EIF2B3 Gene

Name	eukaryotic translation initiation factor 2B, subunit 3 gamma, 58kDa
Description	The protein encoded by this gene is one of the subunits of initiation factor eIF2B, which catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. It has also been found to function as a cofactor of hepatitis C virus internal ribosome entry site-mediated translation. Mutations in this gene have been associated with leukodystrophy with vanishing white matter. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The eukaryotic translation initiation factor 2B (eIF2B) is a multisubunit complex that catalyzes the exchange of GDP for GTP on eIF2, a key step in translation initiation and regulation of the integrated stress response. In this context, EIF2B3—encoding the γ‐subunit—is critical for proper substrate recognition and contributes to a newly identified function in displacing the inhibitory factor eIF5, thereby facilitating efficient recycling of eIF2 (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mutations in EIF2B3 have been strongly implicated in vanishing white matter (VWM) disease, an autosomal recessive leukodystrophy with a variable clinical spectrum ranging from infantile to adult-onset. Studies in diverse populations have identified recurrent and founder mutations—including, for example, c.1037T>C (p.Ile346Thr) and c.260C>T (p.Ala87Val)—which impair eIF2B complex function and result in dysregulation of protein synthesis and the cellular stress response. These alterations contribute to defective myelination and white matter degeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Animal models, such as CRISPR-generated zebrafish eif2b3 mutants, together with in vitro work in oligodendrocyte cell lines, further demonstrate that loss or alteration of EIF2B3 leads to impaired autophagy and increased vulnerability to endoplasmic reticulum stress. These defects underscore the essential role of EIF2B3 in ensuring proper glial cell differentiation and maintaining white matter integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its central role in VWM disease, genetic association studies have identified EIF2B3 as a modifier of age‐at‐onset in Parkinson disease, while functional studies targeting eIF2Bγ (the EIF2B3 gene product) suggest it may also influence viral translation mechanisms, such as the IRES‐mediated initiation in hepatitis C virus infection."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight that EIF2B3 is not only pivotal for the catalytic activity of the eIF2B complex in translation initiation and stress response regulation but also plays an essential role in maintaining white matter integrity. Disruption of its function through mutation causes a cascade of cellular dysfunctions, leading to neurodegenerative pathology and altering the cellular response to stress.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrew M Bogorad, Kai Ying Lin, Assen Marintchev "}, {"type": "b", "children": [{"type": "t", "text": "Novel mechanisms of eIF2B action and regulation by eIF2α phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkx845"}], "href": "https://doi.org/10.1093/nar/gkx845"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29036434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29036434"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Martin D Jennings, Graham D Pavitt "}, {"type": "b", "children": [{"type": "t", "text": "A new function and complexity for protein translation initiation factor eIF2B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/15384101.2014.948797"}], "href": "https://doi.org/10.4161/15384101.2014.948797"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25486352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25486352"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lillian R Kenner, Aditya A Anand, Henry C Nguyen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "eIF2B-catalyzed nucleotide exchange and phosphoregulation by the integrated stress response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aaw2922"}], "href": "https://doi.org/10.1126/science.aaw2922"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31048491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31048491"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tomas Adomavicius, Margherita Guaita, Yu Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The structural basis of translational control by eIF2 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-10167-3"}], "href": "https://doi.org/10.1038/s41467-019-10167-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31086188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31086188"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Haihua Zhang, Lifang Dai, Na Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fifteen novel EIF2B1-5 mutations identified in Chinese children with leukoencephalopathy with vanishing white matter and a long term follow-up."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0118001"}], "href": "https://doi.org/10.1371/journal.pone.0118001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25761052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25761052"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lulu Xu, Meixiang Zhong, Yuyuan Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adult-onset vanishing white matter in a patient with EIF2B3 variants misdiagnosed as multiple sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10072-021-05710-4"}], "href": "https://doi.org/10.1007/s10072-021-05710-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34755279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34755279"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mehdi Khorrami, Erfan Khorram, Omid Yaghini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a Missense Variant in the EIF2B3 Gene Causing Vanishing White Matter Disease with Antenatal-Onset but Mild Symptoms and Long-Term Survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-021-01810-0"}], "href": "https://doi.org/10.1007/s12031-021-01810-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33687620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33687620"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sung Eun Hyun, Byung Se Choi, Ja-Hyun Jang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Identification of ten novel mutations in patients with eIF2B-related disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.9325"}], "href": "https://doi.org/10.1002/humu.9325"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15776425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15776425"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yu-Ri Lee, Se Hee Kim, Afif Ben-Mahmoud, et al. 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Synonyms	EIF2BGAMMA
Proteins	EI2BG_HUMAN
NCBI Gene ID	8891
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EIF2B3 has 5,921 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 121 datasets.

Click the + buttons to view associations for EIF2B3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EIF2B3 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 EIF2B3 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 EIF2B3 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 EIF2B3 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 EIF2B3 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 EIF2B3 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 EIF2B3 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 EIF2B3 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 EIF2B3 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 EIF2B3 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 EIF2B3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EIF2B3 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 EIF2B3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EIF2B3 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EIF2B3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EIF2B3 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 EIF2B3 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 EIF2B3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with EIF2B3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing EIF2B3 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 EIF2B3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EIF2B3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EIF2B3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing EIF2B3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing EIF2B3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with EIF2B3 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 EIF2B3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of EIF2B3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EIF2B3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EIF2B3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EIF2B3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving EIF2B3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving EIF2B3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with EIF2B3 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 EIF2B3 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 EIF2B3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EIF2B3 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 EIF2B3 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 EIF2B3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EIF2B3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing EIF2B3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.