E2F4

E2F transcription factor 4, the group of E2F transcription factors

Basic information

Region (hg38): 16:67192154-67198918

Links

ENSG00000205250 ∙ NCBI:1874 ∙ OMIM:600659 ∙ HGNC:3118 ∙ Uniprot:Q16254 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the E2F4 gene.

• Inborn genetic diseases (16 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the E2F4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			16			16
nonsense						0
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	0	1

Variants in E2F4

This is a list of pathogenic ClinVar variants found in the E2F4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-67192232-C-G		not specified	Uncertain significance (Jul 11, 2023)
16-67192241-G-T		not specified	Uncertain significance (Dec 17, 2023)
16-67192271-C-G		not specified	Uncertain significance (Dec 07, 2021)
16-67193079-G-A		not specified	Uncertain significance (Nov 21, 2022)
16-67193164-A-G		not specified	Uncertain significance (Aug 28, 2023)
16-67194687-G-T		not specified	Uncertain significance (Jul 14, 2021)
16-67194689-C-T		not specified	Uncertain significance (Feb 28, 2024)
16-67194798-T-A		not specified	Uncertain significance (Jan 19, 2022)
16-67194801-C-A		not specified	Uncertain significance (Jan 19, 2022)
16-67194806-C-T		not specified	Uncertain significance (Jan 19, 2022)
16-67194888-C-G		not specified	Uncertain significance (Sep 29, 2023)
16-67194893-C-T		not specified	Uncertain significance (Apr 26, 2023)
16-67194894-G-A		not specified	Uncertain significance (Apr 25, 2022)
16-67195787-G-A		not specified	Uncertain significance (Sep 14, 2022)
16-67195875-C-G		not specified	Uncertain significance (Mar 14, 2023)
16-67195890-ACAGCAG-A			Benign (Feb 01, 2023)
16-67195929-G-A		not specified	Uncertain significance (Dec 05, 2022)
16-67195997-C-A		not specified	Uncertain significance (Dec 01, 2022)
16-67197630-C-G		not specified	Uncertain significance (Feb 05, 2024)
16-67198070-G-A		not specified	Uncertain significance (Feb 15, 2023)
16-67198075-G-C		not specified	Uncertain significance (May 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
E2F4	protein_coding	protein_coding	ENST00000379378	10	6750

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.453	0.547	125741	0	6	125747	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.08	172	217	0.793	0.0000114	2653
Missense in Polyphen		25	53.164	0.47024		692
Synonymous	-1.59	105	86.2	1.22	0.00000481	829
Loss of Function	3.15	4	18.7	0.214	8.95e-7	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.00	0.00
Finnish	0.0000478	0.0000462
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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. E2F4 binds with high affinity to RBL1 and RBL2. In some instances can also bind RB1. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis. {ECO:0000250|UniProtKB:Q6DE14, ECO:0000269|PubMed:7958924, ECO:0000269|PubMed:7958925}.
• Pathway: TGF-beta signaling pathway - Homo sapiens (human);Cell cycle - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Cell Cycle;Adipogenesis;TGF-beta Signaling Pathway;G1 to S cell cycle control;Signal Transduction;Gene expression (Transcription);mets affect on macrophage differentiation;Generic Transcription Pathway;RNA Polymerase II Transcription;Transcription of E2F targets under negative control by DREAM complex;Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1;G0 and Early G1;Cyclin D associated events in G1;G1 Phase;SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription;Mitotic G1-G1/S phases;TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;TP53 Regulates Transcription of Cell Cycle Genes;Transcriptional Regulation by TP53;Cell Cycle;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Cell Cycle, Mitotic;Regulation of retinoblastoma protein;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.298

Intolerance Scores

• loftool: 0.126
• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Haploinsufficiency Scores

• pHI: 0.875
• hipred: Y
• hipred_score: 0.783
• ghis: 0.656

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: E2f4
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; skeleton phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; taste/olfaction phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype

Gene ontology

• Biological process: regulation of transcription involved in G1/S transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;epithelial cell development;cell volume homeostasis;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;blood circulation;animal organ morphogenesis;regulation of cell population proliferation;motile cilium assembly;positive regulation of transcription by RNA polymerase II;regulation of cell cycle;centriole assembly;multi-ciliated epithelial cell differentiation
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;RNA polymerase II transcription factor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;protein domain specific binding;sequence-specific DNA binding;protein dimerization activity;promoter-specific chromatin binding