EIF4A3 Gene

HGNC Family	DEAD box polypeptides (DDX)
Name	eukaryotic translation initiation factor 4A3
Description	This gene encodes a member of the DEAD box protein family. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a nuclear matrix protein. Its amino acid sequence is highly similar to the amino acid sequences of the translation initiation factors eIF4AI and eIF4AII, two other members of the DEAD box protein family. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nEIF4A3 is a central DEAD‐box RNA helicase that forms the core of the exon junction complex (EJC) by binding to spliced messenger RNAs in a sequence‐independent manner. Structural and biochemical studies have demonstrated that EIF4A3 engages directly with the phosphate–ribose backbone of RNA, and in complex with partners such as MAGOH–Y14 and MLN51 it clamps onto RNA in a pre‐hydrolysis state. In addition, phosphorylation of specific residues modulates its RNA and protein interactions during the cell cycle. These foundational studies establish EIF4A3 as an essential scaffold for the subsequent recruitment of proteins that influence mRNA metabolism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its structural role in the EJC, EIF4A3 is critical for post‐splicing mRNA surveillance. It functions as an anchor for key factors in nonsense‐mediated mRNA decay (NMD) and has been implicated in the spatial regulation of specific transcripts, for example during mRNA localization in Drosophila germ cells. In human cells, EIF4A3 contributes to the degradation of transcripts harboring premature termination codons, thereby influencing cell fate decisions in specialized tissues such as neurons and muscle, where its dysregulation has been linked to aberrant synaptic signaling and muscular dystrophies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEIF4A3 also coordinates multiple facets of RNA metabolism beyond splicing and NMD. It facilitates the recruitment of mRNA export factors to nascent transcripts, thereby linking splicing to nucleo‐cytoplasmic transport. Moreover, EIF4A3 is involved in the regulation of internal ribosome entry and the formation of stress granules, and it interfaces with various circular RNAs and long noncoding RNAs. Such interactions influence the stability, alternative processing, and translational control of target mRNAs. For instance, binding of EIF4A3 by specific circRNAs has been shown to modulate cell‐cycle regulators and autophagic responses, highlighting its multifaceted role in post‐transcriptional gene regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nProper levels and precise regulation of EIF4A3 are essential during development. Mutations or repeat expansions in its regulatory regions lead to disorders such as Richieri‐Costa–Pereira syndrome, which is characterized by craniofacial and limb malformations. In addition, haploinsufficiency of EIF4A3 impairs neural progenitor mitosis and survival, resulting in abnormal neurogenesis. These findings underscore its critical role during embryonic and cortical development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of EIF4A3 function is also intimately connected with oncogenesis. In several cancers—including colorectal, hepatocellular, and lung adenocarcinoma—alterations in EIF4A3 expression or its recruitment by oncogenic noncoding RNAs modulate cell-cycle regulators and signal transduction pathways (such as PI3K/AKT/mTOR). 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"}, {"type": "b", "children": [{"type": "t", "text": "LINC00667 promotes the proliferation, migration, and pathological angiogenesis in non-small cell lung cancer through stabilizing VEGFA by EIF4A3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbin.11361"}], "href": "https://doi.org/10.1002/cbin.11361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32281700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32281700"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Minglian Qiu, Meizhen Chen, Zhongping Lan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasmacytoma variant translocation 1 stabilized by EIF4A3 promoted malignant biological behaviors of lung adenocarcinoma by generating circular RNA LMNB2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2063666"}], "href": "https://doi.org/10.1080/21655979.2022.2063666"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35435126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35435126"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Yingqing Zhang, Weibo Qi, Yonglei Wu "}, {"type": "b", "children": [{"type": "t", "text": "EIF4A3-induced circular RNA SCAP facilitates tumorigenesis and progression of non-small-cell lung cancer via miR-7/SMAD2 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Sci Pollut Res Int (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11356-023-26307-8"}], "href": "https://doi.org/10.1007/s11356-023-26307-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37079240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37079240"}]}]}]}
Synonyms	eIF-4A-III, RCPS, MUK34, DDX48, NMP265, NUK34, eIF4A-III, EIF4AIII
Proteins	IF4A3_HUMAN
NCBI Gene ID	9775
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EIF4A3 has 10,299 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 138 datasets.

Click the + buttons to view associations for EIF4A3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EIF4A3 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 EIF4A3 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 EIF4A3 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 EIF4A3 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 EIF4A3 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 EIF4A3 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 EIF4A3 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 EIF4A3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of EIF4A3 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 EIF4A3 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 EIF4A3 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 EIF4A3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EIF4A3 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 EIF4A3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EIF4A3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EIF4A3 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 EIF4A3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EIF4A3 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 EIF4A3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with EIF4A3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of EIF4A3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing EIF4A3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EIF4A3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EIF4A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EIF4A3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing EIF4A3 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 EIF4A3 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 EIF4A3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing EIF4A3 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of EIF4A3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EIF4A3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EIF4A3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EIF4A3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of EIF4A3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with EIF4A3 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 EIF4A3 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 EIF4A3 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 EIF4A3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EIF4A3 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 EIF4A3 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 EIF4A3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.