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Genetics Home Reference: your guide to understanding genetic conditions
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MITF

Reviewed December 2015

What is the official name of the MITF gene?

The official name of this gene is “microphthalmia-associated transcription factor.”

MITF is the gene's official symbol. The MITF gene is also known by other names, listed below.

What is the normal function of the MITF gene?

The MITF gene provides instructions for making a protein called microphthalmia-associated transcription factor. This protein plays a role in the development, survival, and function of certain types of cells. To carry out this role, the protein attaches to specific areas of DNA and helps control the activity of particular genes. On the basis of this action, the protein is called a transcription factor.

Microphthalmia-associated transcription factor helps control the development and function of pigment-producing cells called melanocytes. Within these cells, this protein 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, microphthalmia-associated transcription factor 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 microphthalmia-associated transcription factor also regulates the development of cells that break down and remove bone (osteoclasts) and cells that play a role in allergic reactions (mast cells).

The structure of microphthalmia-associated transcription factor includes three critically important regions. Two of the regions, called the helix-loop-helix motif and the leucine-zipper motif, are critical for protein interactions. These motifs allow molecules of microphthalmia-associated transcription factor to interact with each other or with other proteins that have a similar structure, creating a two-protein unit (dimer) that functions as a transcription factor. The other region, known as the basic motif, binds to specific areas of DNA, allowing the dimer to control gene activity.

Does the MITF gene share characteristics with other genes?

The MITF gene belongs to a family of genes called bHLH (basic helix-loop-helix).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the MITF gene related to health conditions?

Tietz syndrome - caused by mutations in the MITF gene

At least two MITF gene mutations have been identified in people with Tietz syndrome, which is characterized by profound hearing loss from birth, fair skin, and light-colored hair. Researchers suggest that Tietz syndrome may be a severe form of Waardenburg syndrome (described below).

The MITF gene mutations that cause Tietz syndrome either delete or change a single protein building block (amino acid) in the basic motif region of the microphthalmia-associated transcription factor structure. Dimers incorporating the abnormal microphthalmia-associated transcription factor cannot be transported into the cell nucleus to bind with DNA. As a result, most of the dimers are unavailable to bind to DNA, which affects the development of melanocytes and the production of melanin. The resulting reduction or absence 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.

Waardenburg syndrome - caused by mutations in the MITF gene

More than 35 mutations in the MITF gene have been identified in people with Waardenburg syndrome, type II, a disorder that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes. Some MITF gene mutations change the amino acids used to make microphthalmia-associated transcription factor, which alters the helix-loop-helix or leucine-zipper motif. Other mutations result in an abnormally small version of microphthalmia-associated transcription factor. Researchers believe that both types of mutations disrupt the formation of dimers. Although some dimers are produced, 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. This shortage can lead to hearing loss and the patchy loss of pigmentation associated with Waardenburg syndrome.

cancers - associated with the MITF gene

MITF gene mutations have also been found in people with an aggressive form of skin cancer called melanoma. Most of these mutations are somatic, meaning that they occur during a person's lifetime and are present only in certain cells, in this case cells that give rise to the melanoma. Occasionally the mutation is inherited and is found in every cell of the body (known as a germline mutation). Some of the MITF gene mutations associated with melanoma increase cell growth and division (proliferation) directly. Other mutations have an indirect effect, increasing the activity (expression) of other genes involved in proliferation and resulting in the abnormal cell growth that occurs in melanoma.

Where is the MITF gene located?

Cytogenetic Location: 3p14.2-p14.1

Molecular Location on chromosome 3: base pairs 69,739,435 to 69,968,337

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/4286))

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

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

More precisely, the MITF gene is located from base pair 69,739,435 to base pair 69,968,337 on chromosome 3.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about MITF?

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

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

What other names do people use for the MITF gene or gene products?

  • homolog of mouse microphthalmia
  • MITF_HUMAN
  • WS2A

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding MITF?

acids ; amino acid ; cancer ; cell ; cell nucleus ; dimer ; DNA ; epithelial ; gene ; germline ; germline mutation ; hypopigmentation ; inherited ; leucine ; mast cells ; melanin ; melanocytes ; melanoma ; motif ; mutation ; nucleus ; pigment ; pigmentation ; proliferation ; protein ; retina ; syndrome ; transcription ; transcription factor

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

References

  • Amiel J, Watkin PM, Tassabehji M, Read AP, Winter RM. Mutation of the MITF gene in albinism-deafness syndrome (Tietz syndrome). Clin Dysmorphol. 1998 Jan;7(1):17-20. (http://www.ncbi.nlm.nih.gov/pubmed/9546825?dopt=Abstract)
  • Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M. Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Mol Genet. 2000 Aug 12;9(13):1907-17. (http://www.ncbi.nlm.nih.gov/pubmed/10942418?dopt=Abstract)
  • Grill C, Bergsteinsdóttir K, Ogmundsdóttir MH, Pogenberg V, Schepsky A, Wilmanns M, Pingault V, Steingrímsson E. MITF mutations associated with pigment deficiency syndromes and melanoma have different effects on protein function. Hum Mol Genet. 2013 Nov 1;22(21):4357-67. doi: 10.1093/hmg/ddt285. Epub 2013 Jun 20. (http://www.ncbi.nlm.nih.gov/pubmed/23787126?dopt=Abstract)
  • Izumi K, Kohta T, Kimura Y, Ishida S, Takahashi T, Ishiko A, Kosaki K. Tietz syndrome: unique phenotype specific to mutations of MITF nuclear localization signal. Clin Genet. 2008 Jul;74(1):93-5. doi: 10.1111/j.1399-0004.2008.01010.x. Epub 2008 May 28. (http://www.ncbi.nlm.nih.gov/pubmed/18510545?dopt=Abstract)
  • Léger S, Balguerie X, Goldenberg A, Drouin-Garraud V, Cabot A, Amstutz-Montadert I, Young P, Joly P, Bodereau V, Holder-Espinasse M, Jamieson RV, Krause A, Chen H, Baumann C, Nunes L, Dollfus H, Goossens M, Pingault V. Novel and recurrent non-truncating mutations of the MITF basic domain: genotypic and phenotypic variations in Waardenburg and Tietz syndromes. Eur J Hum Genet. 2012 May;20(5):584-7. doi: 10.1038/ejhg.2011.234. Epub 2012 Jan 18. (http://www.ncbi.nlm.nih.gov/pubmed/22258527?dopt=Abstract)
  • OMIM: MICROPHTHALMIA-ASSOCIATED TRANSCRIPTION FACTOR (http://omim.org/entry/156845)
  • Murakami H, Arnheiter H. Sumoylation modulates transcriptional activity of MITF in a promoter-specific manner. Pigment Cell Res. 2005 Aug;18(4):265-77. (http://www.ncbi.nlm.nih.gov/pubmed/16029420?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4286)
  • Potterf SB, Furumura M, Dunn KJ, Arnheiter H, Pavan WJ. Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3. Hum Genet. 2000 Jul;107(1):1-6. (http://www.ncbi.nlm.nih.gov/pubmed/10982026?dopt=Abstract)
  • Read AP. Waardenburg syndrome. Adv Otorhinolaryngol. 2000;56:32-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10868211?dopt=Abstract)
  • Smith SD, Kelley PM, Kenyon JB, Hoover D. Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF. J Med Genet. 2000 Jun;37(6):446-8. (http://www.ncbi.nlm.nih.gov/pubmed/10851256?dopt=Abstract)
  • Tachibana M. Cochlear melanocytes and MITF signaling. J Investig Dermatol Symp Proc. 2001 Nov;6(1):95-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11764294?dopt=Abstract)
  • Tachibana M. MITF: a stream flowing for pigment cells. Pigment Cell Res. 2000 Aug;13(4):230-40. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10952390?dopt=Abstract)
  • Widlund HR, Fisher DE. Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival. Oncogene. 2003 May 19;22(20):3035-41. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12789278?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2015
Published: February 8, 2016