MITF Gene - Microphthalmia-Associated Transcription Factor
Key regulator of melanocyte development, pigmentation, and melanoma pathogenesis
Gene Information Card
| Symbol | MITF |
|---|---|
| Full Name | Microphthalmia-Associated Transcription Factor |
| Gene Type | Protein coding |
| Chromosomal Location | 3p13 |
| NCBI Gene ID | 4286 ncbi.nlm.nih.gov/gene/4286 |
| Ensembl ID | ENSG00000187098 |
| UniProt ID | O75030 |
| OMIM ID | 156845 |
| HGNC ID | 7105 |
| Aliases | bHLHe32, MI, WS2A, CMM8, COMMAD |
Description
MITF encodes a basic helix-loop-helix leucine zipper transcription factor that regulates melanocyte development, differentiation, and survival. It controls expression of melanogenic enzymes (TYR, TYRP1, DCT) and is a master regulator of pigmentation. MITF also plays roles in osteoclast development, mast cell function, and is implicated in melanoma oncogenesis. Mutations cause Waardenburg syndrome type 2A, Tietz syndrome, and predispose to melanoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma (cutaneous malignant melanoma 8) | MITF amplification or activating mutations promote melanocyte proliferation and survival; loss of function can also contribute to tumor progression | COSMIC, ClinVar, OMIM #614456 |
| Waardenburg syndrome type 2A | Heterozygous loss-of-function mutations in MITF disrupt melanocyte migration and differentiation, leading to hearing loss and pigmentation defects | OMIM #193510, ClinVar |
| Tietz syndrome | Homozygous or compound heterozygous MITF mutations cause severe hearing loss and albinoid hypopigmentation | OMIM #103500, ClinVar |
| COMMAD syndrome | Biallelic MITF mutations result in coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness | OMIM #617306, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Retina | 8.2 | Medium |
| Heart | 1.3 | Low |
| Brain | 0.5 | Not detected |
| Lung | 0.8 | Low |
| Kidney | 0.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SK-MEL-28 (melanoma) | 45.6 | High expression |
| A375 (melanoma) | 38.2 | High expression |
| HEK293 (embryonic kidney) | 0.3 | Not detected |
| MCF7 (breast cancer) | 1.1 | Low |
| HepG2 (liver cancer) | 0.4 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.952G>A (p.Glu318Lys) | Missense | <0.1% | Dominant negative; associated with Waardenburg syndrome type 2A |
| c.647G>A (p.Arg216Gln) | Missense | <0.1% | Loss of function; Tietz syndrome |
| c.328C>T (p.Arg110*) | Nonsense | <0.1% | Loss of function; Waardenburg syndrome |
| Amplification (3p13) | Copy number gain | 5-10% in melanoma | Gain of function; promotes melanoma progression |
| c.649C>T (p.Arg217Trp) | Missense | <0.1% | Dominant negative; COMMAD syndrome |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and some missense mutations (e.g., p.Arg216Gln) reduce or abolish DNA binding and transactivation, leading to hypopigmentation and hearing loss.
Gain of Function (GOF)
Gene amplification or activating missense mutations (e.g., p.Glu318Lys in rare contexts) enhance MITF activity, driving melanocyte proliferation and melanoma.
Dominant Negative (DN)
Missense mutations in the basic domain (e.g., p.Arg217Trp, p.Glu318Lys) produce proteins that dimerize with wild-type MITF but fail to bind DNA, inhibiting normal function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Melanogenesis (KEGG hsa04916)
• Signaling pathways regulating pluripotency of stem cells (KEGG hsa04550)
• cAMP signaling pathway (KEGG hsa04024)
• MAPK signaling pathway (KEGG hsa04010)
• Wnt signaling pathway (KEGG hsa04310)
Protein Summary
MITF is a 419-amino acid basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factor. It forms homodimers or heterodimers with TFE3, TFEB, or TFEC. MITF binds to E-box elements (CANNTG) in target gene promoters. It is phosphorylated by MAPK, GSK3β, and other kinases, regulating its stability and activity. MITF is essential for melanocyte survival, differentiation, and pigmentation. In melanoma, MITF acts as a lineage-specific oncogene, with amplification or overexpression driving tumor progression. Isoforms include MITF-M (melanocyte-specific), MITF-A, MITF-H, and MITF-C.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MITF Knockout HEK293 Cell Line | EDJ-KQ3525 | Human | 4286 | Details Get a Quote |
| MITF Knockout A-549 Cell Line | EDJ-KQ25358 | Human | 4286 | Details Get a Quote |
| MITF Knockout HCT 116 Cell Line | EDJ-KQ25359 | Human | 4286 | Details Get a Quote |
| MITF Knockout HeLa Cell Line | EDJ-KQ25360 | Human | 4286 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
