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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EPC1
enhancer of polycomb 1
Chromosome 10 · 10p11.22
NCBI Gene: 80314Ensembl: ENSG00000120616.16HGNC: HGNC:19876UniProt: Q9H2F5
77PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHomologous RecombinationTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of transcription by RNA polymerase IInegative regulation of gene expression, epigeneticpositive regulation of transcription by RNA polymerase IIprotein bindingneurodegenerative diseaseosteoarthritis, hipandrogenetic alopeciaAbnormality of the skeletal system
✦AI Summary

EPC1 (enhancer of polycomb 1) is a non-catalytic component of the NuA4/TIP60 histone acetyltransferase complex that functions as a master regulator of transcription and DNA repair. Within the complex, EPC1 recruits MBTD1 through a distinct hydrophobic interaction domain 1, facilitating histone H4 and H2A acetylation at target genes 2. EPC1 plays a direct role in homologous recombination-mediated DNA double-strand break repair by promoting NuA4-dependent histone modifications that block 53BP1 binding 1. Beyond its canonical chr10 remodeling functions, EPC1 exhibits oncogenic activity in multiple cancer types. In cancer cells, EPC1 physically interacts with transcription factor E2F1 to suppress pro-apoptotic genes (like TP53 targets) while activating anti-apoptotic survival genes (BCL-2, Survivin) and metastasis-related signatures 3. EPC1 is significantly upregulated in nasopharyngeal carcinoma tissues and cell lines, where EPC1 knockdown inhibits proliferation, invasion, and epithelial-mesenchymal transition 4. Similarly, EPC1 sustains leukemia stem cell potential in MLL-mutated acute myeloid leukemia by preventing MYC protein accumulation 5. EPC1 mutations are recurrently identified in pancreatic ductal adenocarcinoma 6, supporting its established pro-cancer role across multiple malignancies.

Sources cited
1
EPC1 is a component of the human TIP60 complex with structural architecture showing EPC1 network interactions with DMAP1 and EP400 in the ARP module
PMID: 39154037
2
EPC1 recruits MBTD1 into the NuA4/TIP60 complex through a hydrophobic C-terminal interaction domain, regulating DNA repair pathway choice
PMID: 32209463
3
EPC1 physically interacts with E2F1 to activate anti-apoptotic genes and suppress pro-apoptotic targets, promoting tumor cell survival and metastasis
PMID: 26350215
4
EPC1 is significantly upregulated in nasopharyngeal carcinoma; EPC1 knockdown inhibits cell growth, induces apoptosis, and inhibits epithelial-mesenchymal transition
PMID: 34841830
5
EPC1 is critical for MLL-mutated AML leukemia stem cell potential by preventing MYC protein accumulation; selective to cancer cells versus normal hematopoietic stem cells
PMID: 24166297
6
EPC1 mutations identified as significantly mutated genes in pancreatic ductal adenocarcinoma exome sequencing cohort
PMID: 23103869
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
osteoarthritis, hipOpen Targets
0.44Moderate
androgenetic alopeciaOpen Targets
0.44Moderate
Abnormality of the skeletal systemOpen Targets
0.43Moderate
Varicose veinsOpen Targets
0.31Weak
total hip arthroplastyOpen Targets
0.31Weak
portal hypertensionOpen Targets
0.27Weak
atrial fibrillationOpen Targets
0.14Weak
cancerOpen Targets
0.08Suggestive
head and neck squamous cell carcinomaOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.06Suggestive
Tietze syndromeOpen Targets
0.05Suggestive
ghosal hematodiaphyseal dysplasiaOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
autosomal recessive hypophosphatemic ricketsOpen Targets
0.03Suggestive
12q14 microdeletion syndromeOpen Targets
0.03Suggestive
melorheostosisOpen Targets
0.03Suggestive
osteomesopyknosisOpen Targets
0.03Suggestive
pyknoachondrogenesisOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
H2AC20Protein interaction100%H2AC18Protein interaction100%TRRAPProtein interaction100%KANSL2Protein interaction100%KANSL3Protein interaction100%H2AZ1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
37%
Heart
27%
Lung
26%
Brain
22%
Liver
21%
Gene Interaction Network
Click a node to explore
EPC1H2AC20H2AC18TRRAPKANSL2KANSL3H2AZ1
PROTEIN STRUCTURE
Preparing viewer…
PDB6NFX · 1.95 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.23Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.09–0.23]
RankingsWhere EPC1 stands among ~20K protein-coding genes
  • #6,153of 20,598
    Most Researched77
  • #632of 17,882
    Most Constrained (LOEUF)0.23 · top 5%
Genes detectedEPC1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Structure of the human TIP60 complex.
PMID: 39154037
Nat Commun · 2024
1.00
2
Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.
PMID: 23103869
Nature · 2012
0.90
3
Modeling Epithelial Homeostasis and Perturbation in Three-Dimensional Human Esophageal Organoids.
PMID: 39334892
Biomolecules · 2024
0.80
4
Epigenetic factor EPC1 is a master regulator of DNA damage response by interacting with E2F1 to silence death and activate metastasis-related gene signatures.
PMID: 26350215
Nucleic Acids Res · 2016
0.70
5
Expression and Biological Functions of EPC1 in Nasopharyngeal Carcinoma.
PMID: 34841830
Arch Iran Med · 2021
0.60