EIF4E
protein-codingeukaryotic translation initiation factor 4E
Gene summary
The protein encoded by this gene is a component of the eukaryotic translation initiation factor 4F complex, which recognizes the 7-methylguanosine cap structure at the 5' end of messenger RNAs. The encoded protein aids in translation initiation by recruiting ribosomes to the 5'-cap structure. Association of this protein with the 4F complex is the rate-limiting step in translation initiation. This gene acts as a proto-oncogene, and its expression and activation is associated with transformation and tumorigenesis. Several pseudogenes of this gene are found on other chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
- EIF4EL1
- EIF4F
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0014041
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EIF4E variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001968.5. 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 | 1 | 1 | ||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 17 | 1 | 0 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001959.1 | 7 | MANE Select | |
| Ensembl | ENSP00000389624.2 | 7 | MANE Select | |
| RefSeq | NP_001124150.1 | 7 | Standard | |
| RefSeq | NP_001124151.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- G1/S transition of mitotic cell cycle
- behavioral fear response
- RNA export from nucleus
- mRNA export from nucleus
- translational initiation
Molecular Function
- RNA cap binding
- RNA 7-methylguanosine cap binding
- RNA binding
- translation initiation factor activity
- protein binding
Cellular Component
- P-body
- cytoplasm
- cytosol
- mRNA cap binding complex
- cytoplasmic stress granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000505992
- Coding exons
- 8
- Length
- 58954
- Individuals with no LoFs
- 125643
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125644
- p
- 0.00000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.58 | 48 | 131 | 0.366 | 0.00000687 | 1630 |
| Missense (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 |
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 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.388
Intolerance Scores
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |