E2F3
protein-codingE2F transcription factor 3, the group of E2F transcription factors
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~91.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to E2F3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001949.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 39 | 2 | 2 | 43 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 42 | 3 | 2 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001940.1 | 7 | MANE Select | |
| Ensembl | ENSP00000262904.4 | 7 | MANE Select | |
| RefSeq | NP_001230005.1 | 7 | Standard | |
| Ensembl | ENSP00000443418.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Non-small cell lung cancer - Homo sapiens (human)
- Chronic myeloid leukemia - Homo sapiens (human)
- Gastric cancer - Homo sapiens (human)
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Melanoma - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- transcription initiation from RNA polymerase II promoter
- cell cycle
- positive regulation of cell population proliferation
- positive regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- proximal promoter sequence-specific DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA binding
Cellular Component
- nucleus
- nucleoplasm
- RNA polymerase II transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000346618
- Coding exons
- 7
- Length
- 91544
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125732
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.59 | 180 | 251 | 0.717 | 0.0000123 | 2963 |
| Missense (PolyPhen) | 44 | 82.7 | 0.53204 | 975 | ||
| Synonymous | 0.842 | 102 | 113 | 0.899 | 0.00000640 | 982 |
| Loss of Function | 3.50 | 2 | 18.0 | 0.111 | 9.96e-7 | 226 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.000029 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC- 3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F3 binds specifically to RB1 in a cell-cycle dependent manner. Inhibits adipogenesis, probably through the repression of CEBPA binding to its target gene promoters (By similarity). {ECO:0000250|UniProtKB:O35261}.;
Recessive Scores
- pRec
- 0.0964
Intolerance Scores
- LoFtool
- 0.289
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.18
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |