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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MAFF
MAF bZIP transcription factor F
Chromosome 22 · 22q13.1
NCBI Gene: 23764Ensembl: ENSG00000185022.14HGNC: HGNC:6780UniProt: Q9ULX9
58PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of transcription by RNA polymerase IInucleoplasmDNA-binding transcription activator activity, RNA polymerase II-specificprotein bindingAbnormality of the skeletal systemdiverticular diseasediabetes mellitusmelanoma
✦AI Summary

MAFF (MAF bZIP transcription factor F) is a basic region leucine zipper transcription factor that functions as both a transcriptional repressor and activator depending on its dimerization partners 1. As a homodimer, MAFF lacks a transactivation domain and acts as a transcriptional repressor 1. However, when forming heterodimers with larger basic-zipper proteins such as NFE2L2/NRF2 or BACH1, MAFF functions as a transcriptional activator, recruiting partners to specific DNA-binding sites 1. In cancer contexts, MAFF exhibits tumor-suppressive properties. In lung adenocarcinoma, MAFF inhibits tumor cell proliferation by regulating SLC7A11, CDK6, and CDKN2C expression, promoting ferroptosis and preventing G1-to-S cell cycle progression 2. Reduced MAFF expression correlates with worse clinical outcomes and cisplatin resistance in lung adenocarcinoma 2. Similarly, in colorectal cancer, MAFF protein is downregulated and reduced expression predicts poor overall and disease-free survival; BAP1-mediated deubiquitination stabilizes MAFF, which suppresses CRC growth through DUSP5/ERK inhibition 3. Conversely, MAFF exhibits context-dependent functions in other disease contexts. In breast cancer, hypoxia-induced MAFF promotes tumor invasion and metastasis through IL11/STAT3 signaling 4. In atherosclerosis, MAFF regulates LDLR expression in a context-dependent manner: positively under non-inflammatory conditions and negatively when complexed with BACH1 during inflammatory stimulation 5. MAFF also participates in Nrf2-dependent oxidative stress responses relevant to acute lung injury 6.

Sources cited
1
MAFF is a bZIP transcription factor that acts as a repressor in homodimers and as an activator in heterodimers with CNC/Bach proteins
PMID: 27058431
2
MAFF suppresses lung adenocarcinoma growth by regulating ferroptosis and cell cycle genes; reduced MAFF expression correlates with worse outcomes and treatment resistance
PMID: 38266355
3
MAFF protein is downregulated in colorectal cancer; BAP1 deubiquitinates MAFF to stabilize it, suppressing CRC growth through DUSP5/ERK inhibition
PMID: 39151323
4
Hypoxia-induced MAFF promotes breast cancer invasion and metastasis through IL11/STAT3 signaling via MAFF-BACH1 heterodimers
PMID: 34262028
5
MAFF regulates LDLR expression with context-dependent effects: positive correlation under non-inflammatory conditions and negative correlation with BACH1 heterodimers during inflammation
PMID: 33626882
6
MAFF participates in Nrf2-dependent antioxidant responses relevant to acute lung injury via the Nrf2-MAFF/ARE pathway
PMID: 33752110
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.46Moderate
diverticular diseaseOpen Targets
0.43Moderate
diabetes mellitusOpen Targets
0.43Moderate
melanomaOpen Targets
0.42Moderate
pelvic organ prolapseOpen Targets
0.41Moderate
benign neoplasm of skinOpen Targets
0.40Moderate
skin cancerOpen Targets
0.40Moderate
alcohol drinkingOpen Targets
0.40Weak
cutaneous melanomaOpen Targets
0.40Weak
basal cell carcinomaOpen Targets
0.39Weak
breast cancerOpen Targets
0.37Weak
skin neoplasmOpen Targets
0.36Weak
type 2 diabetes mellitusOpen Targets
0.35Weak
melanocytic nevusOpen Targets
0.32Weak
metabolic syndromeOpen Targets
0.31Weak
prolapse of female genital organOpen Targets
0.31Weak
uterine prolapseOpen Targets
0.31Weak
Abnormality of refractionOpen Targets
0.21Weak
neurodegenerative diseaseOpen Targets
0.20Weak
seborrheic keratosisOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BACH2Protein interaction96%BACH1Protein interaction90%NFE2Protein interaction90%NFE2L1Protein interaction90%NFE2L2Protein interaction90%ATF3Protein interaction85%
Tissue Expression6 tissues
Lung
100%
Ovary
57%
Bone Marrow
41%
Liver
23%
Brain
18%
Heart
11%
Gene Interaction Network
Click a node to explore
MAFFBACH2BACH1NFE2NFE2L1NFE2L2ATF3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9ULX9
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.95LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.76 [0.92–1.95]
RankingsWhere MAFF stands among ~20K protein-coding genes
  • #7,889of 20,598
    Most Researched58
  • #17,690of 17,882
    Most Constrained (LOEUF)1.95
Genes detectedMAFF
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma.
PMID: 38266355
Drug Resist Updat · 2024
1.00
2
Transcription factor NFE2L2/NRF2 modulates chaperone-mediated autophagy through the regulation of LAMP2A.
PMID: 29950142
Autophagy · 2018
0.90
3
MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism.
PMID: 33752110
Redox Biol · 2021
0.80
4
The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling.
PMID: 34262028
Nat Commun · 2021
0.70
5
Characterization of human transcription factor function and patterns of gene regulation in HepG2 cells.
PMID: 37852782
Genome Res · 2023
0.60