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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EIF4EBP2
eukaryotic translation initiation factor 4E binding protein 2
Chromosome 10 · 10q22.1
NCBI Gene: 1979Ensembl: ENSG00000148730.8HGNC: HGNC:3289UniProt: Q13542
59PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingtranslation repressor activitynegative regulation of translational initiationcytoplasmAlzheimer diseasetype 1 diabetes mellitusnervous system diseaseischemia
✦AI Summary

EIF4EBP2 is a translation repressor enriched in the brain that regulates eukaryotic initiation factor 4E (eIF4E) activity and plays critical roles in synaptic plasticity and memory formation 1. The protein functions through phosphorylation-dependent mechanisms: hypophosphorylated EIF4EBP2 binds eIF4E and prevents assembly of the eIF4F translation initiation complex, thereby repressing translation; conversely, hyperphosphorylated forms dissociate from eIF4E, allowing translation initiation 21. EIF4EBP2 is regulated by mTORC1 signaling, which phosphorylates it in response to growth factors and nutrient availability 34. Activity-dependent mTORC1-EIF4EBP2 signaling in hippocampal inhibitory interneurons is essential for memory formation 5. Clinically, dysregulation of EIF4EBP2 associates with cancer progression; tumor cells exploit impaired EIF4EBP2 function to enhance eIF4E-dependent translation and promote metabolic reprogramming during energetic stress 6. Additionally, EIF4EBP2 copy number variants have been identified in Ebstein anomaly, a congenital cardiac defect 7, and EIF4EBP2 emerges as a candidate biomarker in multiple sclerosis pathogenesis 8. Restoration of EIF4EBP2 function through PP2A activation shows promise for suppressing eIF4E-dependent translation in cancer therapy 9.

Sources cited
1
EIF4EBP2 represses translation initiation and regulates synaptic plasticity and memory formation
PMID: 30765518
2
Hypophosphorylated EIF4EBP2 binds eIF4E and blocks eIF4F complex assembly; hyperphosphorylated form releases eIF4E
PMID: 25533957
3
mTORC1 controls translation and mitochondrial biogenesis through 4E-BP inhibition
PMID: 24206664
4
mTORC1 regulates mitochondrial dynamics and cell survival through 4E-BP-dependent translational control
PMID: 28918902
5
4EBP1/2 promote cell survival during glucose starvation and are exploited by cancer cells; high EIF4EBP1 associates with poor cancer outcomes
PMID: 38744825
6
Activity-dependent mTORC1-4E-BP1/2 signaling in hippocampal inhibitory interneurons is essential for memory formation
PMID: 40123570
7
EIF4EBP2 copy number variants identified in Ebstein anomaly cases
PMID: 29216221
8
EIF4EBP2 identified as candidate key gene and biomarker in multiple sclerosis pathogenesis
PMID: 35339006
9
PP2A activators restore 4E-BP1/2 function to suppress eIF4E-dependent translation in cancer cells
PMID: 39869680
10
EIF4EBP2 binds eIF4E and prevents complex formation, suppressing cancer progression
PMID: 35414334
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.28Weak
type 1 diabetes mellitusOpen Targets
0.07Suggestive
nervous system diseaseOpen Targets
0.03Suggestive
ischemiaOpen Targets
0.03Suggestive
Insulin resistanceOpen Targets
0.03Suggestive
diabetes mellitusOpen Targets
0.03Suggestive
Cerebral ischemiaOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.02Suggestive
viral diseaseOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
autismOpen Targets
0.01Suggestive
neurodegenerative diseaseOpen Targets
0.01Suggestive
memory impairmentOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
obesityOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
sarcopeniaOpen Targets
0.01Suggestive
Neurodevelopmental disorderOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
HyperglycemiaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RPTORProtein interaction100%MTORProtein interaction100%EIF4G1Protein interaction95%EIF4EProtein interaction78%EIF4EBP1Protein interaction56%EIF4EBP3Protein interaction51%
Tissue Expression6 tissues
Heart
100%
Brain
96%
Lung
81%
Liver
75%
Ovary
64%
Bone Marrow
52%
Gene Interaction Network
Click a node to explore
EIF4EBP2RPTORMTOREIF4G1EIF4EEIF4EBP1EIF4EBP3
PROTEIN STRUCTURE
Preparing viewer…
PDB3AM7 · 2.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.61LoF Tolerant
pLIⓘ
0.04Tolerant
Observed/Expected LoF0.74 [0.36–1.61]
RankingsWhere EIF4EBP2 stands among ~20K protein-coding genes
  • #7,765of 20,598
    Most Researched59
  • #15,701of 17,882
    Most Constrained (LOEUF)1.61
Genes detectedEIF4EBP2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation.
PMID: 24206664
Cell Metab · 2013
1.00
2
mTOR Controls Mitochondrial Dynamics and Cell Survival via MTFP1.
PMID: 28918902
Mol Cell · 2017
0.90
3
mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism.
PMID: 38744825
Nat Commun · 2024
0.80
4
Down-regulated Circ_0000190 promotes cervical cancer by facilitating the activity of proto-oncogene protein EIF4E.
PMID: 35414334
Cell Cycle · 2022
0.70
5
Small-molecule modulators of B56-PP2A restore 4E-BP function to suppress eIF4E-dependent translation in cancer cells.
PMID: 39869680
J Clin Invest · 2025
0.60