EIF6 Gene

Name	eukaryotic translation initiation factor 6
Description	Hemidesmosomes are structures which link the basal lamina to the intermediate filament cytoskeleton. An important functional component of hemidesmosomes is the integrin beta-4 subunit (ITGB4), a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and prevent the association of the 40S and 60S ribosomal subunits. Multiple non-protein coding transcript variants and variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Eukaryotic initiation factor 6 (eIF6) is a multifunctional protein that plays a central role in controlling ribosome dynamics and mRNA translation. By binding to the 60S ribosomal subunit, eIF6 acts as an anti‐association factor that prevents premature 80S ribosome formation, thereby ensuring that ribosome joining occurs only under appropriate conditions (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Its removal from the 60S subunit—a critical step for translational activation—is mediated by cofactors such as SBDS and the GTPase EFL1, as demonstrated by structural and functional studies that also link defective eIF6 release to ribosomopathies like Shwachman-Diamond syndrome (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In addition to its pivotal role in ribosome maturation, eIF6 is essential for efficient initiation of translation in vivo and functions as a rate-limiting mediator that translates extracellular signals—such as insulin or growth factors—into increased protein synthesis (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": " Moreover, eIF6 has been implicated in microRNA-mediated post-transcriptional silencing, as its incorporation into ribonucleoprotein complexes is required for robust miRNA function, although this role may vary with the organism (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " eIF6 subcellular distribution is dynamically regulated through phosphorylation and dephosphorylation events—modulating its trafficking between the nucleus and cytoplasm—and it can form specific complexes (for example with BCCIPβ) that further influence its activity in ribosome biogenesis (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Importantly, overexpression of eIF6 is observed in several human cancers, where its heightened activity drives aberrant translation that promotes tumor growth, alterations in metabolic pathways (including enhanced lipogenesis and glycolysis), and progression of liver and lung malignancies; conversely, reduction of eIF6 activity delays tumorigenesis and ameliorates metabolic dysfunction (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marcello Ceci, Cristina Gaviraghi, Chiara Gorrini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature02160"}], "href": "https://doi.org/10.1038/nature02160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14654845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14654845"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Andrew J Finch, Christine Hilcenko, Nicolas Basse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.623011"}], "href": "https://doi.org/10.1101/gad.623011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21536732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21536732"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Félix Weis, Emmanuel Giudice, Mark Churcher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of eIF6 release from the nascent 60S ribosomal subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.3112"}], "href": "https://doi.org/10.1038/nsmb.3112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26479198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26479198"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Polina Stepensky, Montserrat Chacón-Flores, Katherine H Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "EFL1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": ", an "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SBDS"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in aShwachman-Diamond like syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2016-104366"}], "href": "https://doi.org/10.1136/jmedgenet-2016-104366"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28331068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28331068"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shengjiang Tan, Laëtitia Kermasson, Christine Hilcenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Somatic genetic rescue of a germline ribosome assembly defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-24999-5"}], "href": "https://doi.org/10.1038/s41467-021-24999-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34413298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34413298"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Valentina Gandin, Annarita Miluzio, Anna Maria Barbieri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature07267"}], "href": "https://doi.org/10.1038/nature07267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18784653"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18784653"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Annarita Miluzio, Anne Beugnet, Stefano Grosso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impairment of cytoplasmic eIF6 activity restricts lymphomagenesis and tumor progression without affecting normal growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2011.04.018"}], "href": "https://doi.org/10.1016/j.ccr.2011.04.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21665150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21665150"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nadine Gantenbein, Eva Bernhart, Ines Anders, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Influence of eukaryotic translation initiation factor 6 on non-small cell lung cancer development and progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Cancer (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejca.2018.07.001"}], "href": "https://doi.org/10.1016/j.ejca.2018.07.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30077122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30077122"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alessandra Scagliola, Annarita Miluzio, Gabriele Ventura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting of eIF6-driven translation induces a metabolic rewiring that reduces NAFLD and the consequent evolution to hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-25195-1"}], "href": "https://doi.org/10.1038/s41467-021-25195-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34385447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34385447"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Thimmaiah P Chendrimada, Kenneth J Finn, Xinjun Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA silencing through RISC recruitment of eIF6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature05841"}], "href": "https://doi.org/10.1038/nature05841"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17507929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17507929"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Richard J Flavin, Paul C Smyth, Stephen P Finn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mod Pathol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/modpathol.2008.33"}], "href": "https://doi.org/10.1038/modpathol.2008.33"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18327211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18327211"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Arunima Biswas, Shaeri Mukherjee, Supratik Das, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic shuttling of mammalian translation initiation factor eIF6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.188565"}], "href": "https://doi.org/10.1074/jbc.M110.188565"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21084295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21084295"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Emanuel Wyler, Franziska Wandrey, Lukas Badertscher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2014.08.013"}], "href": "https://doi.org/10.1016/j.febslet.2014.08.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25150171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25150171"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Daniela Brina, Annarita Miluzio, Sara Ricciardi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms9261"}], "href": "https://doi.org/10.1038/ncomms9261"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26383020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26383020"}]}]}]}
Synonyms	P27BBP, EIF-6, ITGB4BP, P27(BBP), EIF3A, B(2)GCN
Proteins	IF6_HUMAN
NCBI Gene ID	3692
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EIF6 has 9,114 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 130 datasets.

Click the + buttons to view associations for EIF6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EIF6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by EIF6 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of EIF6 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of EIF6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of EIF6 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of EIF6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of EIF6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of EIF6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving EIF6 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of EIF6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of EIF6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of EIF6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of EIF6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EIF6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of EIF6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EIF6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EIF6 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EIF6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EIF6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of EIF6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EIF6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EIF6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EIF6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing EIF6 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with EIF6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with EIF6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing EIF6 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of EIF6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EIF6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EIF6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EIF6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with EIF6 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of EIF6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with EIF6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with EIF6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with EIF6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with EIF6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with EIF6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EIF6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at EIF6 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EIF6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.