AR

The AR gene provides instruction for making a protein called an androgen receptor. Androgens are hormones (such as testosterone) that are important for normal male sexual development before birth and during puberty. Androgen receptors allow the body to respond appropriately to these hormones. The receptors are present in many of the body's tissues, where they are activated by binding to androgens. The active androgen-receptor complex binds to DNA and regulates the activity of androgen-responsive genes. By turning the genes on or off as necessary, the androgen receptor helps direct the development of male sexual characteristics.

In one region of the AR gene, a DNA segment known as CAG is repeated a number of times. This CAG segment is called a triplet or trinucleotide repeat. In most people, the number of CAG repeats ranges from fewer than 10 to about 36. 

androgen insensitivity syndrome - caused by mutations in the AR gene

More than 300 different mutations in the AR gene have been identified in people with androgen insensitivity syndrome (a condition that affects male sexual development before birth and during puberty). Most of these mutations are changes in single base pairs (the building blocks of DNA). Other mutations insert or delete multiple DNA base pairs in the gene or affect how the gene is processed into a protein. Changes in the AR gene can lead to an abnormally short protein or prevent the receptor from binding to androgens or to DNA. As a result, cells are less responsive to androgens or unable to use these hormones at all.

Mutations that completely eliminate the function of the androgen receptor cause complete androgen insensitivity syndrome. Genetic changes that reduce but do not eliminate the receptor's activity cause partial or mild androgen insensitivity syndrome.

spinal and bulbar muscular atrophy - caused by mutations in the AR gene

A particular type of mutation in the AR gene causes spinal and bulbar muscular atrophy. A DNA segment called a CAG triplet repeat is abnormally expanded within the AR gene. Normally, this segment is repeated about 10 to 36 times within the gene; however, in people with spinal and bulbar muscular atrophy, the CAG segment is repeated from 38 to more than 60 times. The extended CAG region changes the structure of the androgen receptor protein, which leads to the gradual loss of nerve cells in the brain and spinal cord that control muscle movement. It is not yet clearly understood how this mutation disrupts nerve cells. Researchers believe that a fragment of the androgen receptor protein containing the CAG repeats may accumulate over time in nerve cells and interfere with normal cell functions.

breast cancer - associated with the AR gene

Some recent studies have suggested that a long CAG repeat region in the AR gene is associated with an increased risk of breast cancer in women. Other studies, however, have not shown a correlation between the length of the CAG repeat region and the risk of breast cancer.

other cancers - associated with the AR gene

More than 85 mutations in the AR gene have been associated with prostate cancer. Some studies have shown an increased risk of prostate cancer in men with a short CAG repeat region; however, other studies did not find this connection. Researchers also believe that extra copies of the gene in cancer cells may be associated with the progression of prostate cancers.

Recently, research studies have also suggested that a larger CAG repeat region may increase the risk of endometrial cancer in women.

Xq11.2-q12

The AR gene is located on the long (q) arm of chromosome X between positions 11.2 and 12.

See How do geneticists indicate the location of a gene? in the Handbook.

You and your healthcare professional may find the following resources about AR helpful.

• Gene Reviews - Clinical summary (2 links)
• Gene Tests - DNA tests ordered by healthcare professionals (2 links)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

• PubMed - Recent literature
• OMIM - Genetic disorder catalog
• Research Resources - Tools for researchers (4 links)

See How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

• What is DNA?
• What is a gene?
• How does a gene make a protein?
• How can gene mutations cause disorders?

These links provide additional genetics resources that may be useful.

• Genetics education
• Human Genome Project
• Resources for Genetic Researchers

androgens ; atrophy ; base pair ; cancer ; DNA ; DNA base ; endometrial ; gene ; hormone ; mutation ; nerve cell ; progression ; prostate ; protein ; puberty ; receptor ; testosterone ; trinucleotide repeat

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.