EIF4E

eukaryotic translation initiation factor 4E

Basic information

Region (hg38): 4:98879275-98929133

Previous symbols: [ "EIF4EL1", "EIF4F" ]

Links

ENSG00000151247 ∙ NCBI:1977 ∙ OMIM:133440 ∙ HGNC:3287 ∙ Uniprot:P06730 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, 19 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autism, susceptibility to, 19	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	19556253

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF4E gene.

• Inborn genetic diseases (6 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF4E 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			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding				1		1
Total	0	0	6	1	0

Variants in EIF4E

This is a list of pathogenic ClinVar variants found in the EIF4E region.

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

Position	Type	Phenotype	Significance	ClinVar
4-98881101-A-G		not specified	Uncertain significance (Aug 14, 2023)
4-98881149-GA-G			Benign (Nov 30, 2017)
4-98881149-G-GA			Benign (Dec 31, 2019)
4-98884959-T-A		not specified	Uncertain significance (Jun 02, 2023)
4-98886531-T-C			Likely benign (Dec 31, 2019)
4-98887103-G-A		EIF4E-related disorder	Benign (Oct 17, 2019)
4-98887152-C-A		not specified	Uncertain significance (Apr 11, 2023)
4-98891271-T-C		not specified	Uncertain significance (Nov 10, 2022)
4-98901903-T-C		not specified	Uncertain significance (Sep 22, 2023)
4-98901916-C-T		not specified	Uncertain significance (Jan 26, 2022)
4-98928975-A-G		EIF4E-related disorder	Benign (Oct 17, 2019)
4-98929085-C-A		EIF4E-related disorder	Likely benign (Apr 29, 2019)
4-98929100-C-T		not specified	Uncertain significance (Feb 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF4E	protein_coding	protein_coding	ENST00000505992	8	58954

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.941	0.0587	125643	0	1	125644	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	48	131	0.366	0.00000687	1630
Missense in Polyphen		5	26.971	0.18539		399
Synonymous	0.632	40	45.4	0.881	0.00000245	446
Loss of Function	3.47	2	17.8	0.112	0.00000107	189

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap. {ECO:0000269|PubMed:16271312, ECO:0000269|PubMed:22578813}.
• Disease: DISEASE: Autism 19 (AUTS19) [MIM:615091]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. {ECO:0000269|PubMed:19556253}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A heterozygous single-nucleotide insertion has been found in families affected by autism. The variant results in increased promoter activity and is involved in disease pathogenesis through EIF4E deregulation (PubMed:19556253). {ECO:0000269|PubMed:19556253}.; DISEASE: Note=A chromosomal aberration involving EIF4E has been found in a patient with classic autism. Translocation t(45)(q23q31.3). The breakpoint on chromosome 4 is located 56 kb downstream of EIF4E (PubMed:19556253). {ECO:0000269|PubMed:19556253}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);RNA transport - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Leucine Stimulation on Insulin Signaling;TGF-Ncore;EGF-Ncore;Translation Factors;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Leptin signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;JAK-STAT;Structural Pathway of Interleukin 1 (IL-1);Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Insulin Signaling;Hypertrophy Model;Interferon type I signaling pathways;Signal Transduction;mtor signaling pathway;regulation of eif-4e and p70s6 kinase;skeletal muscle hypertrophy is regulated via akt-mtor pathway;internal ribosome entry pathway;Translation initiation complex formation;Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S;Cytokine Signaling in Immune system;Alpha6Beta4Integrin;Eukaryotic Translation Initiation;Translation;Metabolism of proteins;mTORC1-mediated signalling;mTOR signalling;Metabolism of RNA;Immune System;Transport of the SLBP independent Mature mRNA;Transport of the SLBP Dependant Mature mRNA;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Mature mRNAs Derived from Intronless Transcripts;insulin Mam;eukaryotic protein translation;IL2;Ribosomal scanning and start codon recognition;L13a-mediated translational silencing of Ceruloplasmin expression;Leptin;IL6;GTP hydrolysis and joining of the 60S ribosomal subunit;Cap-dependent Translation Initiation;Deadenylation of mRNA;Deadenylation-dependent mRNA decay;mTOR signaling pathway;Signaling mediated by p38-alpha and p38-beta;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Validated targets of C-MYC transcriptional activation;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA;TSLP;insulin (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.937
• hipred: Y
• hipred_score: 0.783
• ghis: 0.711

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Eif4e
• Phenotype: cellular phenotype; neoplasm

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;behavioral fear response;RNA export from nucleus;mRNA export from nucleus;translational initiation;regulation of translation;negative regulation of autophagy;viral process;negative regulation of translation;stem cell population maintenance;lung development;negative regulation of neuron differentiation;positive regulation of mitotic cell cycle;cellular response to dexamethasone stimulus;regulation of translation at postsynapse, modulating synaptic transmission
• Cellular component: P-body;cytoplasm;cytosol;mRNA cap binding complex;cytoplasmic stress granule;eukaryotic translation initiation factor 4F complex;RISC complex;chromatoid body;cytoplasmic ribonucleoprotein granule;perinuclear region of cytoplasm;extracellular exosome;glutamatergic synapse;postsynaptic cytosol
• Molecular function: RNA cap binding;RNA 7-methylguanosine cap binding;RNA binding;translation initiation factor activity;protein binding;enzyme binding;eukaryotic initiation factor 4G binding;translation regulator activity;repressing transcription factor binding