More on the ATM gene

Genes in general

Genes carry all the instructions that living creatures need to grow in the first place and then for all the processes they undergo while living. A gene can be thought of as one individual instruction. Together all the genes which go to make up an individual are called its ‘genome’. The human genome contains an estimated 20,000 to 25,000 genes.

Each gene acts by producing a protein, which has a function in the cells of different parts of the body.

Genes are made up of segments of a chemical called DNA. They are packed together in structures called chromosomes and each gene has its place on one chromosome. Every individual has 23 pairs of chromosomes (a total of 46), one of each pair from their mother and one from their father. Therefore they have two copies of each gene, one from each parent.

The ATM gene

The gene we are interested in for A-T is situated on chromosome number 11. It has been given the name ATM gene, which stands for Ataxia-Telangiectasia Mutated. The ATM gene is a particularly big gene (for those interested in the details, it is made up of 66 exons and more than 150kb of DNA).

The gene was first identified in 1995 by a team in Israel led by Yossi Shiloh. However this identification was the result of close co-operation with other researchers, in particular Richard Gatti and Malcolm Taylor.

The ATM gene produces a protein which is also called ATM. This protein is produced in every cell in the body and has an important and complex role in the cell’s processes. 


A mutation on the gene takes the form of a change to the order of the units within the DNA. A particular section might get cut out, or it might be repeated or it might get jumbled up. Not all these changes  have an effect, as they may occur in a passage of DNA which is redundant (there is plenty of this) or it might not be sufficient to affect the role of the gene.

There are a number of different types of mutation, though the subject is too complex to cover in detail here. The majority of these mutations stop the process by which the ATM gene produces ATM protein in the middle. These are known as 'truncating mutations'and  produce no viable protein. These are the mutations that cause classic A-T.

However, there are a number of mutations that are of particular interest:

Nonsense mutations

In a nonsense mutation, a particular chemical group, also known as a 'stop-codon', which normally appears at the end of the gene and tells the protein-making process to stop, appears in the middle of the gene . It’s as if halfway through a recipe, we came to the words “the End”. The result is that the production of the protein stops in the middle, leaving an unfinished protein. This form of mutation is of interest because there appear to be certain drugs that can 'read across' this stop-codon and allow the protein to be finished. Researchers are trying to identify a drug that will do this for ATM.

Splice site mutations

This kind of mutation can in some cases allow a small amount of protein to be made. This is the case with one particular mutation,  known as ' ATM 5762ins137', which is particularly common in the population of the UK and Ireland, where it is found in around 10% of people with A-T. This mutation allows perhaps 4% of the normal production of ATM protein. While this is not enough to protect from A-T, it does result in a milder form of the condition.

Missense mutations

A missense mutation involves a small change to a single chemical group. This can sometimes result in the production of a protein which is very similar to the normal form and may function with some of the effect of the normal protein. Where this is the case, again it can result in a milder form of the condition.