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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EIF4EBP3
eukaryotic translation initiation factor 4E binding protein 3
Chromosome 5 · 5q31.3
NCBI Gene: 8637Ensembl: ENSG00000243056.2HGNC: HGNC:3290UniProt: O60516
26PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
membraneprotein bindingtranslation repressor activitynegative regulation of translational initiationrestless legs syndromeattention deficit hyperactivity disorderhereditary attention deficit-hyperactivity disordercancer
✦AI Summary

EIF4EBP3 is a translational repressor that regulates translation initiation by competing with EIF4G proteins for binding to EIF4E, the cap-binding protein required for ribosome recruitment 1. In its hypophosphorylated state, EIF4EBP3 sequesters EIF4E and prevents mRNA translation; upon hyperphosphorylation, it dissociates from EIF4E, allowing translation to proceed 2. During prolonged mTORC1 inhibition, EIF4EBP3 expression is transcriptionally induced via the TFE3 transcription factor, serving as a robust biomarker of mTOR inhibitor response 2. EIF4EBP3 acts as a tumor suppressor in gastric cancer, where it is frequently downregulated through promoter methylation; overexpression inhibits cell proliferation, migration, and invasion by targeting the eIF4E/β-catenin axis 3. In cervical cancer, miR-22-3p-mediated suppression of EIF4EBP3 promotes cell proliferation and inhibits apoptosis 4. EIF4EBP3 is also a marker of CDC73 tumor suppressor haploinsufficiency in parathyroid cancer 5. Notably, elevated serum autoantibodies against EIF4EBP3 were identified as the most upregulated autoantigen in immune checkpoint inhibitor-associated myocarditis, suggesting a role in immune-related adverse events 6. These findings establish EIF4EBP3 as a critical translational regulator with multiple disease implications.

Sources cited
1
EIF4EBP3 is a translational repressor that inhibits translation by sequestering eIF4E from eIF4G
PMID: 14557257
2
EIF4EBP3 expression is induced during prolonged mTORC1 inhibition via TFE3 and serves as a biomarker of mTOR inhibitor response
PMID: 27319316
3
EIF4EBP3 is downregulated by promoter methylation in gastric cancer and acts as a tumor suppressor through the eIF4E/β-catenin axis
PMID: 31853750
4
miR-22-3p suppresses EIF4EBP3 to promote cervical cancer cell proliferation and inhibit apoptosis
PMID: 29333098
5
EIF4EBP3 is a marker of CDC73 tumor suppressor haploinsufficiency in parathyroid cancer syndrome
PMID: 22297294
6
Serum autoantibodies against EIF4EBP3 are the most upregulated autoantigen in immune checkpoint inhibitor-associated myocarditis
PMID: 39324142
Disease Associationsⓘ20
restless legs syndromeOpen Targets
0.06Suggestive
attention deficit hyperactivity disorderOpen Targets
0.06Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.05Suggestive
cancerOpen Targets
0.05Suggestive
cervical cancerOpen Targets
0.05Suggestive
schizophrenia 15Open Targets
0.05Suggestive
gastric cancerOpen Targets
0.04Suggestive
Phelan-McDermid syndromeOpen Targets
0.04Suggestive
thrombophilia due to protein C deficiency, autosomal recessiveOpen Targets
0.03Suggestive
Abnormality of the skeletal systemOpen Targets
0.03Suggestive
myocarditisOpen Targets
0.02Suggestive
biliary tract diseaseOpen Targets
0.02Suggestive
ovarian neoplasmOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.01Suggestive
cervical squamous cell carcinomaOpen Targets
0.01Suggestive
thyroid cancerOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
lymphomaOpen Targets
0.00Suggestive
viral diseaseOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
C8orf88Shared pathway100%EIF4G1Protein interaction98%EIF4E1BProtein interaction91%EIF4E3Protein interaction85%EIF4A1Protein interaction85%EIF4A2Protein interaction85%
Tissue Expression6 tissues
Heart
100%
Liver
91%
Ovary
74%
Lung
67%
Brain
31%
Bone Marrow
27%
Gene Interaction Network
Click a node to explore
EIF4EBP3C8orf88EIF4G1EIF4E1BEIF4E3EIF4A1EIF4A2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O60516
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.59LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.97 [0.61–1.59]
RankingsWhere EIF4EBP3 stands among ~20K protein-coding genes
  • #12,782of 20,598
    Most Researched26
  • #15,637of 17,882
    Most Constrained (LOEUF)1.59
Genes detectedEIF4EBP3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
MiR-22-3p Regulates Cell Proliferation and Inhibits Cell Apoptosis through Targeting the eIF4EBP3 Gene in Human Cervical Squamous Carcinoma Cells.
PMID: 29333098
Int J Med Sci · 2018
1.00
2
Autoantibody profiling of patients with immune checkpoint inhibitor-associated myocarditis: a pilot study.
PMID: 39324142
Front Immunol · 2024
0.90
3
eIF4EBP3 was downregulated by methylation and acted as a tumor suppressor by targeting eIF4E/β-catenin in gastric cancer.
PMID: 31853750
Gastric Cancer · 2020
0.80
4
Isolated oral CD30
PMID: 40903902
Mol Ther · 2025
0.70
5
Gene fusion and overlapping reading frames in the mammalian genes for 4E-BP3 and MASK.
PMID: 14557257
J Biol Chem · 2003
0.60