Skip navigation

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

URL of this page: https://medlineplus.gov/genetics/gene/mitf/

MITF gene

melanocyte inducing transcription factor

Normal Function

The MITF gene provides instructions for making a protein that acts a transcription factor. To carry out this role, the MITF protein attaches to specific areas of DNA and helps control the activity of particular genes.

The MITF protein plays a major role in controlling the development and function of pigment-producing cells called melanocytes. Within these cells, the MITF protein controls the 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 specialized light-sensitive tissue that lines the back of the eye. Some research indicates that the MITF protein also regulates the development of the cells that break down and remove bone (osteoclasts) and the cells that play a role in allergic reactions (mast cells).

The structure of the MITF protein includes three critically important regions. Two of the regions, called the helix-loop-helix motif and the leucine-zipper motif, allow MITF proteins to interact with each other or with other proteins, 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.

Health Conditions Related to Genetic Changes

Melanoma

Genetic changes that contribute to disease are called pathogenic variants. Pathogenic variants in the MITF gene have been found in people with an aggressive form of skin cancer called melanoma. Most of these variants are somatic, meaning that they occur during a person's lifetime and are present only in the cells that give rise to melanoma. Occasionally, MITF gene variants that are associated with melanoma are inherited and are found in every cell of the body. These are known as germline variants. 

Some of the MITF gene variants that are associated with melanoma increase the rate of cell growth and division (proliferation) directly. Other variants have an indirect effect, increasing the activity of other genes that are involved in proliferation. This causes the abnormal cell growth that occurs in people with melanoma. 

More About This Health Condition

Tietz syndrome

Pathogenic variants in the MITF gene can cause a condition called Tietz syndrome, which is characterized by hearing loss that is present from birth and unusually light-colored skin and hair (hypopigmentation). Researchers suggest that Tietz syndrome may be a severe form of Waardenburg syndrome (described below). 

The pathogenic variants in the MITF gene that are associated with Tietz syndrome cause either a deletion or a substitution of a single protein building block (amino acid) in the basic motif region of the MITF protein. Dimers with the abnormal protein cannot bind to DNA. Because the altered MITF protein prevents the dimer from functioning, the protein is said to have a dominant-negative effect. Since the dimer cannot bind to DNA, the activity of the genes that are involved in the development of melanocytes and the production of melanin is impaired. A lack of melanocytes in the inner ear leads to hearing loss. Decreased melanin production also accounts for the light skin and hair color that are characteristic of Tietz syndrome. 

More About This Health Condition

Waardenburg syndrome

Pathogenic variants in the MITF gene have been identified in people with Waardenburg syndrome type II, a disorder that can cause hearing loss and changes in the pigmentation of the hair, skin, and eyes. Some MITF gene variants change the amino acids used to make the MITF protein, which alters the helix-loop-helix or leucine-zipper motif. Other variants result in an abnormally short version of the protein. Researchers believe that both types of variants disrupt the formation of dimers. Without a sufficient number of dimers, cells in certain areas of the skin, hair, eyes, and inner ear may not produce enough melanocytes. This shortage leads to hearing loss and the patchy loss of pigmentation associated with Waardenburg syndrome type II.

More About This Health Condition

Anophthalmia/Microphthalmia

MedlinePlus Genetics provides information about Anophthalmia/Microphthalmia

More About This Health Condition

Other disorders

Pathogenic variants in the MITF gene can cause a rare condition called COMMAD syndrome. The name of the condition is an acronym of the major features: coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness. A coloboma is a missing piece of tissue in one of the structures that form the eyes. Osteopetrosis is a bone disease that makes bone tissue abnormally compact, dense, and prone to breakage (fracture). Microphthalmia are unusually small eyes and macrocephaly is an unusually large head. Albinism is abnormally light coloring of the skin, hair, and eyes. In people with COMMAD syndrome, deafness is caused by abnormalities of the inner ear (sensorineural hearing loss) and is present from birth. 

Unlike Tietz syndrome and Waardenburg syndrome, which are caused by a pathogenic variant in one copy of the MITF gene in each cell, COMMAD syndrome is caused by variants in both copies of the MITF gene in each cell. It is likely that these variants critically reduce the activity of the MITF protein, impairing its ability to regulate gene activity and causing the severe signs and symptoms of COMMAD syndrome. 

Other Names for This Gene

  • melanogenesis associated transcription factor
  • microphthalmia-associated transcription factor
  • WS2
  • WS2A

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Centeno PP, Pavet V, Marais R. The journey from melanocytes to melanoma. Nat Rev Cancer. 2023 Jun;23(6):372-390. doi: 10.1038/s41568-023-00565-7. Epub 2023 Apr 24. Citation on PubMed
  • George A, Zand DJ, Hufnagel RB, Sharma R, Sergeev YV, Legare JM, Rice GM, Scott Schwoerer JA, Rius M, Tetri L, Gamm DM, Bharti K, Brooks BP. Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness. Am J Hum Genet. 2016 Dec 1;99(6):1388-1394. doi: 10.1016/j.ajhg.2016.11.004. Epub 2016 Nov 23. Citation on PubMed
  • Grill C, Bergsteinsdottir K, Ogmundsdottir MH, Pogenberg V, Schepsky A, Wilmanns M, Pingault V, Steingrimsson 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. Citation on PubMed or Free article on PubMed Central
  • Gudmundsdottir DH, de Lomana ALG, Venkatesh TB, Kirty K, Sigurdsson S, Vidarsdottir L, Dilshat R, Sveinbjornsdottir E, Ragnarsdottir S, Magnusson DH, Bustos MR, Steingrimsson E, Gudjonsson T, Sigurdsson S. MITF maintains genome stability in nonmelanocyte lineages. Mol Oncol. 2026 Jun 10. doi: 10.1002/1878-0261.70273. Online ahead of print. Citation on PubMed
  • Hida T, Kamiya T, Kawakami A, Ogino J, Sohma H, Uhara H, Jimbow K. Elucidation of Melanogenesis Cascade for Identifying Pathophysiology and Therapeutic Approach of Pigmentary Disorders and Melanoma. Int J Mol Sci. 2020 Aug 25;21(17):6129. doi: 10.3390/ijms21176129. Citation on PubMed
  • 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. No abstract available. Citation on PubMed
  • Leger 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. Citation on PubMed or Free article on PubMed Central
  • 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. doi: 10.1007/s004390000328. Citation on PubMed
  • Tachibana M. Cochlear melanocytes and MITF signaling. J Investig Dermatol Symp Proc. 2001 Nov;6(1):95-8. doi: 10.1046/j.0022-202x.2001.00017.x. Citation on PubMed
  • Tachibana M. MITF: a stream flowing for pigment cells. Pigment Cell Res. 2000 Aug;13(4):230-40. doi: 10.1034/j.1600-0749.2000.130404.x. Citation on PubMed
  • 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. doi: 10.1038/sj.onc.1206443. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.