E4F1

Chr 16

E4F transcription factor 1

Also known as: E4F

NCBI Gene: 1877ENSG00000167967UniProt: Q66K89

The zinc finger protein encoded by this gene is one of several cellular transcription factors whose DNA-binding activities are regulated through the action of adenovirus E1A. A 50-kDa amino-terminal product is generated from the full-length protein through proteolytic cleavage. The protein is differentially regulated by E1A-induced phosphorylation. The full-length gene product represses transcription from the E4 promoter in the absence of E1A, while the 50-kDa form acts as a transcriptional activator in its presence. Alternative splicing results in multiple transcripts encoding different proteins. [provided by RefSeq, Jan 2014]

207
ClinVar variants
35
Pathogenic / LP
0.08
pLI score
0
Active trials
Clinical Summary— E4F1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
35 Pathogenic / Likely Pathogenic· 145 VUS of 207 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.48LOEUF
pLI 0.080
Z-score 3.75
OE 0.26 (0.15–0.48)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.35Z-score
OE missense 0.83 (0.77–0.90)
424 obs / 509.5 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.0.26 (0.15–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.90)
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.1.20
0≤1.21.6
LoF obs/exp: 8 / 30.3Missense obs/exp: 424 / 509.5Syn Z: -2.39

ClinVar Variant Classifications

207 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic3
VUS145
Likely Benign9
32
Pathogenic
3
Likely Pathogenic
145
VUS
9
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
1
2
0
3
VUS
0
129
16
0
145
Likely Benign
0
7
0
2
9
Benign
0
0
0
0
0
Total0137502189

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

View in ClinVar →

Protein Context — Lollipop Plot

E4F1 · 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
Transcription factor E4F1 as a regulator of cell life and disease progression.
Sun S et al.·Sci Adv
2023Review
The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.
Lacroix M et al.·Nat Commun
2021Functional
E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells.
Chagraoui J et al.·Genes Dev
2006
Downregulation of transcription factor E4F1 in hepatocarcinoma cells: HBV-dependent effects on autophagy, proliferation and metabolism.
Dai Y et al.·Carcinogenesis
2014
Vorinostat decrease M2 macrophage polarization through ARID1A(6488delG)/HDAC6/IL-10 signaling pathway in endometriosis-associated ovarian carcinoma.
Hsieh TH et al.·Biomed Pharmacother
2023
New genes and pathomechanisms in mitochondrial disorders unraveled by NGS technologies.
Legati A et al.·Biochim Biophys Acta
2016Functional
Drug Targeting and Biomarkers in Head and Neck Cancers: Insights from Systems Biology Analyses.
Islam T et al.·OMICS
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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