MITF

Highest pathogenic variant AF is 0.0027823313

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000352241

Coding exons

10

Length

228903

Individuals with no LoFs

125704

Homozygous LoFs

0

Heterozygous LoFs

4

Defined

125708

p

0.0000159

Function

FUNCTION: Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium. {ECO:0000269|PubMed:10587587, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:27889061, ECO:0000269|PubMed:9647758}.;

Disease

DISEASE: Waardenburg syndrome 2A (WS2A) [MIM:193510]: WS2 is a genetically heterogeneous, autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, and absence of dystopia canthorum. The frequency of deafness is higher in WS2 than in WS1. {ECO:0000269|PubMed:28236341, ECO:0000269|PubMed:8589691}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Waardenburg syndrome 2, with ocular albinism, autosomal recessive (WS2-OA) [MIM:103470]: A disorder characterized by the association of features typical of Waardenburg syndrome type 2 with ocular albinism. Patients manifest reduced visual acuity, albinotic fundus, deafness, hypomelanosis. {ECO:0000269|PubMed:9647758}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Tietz albinism-deafness syndrome (TADS) [MIM:103500]: An autosomal dominant disorder characterized by generalized hypopigmentation and congenital, bilateral, profound sensorineural deafness. {ECO:0000269|PubMed:10851256}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Melanoma, cutaneous malignant 8 (CMM8) [MIM:614456]: A malignant neoplasm of melanocytes, arising de novo or from a pre- existing benign nevus, which occurs most often in the skin but also may involve other sites. {ECO:0000269|PubMed:22012259, ECO:0000269|PubMed:22080950}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD) [MIM:617306]: An autosomal recessive syndrome characterized by severe microphthalmia, profound congenital sensorineural hearing loss, lack of pigment in the hair, skin, and eyes, macrocephaly, facial dysmorphism, and osteopetrosis. {ECO:0000269|PubMed:27889061}. Note=The disease is caused by mutations affecting the gene represented in this entry. An allelic combination involving at least one dominant-negative mutation, inherited in a recessive manner, represents the underlying molecular mechanism leading to COMMAD syndrome. {ECO:0000269|PubMed:27889061}.; DISEASE: Note=Variations affecting this gene are associated with susceptibility to pheochromocytomas and paragangliomas, rare neural crest-derived tumors with an approximate incidence of 1:300,000/year. {ECO:0000269|PubMed:27680874}.;