E2F1

protein-coding

E2F transcription factor 1, the group of E2F transcription factors

Gene summary

The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis. [provided by RefSeq, Jul 2008]

Previous symbols:

RBBP3

MANE transcript

NM_005225.3

Inheritance

—

ClinVar variants

U:36B:13

Top phenotype

E2F1-related disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr20:33,675,477-33,686,385

External References & Databases

Ensembl (ENSG00000101412)

Transcript & Mutation Effects

hg38 • Region Span ~10.9 kb

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GenCC 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 E2F1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 10

E2F1-related disorderTotal: 7

Prostate cancerTotal: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005225.3. 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				6 clinvar	4 clinvar	10
missense			36 clinvar	1 clinvar	2 clinvar	39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	36	7	6	49

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005225.3	RefSeq	NP_005216.1	7	MANE Select
ENST00000343380.6	Ensembl	ENSP00000345571.5	7	MANE Select
ENST00000888354.1	Ensembl	ENSP00000558413.1	7	Standard
ENST00000888354.2	Ensembl	ENSP00000558413.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
e2f1	Danio rerio	Structure: thymus Quality: increased amount abnormal

Gene / Model

Organism

Observed Phenotype

e2f1

Danio rerio

Structure: thymus

Quality: increased amount

abnormal

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

DNA damage checkpoint
regulation of transcription involved in G1/S transition of mitotic cell cycle
negative regulation of transcription by RNA polymerase II
transcription, DNA-templated
regulation of transcription, DNA-templated

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
proximal promoter sequence-specific DNA binding
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
mitochondrion
centrosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343380
Coding exons: 7
Length: 10722
Individuals with no LoFs: 125473
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125474
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.07	129	214	0.602	0.0000138	2765
Missense (PolyPhen)		30	78.781	0.3808		965
Synonymous	0.880	87	98.1	0.887	0.00000685	958
Loss of Function	3.38	0	13.3	0.00	5.67e-7	168

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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. E2F1 binds preferentially RB1 in a cell-cycle dependent manner. It can mediate both cell proliferation and TP53/p53-dependent apoptosis. Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters (PubMed:20176812). Positively regulates transcription of RRP1B (PubMed:20040599). {ECO:0000250|UniProtKB:Q61501, ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20176812, ECO:0000269|PubMed:8170954}.;

Recessive Scores

pRec: 0.791

Intolerance Scores

RVIS EVS: 0.31
RVIS percentile EVS: 72.38

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