E2F6
protein-codingE2F transcription factor 6, the group of E2F transcription factors
Gene summary
This gene encodes a member of a family of transcription factors that play a crucial role in the control of the cell cycle. The protein encoded by this gene lacks the transactivation and tumor suppressor protein association domains found in other family members, and contains a modular suppression domain that functions in the inhibition of transcription. It interacts in a complex with chromatin modifying factors. There are pseudogenes for this gene on chromosomes 22 and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.8 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 E2F6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198256.4. 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 | 0 | |||||
| missense | 31 | 1 | 32 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 3 | |||
| Total | 0 | 1 | 33 | 1 | 0 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_937987.2 | 7 | MANE Select | |
| Ensembl | ENSP00000370936.3 | 7 | MANE Select | |
| RefSeq | NP_001265204.1 | 7 | Standard | |
| RefSeq | NP_001265205.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell Cycle
- G1 to S cell cycle control
- Gene expression (Transcription)
- Transcriptional Regulation by E2F6
- Generic Transcription Pathway
Biological Process
- regulation of transcription involved in G1/S transition of mitotic cell cycle
- negative regulation of transcription by RNA polymerase II
- positive regulation of transcription by RNA polymerase II
- regulation of cell cycle
- negative regulation of G0 to G1 transition
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA binding
- DNA-binding transcription factor activity
Cellular Component
- nucleus
- nucleoplasm
- MLL1 complex
- RNA polymerase II transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381525
- Coding exons
- 7
- Length
- 21797
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125731
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.922 | 117 | 149 | 0.787 | 0.00000755 | 1819 |
| Missense (PolyPhen) | 10 | 33.311 | 0.3002 | 445 | ||
| Synonymous | -0.110 | 59 | 57.9 | 1.02 | 0.00000318 | 535 |
| Loss of Function | 2.38 | 4 | 13.4 | 0.299 | 7.16e-7 | 171 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000046 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibitor of E2F-dependent transcription. Binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3'. Has a preference for the 5'-TTTCCCGC-3' E2F recognition site. E2F6 lacks the transcriptional activation and pocket protein binding domains. Appears to regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression. May silence expression via the recruitment of a chromatin remodeling complex containing histone H3-K9 methyltransferase activity. Overexpression delays the exit of cells from the S-phase.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- LoFtool
- 0.334
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |