UBE3A & Mutation: How This One Gene Mutation Can Lead to Autism

November 2, 2015 | Abrams Nation

There are over one thousand different gene mutations that can lead to autism, and for a long time all researchers could do was catalog the mutations without knowing how they caused autism. Recently, a team of researchers at the University of North Carolina (UNC) School of Medicine in Chapel Hill discovered how a particular mutation leads to a kind of autism, which is a first in the field.

The UBE3A Gene and What It’s Supposed to Do

The UBE3A gene is found throughout the body. It’s role is to place a marker on proteins for degradation. This marker signals parts of the cell’s structure to digest and break down the protein. Protein degradation is a key part of cellular function and allows the cells to get rid of damaged or unnecessary proteins.

By getting rid of these unusable proteins, the cell can develop and function better. UBE3A in particular plays a vital role in the development of the brain, which is why a small mutation can have large consequences.

What Can Go Wrong with UBE3A?

The researchers at UNC found out that the UBE3A gene has a receptor for a phosphate molecule that can start or stop the function of the gene. Basically, the gene has an on/off switch. When a mutation damages this receptor, the gene cannot be turned off and develops hyperactivity. According to their research, this hyperactivity can cause types of autism.

Here’s another way to think about it: imagine someone with spray paint walking around a forest marking dead, dying, or rotting trees. Now imagine what would happen if that person kept spraying and marked a bunch of healthy trees. The lumberjacks would get pushed too hard and eventually would stop removing problem trees. As a result, there would be no room for new trees to grow.

That’s basically what happens with a mutated UBE3A. It becomes hyperactive, and the result is a decreased ability of the brain to make space for new synapses. The creation of synapses is crucial for learning, and research has shown that clearing out the old synapses is just as important.

How Does This Relate to Autism?

The researchers found that a mutated UBE3A is linked to Dup15q syndrome. The syndrome is cause by duplications or deletions in the q11.2-q13.1 area of chromosome 15, and the UBE3A gene is located right in that range. A hyperactive or mutated UBE3A gene may be the cause of some kinds of Dup15q syndrome.

What Does This Mean for Treatment?

The most exciting part about this research is that it opens up a path for treatment of this kind of autism. If the problem is due to a hyperactive UBE3A gene, then the answer is to limit the activity of the gene, similar to taking away the spray can from the person in the analogy above.

There are even some drugs currently on the market that have been shown to limit this activity. More studies needs to be done to isolate a viable treatment for UBE3A hyperactivity, but this discovery has given a clear path for treatment research.