MITF

Chr 3ARAD

melanocyte inducing transcription factor

Also known as: CMM8, COMMAD, MI, MITF-A, WS2, WS2A, bHLHe32

NCBI Gene: 4286 ENSG00000187098 UniProt: O75030 OMIM: 156845

MITF encodes a transcription factor that serves as a master regulator of melanocyte survival and differentiation, binding to promoter regions of pigmentation genes like tyrosinase to control melanin production. Mutations cause auditory-pigmentary syndromes including Waardenburg syndrome type 2A, Tietz albinism-deafness syndrome, and COMMAD syndrome, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.31), reflecting its critical role in melanocyte development and pigmentation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a transcription factor that contains both basic helix-loop-helix and leucine zipper structural features. The encoded protein regulates melanocyte development and is responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the this gene cause auditory-pigmentary syndromes, such as Waardenburg syndrome type 2 and Tietz syndrome. [provided by RefSeq, Aug 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Melanoma, cutaneous malignant, susceptibility to, 8}MIM #614456

COMMAD syndromeMIM #617306

Tietz albinism-deafness syndromeMIM #103500

Waardenburg syndrome, type 2AMIM #193510

UniProtColoboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness

Clinical highlights

Gene-disease validity (ClinGen)

Waardenburg syndrome type 2 · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

437

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.31

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

📖