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GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EIF4B
eukaryotic translation initiation factor 4B
Chromosome 12 · 12q13.13
NCBI Gene: 1975Ensembl: ENSG00000063046.18HGNC: HGNC:3285UniProt: B4DRM3
247PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingprotein bindingnucleustranslation initiation factor activityneurodegenerative diseasehypertensiondiffuse large B-cell lymphomaRomano-Ward syndrome
✦AI Summary

EIF4B (eukaryotic translation initiation factor 4B) is a multifunctional RNA-binding protein essential for eukaryotic translation initiation. Its primary function is to promote mRNA ribosome binding by enhancing the helicase activity of EIF4A and working in association with the EIF4F complex 1. EIF4B binds near the 5'-terminal cap of mRNA and stimulates ATP-dependent RNA unwinding, facilitating ribosomal scanning of structured 5' untranslated regions 2. Beyond canonical translation initiation, EIF4B plays roles in translation termination through closed-loop mRNA structures, where it promotes eRF1 loading into the ribosomal A site 3. The protein exhibits expanded regulatory functions, including regulation of histone mRNA stability through interactions with the RNA turnover machinery 2. EIF4B dysregulation contributes to multiple cancers. In breast cancer, YTHDF3 recruits EIF4B to enhance Notch2 translation, driving epithelial-mesenchymal transition and metastasis 4. In pancreatic ductal adenocarcinoma, increased EIF4B phosphorylation via disrupted PP2A signaling elevates global mRNA translation 5. Conversely, genetically proxied EIF4B levels show protective associations with prostate cancer risk 6. Notably, elaiophylin targets EIF4B to suppress esophageal squamous cell carcinoma proliferation via the PI3K/AKT pathway 7, establishing EIF4B as a therapeutic target.

Sources cited
1
EIF4B functions with EIF4A and EIF4F as a component required for natural mRNA translation initiation
PMID: 26324716
2
EIF4B stimulates EIF4A helicase activity to promote RNA unwinding and binds extensively throughout mRNA transcripts; interacts with RNA turnover machinery including UPF1 affecting histone mRNA degradation
PMID: 39225047
3
EIF4B enhances EIF4A helicase activity and promotes translation termination through closed-loop mRNA formation by facilitating eRF1 loading
PMID: 40066881
4
YTHDF3 recruits EIF4B to promote Notch2 translation in breast cancer, driving EMT and metastasis
PMID: 39924078
5
Elaiophylin targets EIF4B to suppress esophageal squamous cell carcinoma growth via the PI3K/AKT signaling pathway
PMID: 39694222
6
EIF4B phosphorylation downstream of impaired PP2A activity enhances mRNA translation in basal pancreatic ductal adenocarcinoma
PMID: 40419509
7
Genetically proxied EIF4B levels are significantly associated with decreased prostate cancer risk
PMID: 39994764
8
EIF4B anchors to GC-rich structural elements in β-catenin 5'UTR and is required for its hypoxia-driven translation in cancer cells
PMID: 40309781
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.36Weak
hypertensionOpen Targets
0.10Weak
diffuse large B-cell lymphomaOpen Targets
0.09Suggestive
Romano-Ward syndromeOpen Targets
0.06Suggestive
viral diseaseOpen Targets
0.05Suggestive
catecholaminergic polymorphic ventricular tachycardiaOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
Alzheimer diseaseOpen Targets
0.05Suggestive
Brugada syndromeOpen Targets
0.05Suggestive
Familial short QT syndromeOpen Targets
0.05Suggestive
Familial progressive cardiac conduction defectOpen Targets
0.05Suggestive
familial atrial fibrillationOpen Targets
0.04Suggestive
sinoatrial node dysfunction and deafnessOpen Targets
0.04Suggestive
pulmonary vascular congestionOpen Targets
0.04Suggestive
atrial fibrillationOpen Targets
0.04Suggestive
cardiomyopathyOpen Targets
0.04Suggestive
Arrhythmogenic right ventricular dysplasiaOpen Targets
0.04Suggestive
familial sick sinus syndromeOpen Targets
0.04Suggestive
Wolff-Parkinson-White SyndromeOpen Targets
0.04Suggestive
atrial conduction diseaseOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EIF3IProtein interaction100%EIF3GProtein interaction100%EIF3BProtein interaction100%RPTORProtein interaction100%MTORProtein interaction100%EIF3CProtein interaction100%
Tissue Expression6 tissues
Ovary
100%
Brain
70%
Heart
51%
Lung
45%
Bone Marrow
35%
Liver
28%
Gene Interaction Network
Click a node to explore
EIF4BEIF3IEIF3GEIF3BRPTORMTOREIF3C
PROTEIN STRUCTURE
Preparing viewer…
PDB6FEC · 6.30 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.18Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.09 [0.05–0.18]
RankingsWhere EIF4B stands among ~20K protein-coding genes
  • #1,563of 20,598
    Most Researched247 · top 10%
  • #320of 17,882
    Most Constrained (LOEUF)0.18 · top 5%
Genes detectedEIF4B
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
eIF4F: a retrospective.
PMID: 26324716
J Biol Chem · 2015
1.00
2
YTHDF3 drives tumor growth and metastasis by recruiting eIF4B to promote Notch2 translation in breast cancer.
PMID: 39924078
Cancer Lett · 2025
0.90
3
Eukaryotic initiation factor 4B is a multi-functional RNA binding protein that regulates histone mRNAs.
PMID: 39225047
Nucleic Acids Res · 2024
0.80
4
Eukaryotic initiation factors eIF4F and eIF4B promote translation termination upon closed-loop formation.
PMID: 40066881
Nucleic Acids Res · 2025
0.70
5
Elaiophylin targets EIF4B to suppress the growth of esophageal squamous cell carcinoma via the PI3K/AKT signaling pathway.
PMID: 39694222
Cancer Lett · 2024
0.60