MITF

The MITF gene provides instructions for making a protein called microphthalmia-associated transcription factor. The MITF gene belongs to a family of genes that play a role in the development, survival, and function of several types of cells. To carry out this role, proteins made by this gene family bind to specific areas of DNA and regulate the activity of other genes. On the basis of this action, the proteins are called transcription factors.

To function as a transcription factor, the MITF protein has a particular structure with three critically important regions. One region, known as the basic motif, is the part of the protein that binds to specific areas of DNA. The other critical regions, called the helix-loop-helix motif and the leucine-zipper motif, allow the MITF protein to couple with itself or another protein from the same gene family. This coupling process produces the two-protein unit (dimer) that functions as a transcription factor.

Through its role as a transcription factor, the MITF protein controls the development and survival of pigment-producing cells called melanocytes. Within these cells, the MITF protein also controls production of the pigment melanin, which contributes to hair, eye, and skin color. Melanocytes are also found in the inner ear and play an important role in hearing. Additionally, the MITF protein regulates the development of specialized cells in the eye called retinal pigment epithelial cells. These cells nourish the retina, the part of the eye that detects light and color. Some research indicates that the MITF protein also regulates the development of cells that break down and remove bone (osteoclasts) and cells that play a role in allergic reactions (mast cells).

Waardenburg syndrome - caused by mutations in the MITF gene

MITF mutations have been identified in some people with Waardenburg syndrome, type II. Some of these mutations change the chemical building blocks (amino acids) that make up the MITF protein, which alters the helix-loop-helix or leucine-zipper motif. Other mutations shorten the MITF protein by prematurely stopping its production. Researchers believe that both types of mutations disrupt the formation of dimers. Although some functional dimers are produced to serve as transcription factors, the amount is insufficient for full development of melanocytes. As a result, there is a shortage of melanocytes 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.

other disorders - caused by mutations in the MITF gene

MITF mutations also cause Tietz syndrome, which is characterized by profound hearing loss from birth, fair skin, and light-colored hair. The mutations either delete or change a single amino acid in the basic motif region of the MITF protein. As a result, the altered protein cannot bind to DNA, which affects the development of melanocytes and melanin production. The absence or reduced number of melanocytes in the inner ear leads to hearing loss. Decreased melanin production (hypopigmentation) accounts for the light skin and hair color that are characteristic of Tietz syndrome.

3p14.2-p14.1

The MITF gene is located on the short (p) arm of chromosome 3 between positions 14.2 and 14.1.

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

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

• 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 (2 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

amino acid ; critical region ; dimer ; DNA ; gene ; homologs ; hypopigmentation ; mast cells ; melanin ; melanocytes ; microphthalmia ; motif ; mutation ; osteoclast ; pigment ; pigmentation ; protein ; retina ; transcription ; transcription factor

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