reduced UBE3A activity in neurons.”

A drug called Rolipram was previously used to treat depression but was found to cause too many side effects to make it worth using for depression. According to the research team though, some Dup15q patients experience life-threatening seizures, so the benefits of the drug might just outweigh the risks.

In other autism related news, the Michigan Medical Marijuana Review Panel recently voted to recommend that children with autism have legal rights to consume marijuana medicinally.

[Photo via Pixabay]