E4F1

Chr 16

E4F transcription factor 1

Also known as: E4F

NCBI Gene: 1877 ENSG00000167967 UniProt: Q66K89 OMIM: 603022

E4F1 encodes a zinc finger transcription factor that regulates cell cycle progression and functions in the p53 and pRB tumor suppressor pathways, including control of cyclin A2 transcription. The gene is highly constrained against loss-of-function variants (LOEUF 0.48), but specific disease associations have not been established based on the provided information. An inheritance pattern cannot be determined from the available data.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.48

Clinical Summary— E4F1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 130 VUS of 157 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.35Z-score

OE missense 0.83 (0.77–0.90)

424 obs / 509.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.15–0.48)

0≤0.351.4

Missense OE?0.83 (0.77–0.90)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 8 / 30.3Missense obs/exp: 424 / 509.5Syn Z: -2.39

This gene — mechanism propensity

0.6259th %ile

GOF

0.4282th %ile

LOF

0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

157 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS130

Likely Benign9

Likely Pathogenic

130

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	1	0	1
VUS	130	0	130
Likely Benign	7	2	9
Benign	0	0	0
Total	138	2	140

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 51) ClinVar copy-number / structural variants overlap E4F1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →