E2F3

Chr 6

E2F transcription factor 3

Also known as: E2F-3

NCBI Gene: 1871ENSG00000112242UniProt: O00716

This gene encodes a member of a small family of transcription factors that function through binding of DP interaction partner proteins. The encoded protein recognizes a specific sequence motif in DNA and interacts directly with the retinoblastoma protein (pRB) to regulate the expression of genes involved in the cell cycle. Altered copy number and activity of this gene have been observed in a number of human cancers. There are pseudogenes for this gene on chromosomes 2 and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

60
ClinVar variants
13
Pathogenic / LP
0.95
pLI score· haploinsufficient
0
Active trials
Clinical Summary— E2F3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 43 VUS of 60 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.35LOEUF
pLI 0.946
Z-score 3.50
OE 0.11 (0.04–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.59Z-score
OE missense 0.72 (0.64–0.81)
180 obs / 250.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.04–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.64–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 2 / 18.0Missense obs/exp: 180 / 250.9Syn Z: 0.84

ClinVar Variant Classifications

60 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS43
Likely Benign2
Benign2
13
Pathogenic
43
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
0
0
0
VUS
0
39
4
0
43
Likely Benign
0
1
0
1
2
Benign
0
2
0
0
2
Total04217160

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

E2F3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF-β and TNFSF13B/VEGF-A Axis.
Yin L et al.·Adv Sci (Weinh)
2023
PA28γ coordinates the cross-talk between cancer-associated fibroblasts and tumor cells to promote OSCC progression via HDAC1/E2F3/IGF2 signaling.
Li Z et al.·Cancer Lett
2024
Targeting p16(INK4a)-mediated cellular senescence as a therapeutic strategy for FLT3-ITD-driven acute myeloid leukemia.
Zheng J et al.·Leukemia
2025
miR-449a: A Promising Biomarker and Therapeutic Target in Cancer and Other Diseases.
Barati T et al.·Cell Biochem Biophys
2024Review
Curtailing overexpression of E2F3 in breast cancer using siRNA (E2F3)-based gene silencing.
Vimala K et al.·Arch Med Res
2012
Critical Roles of E2F3 in Growth and Musculo-skeletal Phenotype in Mice.
Kim HR et al.·Int J Med Sci
2019
Tumor-associated macrophages promote cholangiocarcinoma progression via exosomal Circ_0020256.
Chen S et al.·Cell Death Dis
2022
Identification of a novel circRNA-miRNA-mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis.
Zhong G et al.·Sci Rep
2023
Identification of a novel prognostic signature composed of 3 cuproptosis-related transcription factors in colon adenocarcinoma.
Zhou L et al.·Genes Genomics
2023
E2F1/CKS2/PTEN signaling axis regulates malignant phenotypes in pediatric retinoblastoma.
Chen M et al.·Cell Death Dis
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Long Noncoding RNA SATB1-AS1 Suppresses Inflammatory Response and Injury in Dental Pulp Stem Cells Through the miR-15a-5p/E2F3 Axis.
Ding S et al.·Int Dent J
2026🔓 Open Access
Time-Dependent Loss of miR-548c-3p and Activation of E2F3/FOXM1 in Breast Cancer: In Vitro and TCGA-Based Evidence for a Post-Transcriptional Mechanism.
Bozkurt B et al.·Int J Mol Sci
2026🔓 Open AccessFunctional
Circ_0001741 regulates proliferation and invasion in ESCC via the miR-194-5p/E2F3 axis.
Wang Y et al.·World J Surg Oncol
2025🔓 Open Access
IgD in nucleus of pro-B cells promotes pro-B cells proliferation by regulating E2F3 expression.
Zhang Y et al.·Cell Biosci
2025🔓 Open Access
Euxanthone Inhibits Hepatocellular Carcinoma Progression by Targeting the miR-199a-5p/E2F3 Regulatory Axis.
Al Awadh AA.·Anticancer Agents Med Chem
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools