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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MAML1
mastermind like transcriptional coactivator 1
Chromosome 5 · 5q35.3
NCBI Gene: 9794Ensembl: ENSG00000161021.14HGNC: HGNC:13632UniProt: Q92585
111PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleusprotein kinase bindingMAML1-RBP-Jkappa- ICN1 complexpeptide antigen bindingcancerenteritisperipheral vertigoinsomnia
✦AI Summary

MAML1 (mastermind like transcriptional coactivator 1) is a multifunctional transcriptional coregulator that serves as a critical coactivator for Notch signaling pathways. MAML1 forms a ternary complex with the intracellular domain of Notch (ICN) and the DNA-binding protein CSL, enhancing Notch-induced transcription of target genes such as HES-1 1. Beyond Notch signaling, MAML1 functions as a coactivator for diverse transcription factors including p53, MEF2C, and β-catenin, and interacts with histone acetyltransferase p300 to increase its activity 2. The protein exhibits global effects on cellular processes, influencing DNA methylation patterns and gene expression across thousands of CpG sites, particularly affecting genes involved in urogenital system development and embryogenesis 3. In disease contexts, MAML1 demonstrates oncogenic properties across multiple cancer types. In hepatocellular carcinoma, YAP-induced MAML1 cooperates with STAT3 to drive tumor progression through p300-dependent STAT3 acetylation 4. MAML1 also promotes triple-negative breast cancer aggressiveness by regulating Notch1 and Gli1 stability through inhibition of the E3 ubiquitin ligase Itch 5. These findings establish MAML1 as both a developmental regulator and potential therapeutic target in cancer.

Sources cited
1
MAML1 forms ternary complex with Notch ICN and CSL, enhances HES-1 transcription
PMID: 15019995
2
MAML1 functions as coactivator for p53, MEF2C, β-catenin and interacts with p300
PMID: 19751190
3
MAML1 affects DNA methylation patterns and gene expression globally, particularly in urogenital development genes
PMID: 26857655
4
YAP-induced MAML1 cooperates with STAT3 in hepatocellular carcinoma through p300-dependent acetylation
PMID: 41345959
5
MAML1 drives triple-negative breast cancer by regulating Notch1/Gli1 stability via Itch inhibition
PMID: 41272291
Disease Associationsⓘ20
cancerOpen Targets
0.58Moderate
enteritisOpen Targets
0.18Weak
peripheral vertigoOpen Targets
0.18Weak
insomniaOpen Targets
0.16Weak
Abnormality of the skeletal systemOpen Targets
0.12Weak
Familial prostate cancerOpen Targets
0.11Weak
prostate cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
Distal myopathy, Nonaka typeOpen Targets
0.05Suggestive
GNE myopathyOpen Targets
0.04Suggestive
tibial muscular dystrophyOpen Targets
0.04Suggestive
myopathy, distal, 6, adult-onset, autosomal dominantOpen Targets
0.04Suggestive
exercise intolerance, riboflavin-responsiveOpen Targets
0.04Suggestive
autosomal recessive limb-girdle muscular dystrophy type 2LOpen Targets
0.04Suggestive
myopathy, sarcoplasmic bodyOpen Targets
0.04Suggestive
Proximal spinal muscular atrophy type 4Open Targets
0.04Suggestive
spinal muscular atrophy, type IVOpen Targets
0.04Suggestive
myopathy, distal, 5Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MYCProtein interaction100%DTX1Protein interaction99%NCOR1Protein interaction96%DLL1Protein interaction94%CDK8Protein interaction94%EP300Protein interaction94%
Tissue Expression6 tissues
Ovary
100%
Lung
76%
Liver
50%
Bone Marrow
48%
Heart
47%
Brain
41%
Gene Interaction Network
Click a node to explore
MAML1MYCDTX1NCOR1DLL1CDK8EP300
PROTEIN STRUCTURE
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PDB6SMV · 2.14 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.19 [0.13–0.30]
RankingsWhere MAML1 stands among ~20K protein-coding genes
  • #4,278of 20,598
    Most Researched111 · top quartile
  • #1,132of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedMAML1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Transcriptional mechanisms by the coregulator MAML1.
PMID: 19751190
Curr Protein Pept Sci · 2009
1.00
2
The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells.
PMID: 26857655
Mol Biol Rep · 2016
0.90
3
NR1D1::MAML1 epithelioid and spindle cell sarcoma mimicking pseudomyogenic hemangioendothelioma in core biopsy: A case report and review of the literature.
PMID: 37326138
Genes Chromosomes Cancer · 2023
0.80
4
Cloning and functional characterization of the murine mastermind-like 1 (Maml1) gene.
PMID: 15019995
Gene · 2004
0.70
5
YAP-induced MAML1 cooperates with STAT3 to drive hepatocellular carcinoma progression.
PMID: 41345959
Exp Hematol Oncol · 2025
0.60