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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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E4F1
E4F transcription factor 1
Chromosome 16 Β· 16p13.3
NCBI Gene: 1877Ensembl: ENSG00000167967.16HGNC: HGNC:3121UniProt: H3BSL4
46PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
RNA polymerase II transcription regulatory region sequence-specific DNA bindingDNA-binding transcription repressor activity, RNA polymerase II-specificDNA-binding transcription activator activity, RNA polymerase II-specificprotein bindingneurodegenerative diseasepyruvate dehydrogenase deficiencyneoplasmAbnormality of the skeletal system
✦AI Summary

E4F1 (E4F transcription factor 1) is a zinc finger transcription factor that serves as a master regulator of multiple cellular processes critical for cell survival and genome integrity 1. The protein functions through direct DNA binding to regulate transcription of key target genes, including DLAT and ELP3, which encode subunits of the pyruvate dehydrogenase complex and Elongator complex respectively 2. E4F1 plays essential roles in cell cycle progression and DNA damage response by interacting with and stabilizing checkpoint kinase 1 (CHK1), protecting it from degradation to ensure high-fidelity DNA replication 3. The transcription factor also coordinates metabolic processes, particularly pyruvate metabolism and acetyl-CoA production, which are crucial for translation fidelity during brain development 2. In adipocytes, E4F1 interacts directly with p53 to regulate lipid metabolism, specifically controlling monounsaturated fatty acid synthesis through Stearoyl-CoA Desaturase-1 regulation 4. E4F1 demonstrates tissue-specific functions, being essential for hematopoietic cell survival while its depletion selectively kills myeloid leukemic cells through oxidative stress-mediated mechanisms 5. The protein is overexpressed in human acute myeloid leukemia, suggesting potential therapeutic targeting opportunities 5. Additionally, E4F1 functions as a specific transcriptional activator of the TERT promoter -57A>C mutation in certain cancers 6.

Sources cited
1
E4F1 is a zinc finger transcription factor regulating cell growth, proliferation, differentiation, apoptosis, DNA damage response, and metabolism
PMID: 37774036
2
E4F1 directly regulates DLAT and ELP3 genes and coordinates pyruvate metabolism with translation fidelity during brain development
PMID: 39747033
3
E4F1 interacts with and protects CHK1 from degradation, serving as a master regulator of CHK1-mediated functions in genome stability
PMID: 25843717
4
E4F1 directly interacts with p53 and co-regulates Stearoyl-CoA Desaturase-1 to control lipid metabolism in adipocytes
PMID: 34857760
5
E4F1 depletion causes oxidative stress-mediated death in myeloid leukemic cells and E4F1 is overexpressed in human acute myeloid leukemia
PMID: 21708927
6
E4F1 specifically binds to and activates the TERT promoter -57A>C mutation
PMID: 37918959
Disease Associationsβ“˜20
neurodegenerative diseaseOpen Targets
0.41Moderate
pyruvate dehydrogenase deficiencyOpen Targets
0.27Weak
neoplasmOpen Targets
0.07Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
melanomaOpen Targets
0.05Suggestive
obesityOpen Targets
0.04Suggestive
infectionOpen Targets
0.04Suggestive
cancerOpen Targets
0.03Suggestive
head and neck squamous cell carcinomaOpen Targets
0.03Suggestive
acute myeloid leukemiaOpen Targets
0.02Suggestive
triple-negative breast cancerOpen Targets
0.02Suggestive
Insulin resistanceOpen Targets
0.02Suggestive
microcephalyOpen Targets
0.01Suggestive
Leigh syndromeOpen Targets
0.01Suggestive
nasopharyngeal carcinomaOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
Glucose intoleranceOpen Targets
0.01Suggestive
rhabdomyosarcomaOpen Targets
0.01Suggestive
myeloid neoplasmOpen Targets
0.00Suggestive
Pathogenic Variants1
NM_004424.5(E4F1):c.430A>C (p.Lys144Gln)Likely pathogenic
Pyruvate dehydrogenase complex deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 144
View on ClinVar β†—
Related Genes
CDKN2AProtein interaction100%BMI1Protein interaction96%RASSF1Protein interaction89%FAAP100Protein interaction79%COMMD3-BMI1Protein interaction79%WDR24Protein interaction79%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
95%
Ovary
87%
Lung
84%
Brain
32%
Heart
32%
Gene Interaction Network
Click a node to explore
E4F1CDKN2ABMI1RASSF1FAAP100COMMD3-BMI1WDR24
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q66K89
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.64LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.47 [0.34–0.64]
RankingsWhere E4F1 stands among ~20K protein-coding genes
  • #9,322of 20,598
    Most Researched46
  • #5,125of 5,498
    Most Pathogenic Variants1
  • #4,551of 17,882
    Most Constrained (LOEUF)0.64
Genes detectedE4F1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Transcription factor E4F1 as a regulator of cell life and disease progression.
PMID: 37774036
Sci Adv Β· 2023
1.00
2
m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency.
PMID: 35340126
Clin Transl Med Β· 2022
0.90
3
E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development.
PMID: 39747033
Nat Commun Β· 2025
0.80
4
E4F1 and ZNF148 are transcriptional activators of the -57A > C and wild-type
PMID: 37918959
Genome Res Β· 2023
0.70
5
E4F1 is a master regulator of CHK1-mediated functions.
PMID: 25843717
Cell Rep Β· 2015
0.60