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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MAFA
MAF bZIP transcription factor A
Chromosome 8 · 8q24.3
NCBI Gene: 389692Ensembl: ENSG00000182759.4HGNC: HGNC:23145UniProt: Q8NHW3
52PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of transcription by RNA polymerase IIsequence-specific double-stranded DNA bindinginsulin secretionresponse to glucoseislet cell adenomatosisconnective tissue diseasejuvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndromeosteopetrosis, autosomal dominant 3
✦AI Summary

MAFA (MAF bZIP transcription factor A) is a critical transcription factor that regulates pancreatic β-cell function and insulin production. MAFA activates insulin gene expression by binding to the insulin enhancer C1/RIPE3b element and consensus TRE-type MARE DNA sequences 1. The protein acts synergistically with other key transcription factors including NEUROD1/BETA2 and PDX1 to control insulin synthesis at the transcriptional level 1. Beyond insulin gene regulation, MAFA controls the expression of exocytosis-related genes essential for insulin secretion, including STX1A, SYT7, and STXBP1, with MAFA silencing resulting in impaired insulin secretion 2. MAFA serves as a marker of mature β-cell phenotype, with its expression found in functional insulin-producing cells derived from human pluripotent stem cells that can reverse diabetes in experimental models 34. Clinically, MAFA is highly relevant to diabetes pathogenesis, as its expression is reduced in type 2 diabetes β-cells and correlates with β-cell dedifferentiation 5. Germline mutations in MAFA cause familial insulinomatosis, a rare condition characterized by multiple insulin-producing pancreatic tumors and paradoxical occurrence of diabetes mellitus within affected families 6. Additionally, MAFA translocations are associated with multiple myeloma pathogenesis 7.

Sources cited
1
MAFA regulates insulin transcription and acts synergistically with PDX1 and NeuroD1
PMID: 22974359
2
MAFA regulates exocytosis-related genes STX1A, SYT7, and STXBP1 essential for insulin secretion
PMID: 34978761
3
MAFA expression marks mature β-cell phenotype in stem cell-derived insulin-producing cells
PMID: 25211370
4
MAFA-positive cells from implanted stem cell-derived pancreatic endoderm secrete insulin in patients
PMID: 34861146
5
MAFA expression is associated with β-cell dedifferentiation in type 2 diabetes
PMID: 40072535
6
MAFA mutations cause familial insulinomatosis with paradoxical diabetes occurrence
PMID: 36952647
7
MAFA translocations are associated with multiple myeloma pathogenesis
PMID: 38199896
Disease Associationsⓘ21
islet cell adenomatosisOpen Targets
0.57Moderate
connective tissue diseaseOpen Targets
0.18Weak
juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndromeOpen Targets
0.12Weak
osteopetrosis, autosomal dominant 3Open Targets
0.12Weak
type 1 diabetes mellitusOpen Targets
0.10Weak
MODYOpen Targets
0.10Weak
type 2 diabetes mellitusOpen Targets
0.09Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.07Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.07Suggestive
maturity-onset diabetes of the young type 4Open Targets
0.07Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.07Suggestive
hyperinsulinism due to glucokinase deficiencyOpen Targets
0.07Suggestive
diabetes mellitusOpen Targets
0.06Suggestive
maturity-onset diabetes of the young type 2Open Targets
0.06Suggestive
maturity-onset diabetes of the young type 6Open Targets
0.06Suggestive
diabetes mellitus, transient neonatal, 2Open Targets
0.06Suggestive
exercise-induced hyperinsulinismOpen Targets
0.06Suggestive
hyperproinsulinemiaOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
Combined pituitary hormone deficiencies, genetic formsOpen Targets
0.06Suggestive
Insulinomatosis and diabetes mellitusUniProt
Pathogenic Variants2
NM_201589.4(MAFA):c.170C>G (p.Thr57Arg)Pathogenic
Islet cell adenomatosis
★☆☆☆2023→ Residue 57
NM_201589.4(MAFA):c.191C>T (p.Ser64Phe)Likely pathogenic
Islet cell adenomatosis
★☆☆☆2018→ Residue 64
View on ClinVar ↗
Related Genes
PDX1Protein interaction79%NEUROD1Protein interaction79%SLC2A2Protein interaction79%NEUROG3Protein interaction79%INSProtein interaction78%FAM3BShared pathway50%
Tissue Expression6 tissues
Heart
100%
Brain
78%
Lung
67%
Bone Marrow
44%
Ovary
0%
Liver
0%
Gene Interaction Network
Click a node to explore
MAFAPDX1NEUROD1SLC2A2NEUROG3INSFAM3B
PROTEIN STRUCTURE
Preparing viewer…
PDB4EOT · 2.86 Å · X-ray
View on RCSB ↗
RankingsWhere MAFA stands among ~20K protein-coding genes
  • #8,579of 20,598
    Most Researched52
  • #4,428of 5,498
    Most Pathogenic Variants2
Genes detectedMAFA
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis.
PMID: 38050068
Gut · 2024
1.00
2
Molecular Pathogenesis of Multiple Myeloma: Clinical Implications.
PMID: 38199896
Hematol Oncol Clin North Am · 2024
0.90
3
Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes.
PMID: 34861146
Cell Stem Cell · 2021
0.80
4
Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells.
PMID: 25211370
Nat Biotechnol · 2014
0.70
5
Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes.
PMID: 22974359
Curr Diabetes Rev · 2013
0.60