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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EIF6
eukaryotic translation initiation factor 6
Chromosome 20 · 20q11.22
NCBI Gene: 3692Ensembl: ENSG00000242372.10HGNC: HGNC:6159UniProt: P56537
195PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolic ribosome assemblyribosome bindingextracellular exosomecytoplasmneurodegenerative diseasefrecklescancerexstrophy-epispadias complex
✦AI Summary

EIF6 (eukaryotic translation initiation factor 6) is a multifunctional regulator of ribosomal function and protein synthesis. Mechanistically, EIF6 binds to 60S ribosomal subunits and prevents their premature association with 40S subunits, thereby blocking unproductive 80S formation and regulating translation initiation 1. In the nucleus, EIF6 associates with pre-60S subunits and facilitates their maturation and export; cytoplasmic release requires RACK1-dependent protein kinase C activity 1. EIF6 plays a critical role in ribosome biogenesis and acts as a stimulatory factor for insulin/growth factor-dependent translation 1. Beyond translation, EIF6 participates in miRNA-mediated gene silencing and regulates wound healing by suppressing keratin 6B expression 2. Clinically, EIF6 dysregulation is implicated in multiple diseases. EIF6 overexpression occurs in specific human tumors, with evidence from lymphoma models showing that EIF6 depletion improves survival 1. In Shwachman-Diamond syndrome (SDS), a ribosomopathy caused by SBDS mutations, EIF6 accumulation on 60S subunits contributes to pathology; somatic EIF6 inactivation provides genetic rescue and antileukemic effects 34. In colorectal cancer, network analysis identified EIF6 as a critical therapeutic target 5. These findings position EIF6 as a key therapeutic node in cancer and inherited ribosomopathies.

Sources cited
1
EIF6 binds 60S ribosomal subunits, blocks 40S joining, is required for ribosome biogenesis and translational control, and is overexpressed in tumors with therapeutic relevance
PMID: 25252159
2
EIF6 downregulation accelerates wound healing by upregulating keratin 6B expression and promoting keratinocyte proliferation
PMID: 39406496
3
In Shwachman-Diamond syndrome, SBDS deficiency leads to eIF6 retention on 60S subunits; somatic heterozygous EIF6 inactivation provides genetic rescue with antileukemic effects
PMID: 36542827
4
Reduced EIF6 dosage attenuates TP53 pathway activation in Shwachman-Diamond syndrome models and offers insights into somatic genetic rescue mechanisms
PMID: 39964763
5
Machine learning analysis identified EIF6 as one of four critical target genes for medicinal plants against colorectal cancer
PMID: 39940699
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.15Weak
frecklesOpen Targets
0.15Weak
cancerOpen Targets
0.12Weak
exstrophy-epispadias complexOpen Targets
0.12Weak
neoplasmOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
melanomaOpen Targets
0.08Suggestive
oral squamous cell carcinomaOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
malignant pleural mesotheliomaOpen Targets
0.07Suggestive
skin neoplasmOpen Targets
0.05Suggestive
chronic ulcer of skinOpen Targets
0.05Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.05Suggestive
spinal stenosisOpen Targets
0.05Suggestive
infectionOpen Targets
0.05Suggestive
skin cancerOpen Targets
0.04Suggestive
Pituitary prolactin cell adenomaOpen Targets
0.04Suggestive
cutaneous melanomaOpen Targets
0.04Suggestive
lung cancerOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RPL38Protein interaction100%RPL27Protein interaction100%RPL29Protein interaction100%RPL32Protein interaction100%RPL31Protein interaction100%RPL3Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Brain
54%
Lung
52%
Ovary
39%
Bone Marrow
35%
Heart
28%
Gene Interaction Network
Click a node to explore
EIF6RPL38RPL27RPL29RPL32RPL31RPL3
PROTEIN STRUCTURE
Preparing viewer…
PDB8A3D · 1.67 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.62LoF Tolerant
pLIⓘ
0.65Intermediate
Observed/Expected LoF0.37 [0.23–0.62]
RankingsWhere EIF6 stands among ~20K protein-coding genes
  • #2,174of 20,598
    Most Researched195 · top quartile
  • #4,365of 17,882
    Most Constrained (LOEUF)0.62 · top quartile
Genes detectedEIF6
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Network Pharmacology and Bioinformatics Study of Six Medicinal Food Homologous Plants Against Colorectal Cancer.
PMID: 39940699
Int J Mol Sci · 2025
1.00
2
Ribosome ADP-ribosylation inhibits translation and maintains proteostasis in cancers.
PMID: 34314702
Cell · 2021
0.90
3
Biglycan fragment modulates TGF-β activity in intervertebral disc via an eIF6-coupled intracellular path.
PMID: 39951526
Sci Adv · 2025
0.80
4
Predisposition to myeloid malignancies in Shwachman-Diamond syndrome: biological insights and clinical advances.
PMID: 36542827
Blood · 2023
0.80
5
eIF6 modulates skin wound healing by upregulating keratin 6B.
PMID: 39406496
Stem Cells Transl Med · 2024
0.70