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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EIF4E
eukaryotic translation initiation factor 4E
Chromosome 4 · 4q23
NCBI Gene: 1977Ensembl: ENSG00000151247.13HGNC: HGNC:3287UniProt: D6RBW1
513PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTransporter
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmic ribonucleoprotein granuleperinuclear region of cytoplasmexcitatory synapseextracellular exosomeneurodegenerative diseaseautismdengue diseasebreast cancer
✦AI Summary

EIF4E (eukaryotic translation initiation factor 4E) is a key regulatory protein that controls protein synthesis by recognizing and binding the 7-methylguanosine cap structure of mRNAs, facilitating ribosome recruitment and translation initiation 1. EIF4E functions as part of the eIF4F complex and competes with translational repressors like eIF4E2 and FMRP for cap binding 23. The protein exhibits oncogenic properties when overexpressed, as increased translation is required for cell cycle progression 1. EIF4E phosphorylation by MAP kinase-interacting kinases (Mnks) regulates its activity and is implicated in cancer progression through modulation of oncogene translation 4. Recent studies demonstrate that EIF4E can be targeted by small molecule inhibitors that disrupt its interaction with eIF4G, providing potential therapeutic opportunities 5. The protein shows distinct subcellular localizations under different stress conditions, with various isoforms (eIF4E1, eIF4E2, eIF4E3) displaying differential recruitment to processing bodies and stress granules 6. In cancer contexts, EIF4E activation promotes tumorigenesis through pathways like the PRSS23-eIF4E-c-Myc axis in gastric cancer 7. Under stress conditions when canonical eIF4E1-dependent translation is inhibited, cells can utilize alternative mechanisms involving eIF3d-dependent cap recognition 8.

Sources cited
1
EIF4E binds 7-methylguanosine cap structure, mediates mRNA recruitment to ribosomes, and has oncogenic properties when overexpressed
PMID: 10216941
2
METTL16 promotes translation by sequestering eIF4E2, which competes with eIF4E for cap binding
PMID: 36840945
3
FMRP competes with eIF4G1 for binding to eIF4E at the 5' cap, mediating translational repression
PMID: 40645180
4
Mnks phosphorylate eIF4E and are implicated in transformation, tumorigenesis and tumor progression
PMID: 25450520
5
Small molecule inhibitors can disrupt eIF4E:eIF4G interaction and demonstrate target engagement in cells
PMID: 40016190
6
Different eIF4E isoforms show distinct localization patterns to processing bodies and stress granules under various stress conditions
PMID: 27578149
7
PRSS23-eIF4E-c-Myc axis promotes gastric tumorigenesis with PRSS23 interacting with eIF4E
PMID: 39920289
8
eIF3d-dependent translation serves as a major mechanism for eIF4E-independent mRNA translation under stress conditions
PMID: 39107322
Disease Associationsⓘ21
neurodegenerative diseaseOpen Targets
0.53Moderate
autismOpen Targets
0.42Moderate
dengue diseaseOpen Targets
0.37Weak
breast cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
acute myeloid leukemiaOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
melanomaOpen Targets
0.11Weak
substance-related disorderOpen Targets
0.10Weak
lung cancerOpen Targets
0.10Weak
Alzheimer diseaseOpen Targets
0.10Weak
cancerOpen Targets
0.10Weak
nasopharyngeal carcinomaOpen Targets
0.10Suggestive
acute lymphoblastic leukemiaOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.10Suggestive
chronic myelogenous leukemiaOpen Targets
0.10Suggestive
esophageal squamous cell carcinomaOpen Targets
0.09Suggestive
prostate cancerOpen Targets
0.09Suggestive
urinary bladder carcinomaOpen Targets
0.09Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.09Suggestive
Autism 19UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EIF3BProtein interaction100%DICER1Protein interaction100%TNRC6AProtein interaction100%AGO1Protein interaction100%TARBP2Protein interaction100%RPTORProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
58%
Liver
47%
Lung
41%
Ovary
37%
Heart
27%
Gene Interaction Network
Click a node to explore
EIF4EEIF3BDICER1TNRC6AAGO1TARBP2RPTOR
PROTEIN STRUCTURE
Preparing viewer…
PDB4TPW · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.09Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.00 [0.00–0.09]
RankingsWhere EIF4E stands among ~20K protein-coding genes
  • #516of 20,598
    Most Researched513 · top 5%
  • #38of 17,882
    Most Constrained (LOEUF)0.09 · top 1%
Genes detectedEIF4E
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
FMRP drives mRNP targets into translationally silenced complexes.
PMID: 40645180
Mol Cell · 2025
1.00
2
METTL16 promotes translation and lung tumorigenesis by sequestering cytoplasmic eIF4E2.
PMID: 36840945
Cell Rep · 2023
0.90
3
eIF4E-independent translation is largely eIF3d-dependent.
PMID: 39107322
Nat Commun · 2024
0.80
4
MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction.
PMID: 39145446
J Clin Invest · 2024
0.80
5
Signalling to eIF4E in cancer.
PMID: 26517881
Biochem Soc Trans · 2015
0.76