PAX3

The PAX3 gene belongs to a family of genes that plays a critical role in the formation of tissues and organs during embryonic development. The PAX gene family is also important for maintaining the normal function of certain cells after birth. To carry out these roles, the proteins made by the PAX gene family bind to specific areas of DNA and regulate the activity of other genes. On the basis of this action, PAX proteins are called transcription factors.

During embryonic development, the PAX3 gene is active in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo and give rise to many tissues such as limb muscles, bones in the face and skull (craniofacial bones), certain nerve tissue, and pigment-producing cells called melanocytes. Melanocytes produce the pigment melanin, which contributes to hair, eye, and skin color, and they are also found in certain regions of the brain and inner ear.

Waardenburg syndrome - caused by mutations in the PAX3 gene

Several PAX3 mutations have been identified in people with Waardenburg syndrome, types I and III. These mutations change the chemical building blocks (amino acids) that make up the PAX3 protein or prematurely stop production of the protein. Researchers believe that all PAX3 mutations have the same effect: destroying the ability of the PAX3 protein to bind to DNA and regulate the activity of other genes (such as MITF). As a result, melanocytes do not develop in certain areas of the skin, hair, eyes, and inner ear, leading to hearing loss and the patchy loss of pigmentation that are characteristic features of Waardenburg syndrome. Additionally, loss of PAX3 protein function disrupts development of craniofacial bones and certain muscles, producing the limb and facial features that are unique to Waardenburg syndrome, types I and III.

cancers - associated with the PAX3 gene

Alterations in the activity of the PAX3 gene are associated with some cases of cancer of muscle tissue (alveolar rhabdomyosarcoma) that occur mainly in adolescents and young adults. Gene activity is altered when the PAX3 gene on chromosome 2 is fused with the FOXO1A gene (also called FKHR) on chromosome 13. This fusion event occurs when segments of chromosomes are rearranged in certain precursor muscle cells. The fused PAX3-FOXO1A gene may enhance changes that can lead to cancer, such as uncontrolled cell division and cell growth.

other disorders - caused by mutations in the PAX3 gene

One PAX3 mutation has been identified in individuals with a condition called craniofacial-deafness-hand syndrome. This condition is characterized by distinct facial features such as widely spaced eyes (hypertelorism) and a small nose, profound hearing loss, and hand abnormalities that affect the fingers and wrist. The mutation replaces the amino acid aspartic acid with lysine at position 47 in the PAX3 protein (also written as Asp47Lys). This mutation appears to drastically affect the ability of the PAX3 protein to bind to DNA. As a result, the PAX3 protein does not function properly in neural crest cells, disrupting the development of craniofacial bones, the inner ear, and limb muscles.

2q35-q37

The PAX3 gene is located on the long (q) arm of chromosome 2 between positions 35 and 37.

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

You and your healthcare professional may find the following resources about PAX3 helpful.

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals

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

• PubMed - Recent literature
• OMIM - Genetic disorder catalog (3 links)
• Research Resources - Tools for researchers (3 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

adolescent ; amino acid ; cancer ; cell division ; chromosome ; craniofacial ; DNA ; domain ; embryo ; gene ; hypertelorism ; melanin ; melanocytes ; mutation ; neural crest cell ; pigment ; pigmentation ; protein ; rhabdomyosarcoma ; transcription ; transcription factor

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