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    EIF2B3 eukaryotic translation initiation factor 2B subunit gamma [ Homo sapiens (human) ]

    Gene ID: 8891, updated on 14-Nov-2024

    Summary

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    Official Symbol
    EIF2B3provided by HGNC
    Official Full Name
    eukaryotic translation initiation factor 2B subunit gammaprovided by HGNC
    Primary source
    HGNC:HGNC:3259
    See related
    Ensembl:ENSG00000070785 MIM:606273; AllianceGenome:HGNC:3259
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    VWM3; EIF-2B; EIF2Bgamma
    Summary
    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]
    Expression
    Ubiquitous expression in fat (RPKM 9.9), testis (RPKM 8.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See EIF2B3 in Genome Data Viewer
    Location:
    1p34.1
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (44850522..44986595, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (44721756..44858197, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (45316194..45452267, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancers GRCh37_chr1:45284771-45285427 and GRCh37_chr1:45285428-45286084 Neighboring gene uncharacterized LOC107984952 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:45286741-45287398 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:45287399-45288054 Neighboring gene RNA, U5E small nuclear 6, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:45301586-45302086 Neighboring gene patched 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 822 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:45341567-45342238 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:45342239-45342910 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:45342911-45343582 Neighboring gene MPRA-validated peak197 silencer Neighboring gene RNA, 5S ribosomal pseudogene 47 Neighboring gene cyclin B1 interacting protein 1 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 956 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:45452269-45452850 Neighboring gene mitochondrial ribosomal protein S17 pseudogene 1 Neighboring gene peptidylprolyl isomerase A pseudogene 35

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Fifteen novel EIF2B1-5 mutations identified in Chinese children with leukoencephalopathy with vanishing white matter and a long term follow-up. Zhang H, et al. PLoS One, 2015. PMID 25761052, Free PMC Article
    2. Endoplasmic reticulum stress intolerance in EIF2B3 mutant oligodendrocytes is modulated by depressed autophagy. Chen N, et al. Brain Dev, 2016 May. PMID 26625702
    3. Adult-onset vanishing white matter disease due to a novel EIF2B3 mutation. La Piana R, et al. Arch Neurol, 2012 Jun. PMID 22312164, Free PMC Article
    4. Adult-onset leukoencephalopathies with vanishing white matter with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5. Matsukawa T, et al. Neurogenetics, 2011 Aug. PMID 21484434
    5. Identification of eIF2Bgamma and eIF2gamma as cofactors of hepatitis C virus internal ribosome entry site-mediated translation using a functional genomics approach. Kruger M, et al. Proc Natl Acad Sci U S A, 2000 Jul 18. PMID 10900014, Free PMC Article

    See all (91) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Eif2b3 mutants recapitulate phenotypes of vanishing white matter disease and validate novel disease alleles in zebrafish.
      Title: Eif2b3 mutants recapitulate phenotypes of vanishing white matter disease and validate novel disease alleles in zebrafish.
    2. To determine the tolerance differences to ERS, cell viability and apoptosis rates were detected in oligodendrocyte cell lines transfected with EIF2B3-c.1037T>C or the wild type. We confirmed that oligodendrocytes with mutant EIF2B3 was less tolerant to ERS than the wild type, with decreased cell viability and increased apoptosis rates.
      Title: Endoplasmic reticulum stress intolerance in EIF2B3 mutant oligodendrocytes is modulated by depressed autophagy.
    3. Results show significant higher incidence of Chinese patients with EIF2B3 mutations compared with Caucasian patients. The c.1037T>C in EIF2B3 was confirmed to be a founder mutation in Chinese explaining the genotypic differences between ethnicities.
      Title: Fifteen novel EIF2B1-5 mutations identified in Chinese children with leukoencephalopathy with vanishing white matter and a long term follow-up.
    4. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    5. Observational study of gene-disease association. (HuGE Navigator)
      Title: No evidence that polymorphisms of the vanishing white matter disease genes are risk factors in multiple sclerosis.
    6. Study reports 9 novel mutations in EIF2B genes in 8 patients, increasing number of known mutations to more than 120. Using homology modeling, analyzed the impact of novel mutations on the 5 subunits of eIF2B protein (alpha, beta, gamma, delta, epsilon)
      Title: Genetic and clinical heterogeneity in eIF2B-related disorder.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to guanyl-nucleotide exchange factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables guanyl-nucleotide exchange factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to guanyl-nucleotide exchange factor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    contributes_to translation factor activity, RNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to translation initiation factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in T cell receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cytoplasmic translational initiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cytoplasmic translational initiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in oligodendrocyte development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to glucose ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in response to heat ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in response to heat TAS
    Traceable Author Statement
    more info
    		  
    involved_in response to peptide hormone ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in translational initiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    part_of eukaryotic translation initiation factor 2B complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of eukaryotic translation initiation factor 2B complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of guanyl-nucleotide exchange factor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    translation initiation factor eIF2B subunit gamma
    Names
    eIF-2B GDP-GTP exchange factor subunit gamma
    eIF2B GDP-GTP exchange factor subunit gamma
    eukaryotic translation initiation factor 2B, subunit 3 gamma, 58kDa
    translation initiation factor eIF-2B subunit gamma

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_015864.1 RefSeqGene

      Range
      5095..141168
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166588.3 → NP_001160060.1  translation initiation factor eIF2B subunit gamma isoform 2

      See identical proteins and their annotated locations for NP_001160060.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' end compared to variant 1, and encodes a shorter isoform (2) with a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AK024006, AL834288, AW972575, DA162797
      Consensus CDS
      CCDS53313.1
      UniProtKB/Swiss-Prot
      Q9NR50
      Related
      ENSP00000361257.3, ENST00000372183.7
      Conserved Domains (3) summary
      cd04198
      Location:3 → 212
      eIF-2B_gamma_N; The N-terminal domain of gamma subunit of the eIF-2B is a subfamily of glycosyltransferase 2
      COG1208
      Location:4 → 399
      GCD1; NDP-sugar pyrophosphorylase, includes eIF-2Bgamma, eIF-2Bepsilon, and LPS biosynthesis proteins [Translation, ribosomal structure and biogenesis, Cell wall/membrane/envelope biogenesis]
      cl00160
      Location:357 → 401
      LbetaH; Left-handed parallel beta-Helix (LbetaH or LbH) domain: The alignment contains 5 turns, each containing three imperfect tandem repeats of a hexapeptide repeat motif (X-[STAV]-X-[LIV]-[GAED]-X). Proteins containing hexapeptide repeats are often enzymes ...

    2. NM_001261418.2 → NP_001248347.1  translation initiation factor eIF2B subunit gamma isoform 3

      See identical proteins and their annotated locations for NP_001248347.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks the penultimate exon compared to variant 1. The resulting protein (isoform 3) is shorter compared to isoform 1.
      Source sequence(s)
      AL136380, BC018728
      Consensus CDS
      CCDS72775.1
      UniProtKB/Swiss-Prot
      Q9NR50
      Related
      ENSP00000483996.1, ENST00000620860.4
      Conserved Domains (3) summary
      cd04198
      Location:3 → 212
      eIF-2B_gamma_N; The N-terminal domain of gamma subunit of the eIF-2B is a subfamily of glycosyltransferase 2
      COG1208
      Location:4 → 399
      GCD1; NDP-sugar pyrophosphorylase, includes eIF-2Bgamma, eIF-2Bepsilon, and LPS biosynthesis proteins [Translation, ribosomal structure and biogenesis, Cell wall/membrane/envelope biogenesis]
      cl00160
      Location:357 → 401
      LbetaH; Left-handed parallel beta-Helix (LbetaH or LbH) domain: The alignment contains 5 turns, each containing three imperfect tandem repeats of a hexapeptide repeat motif (X-[STAV]-X-[LIV]-[GAED]-X). Proteins containing hexapeptide repeats are often enzymes ...

    3. NM_020365.5 → NP_065098.1  translation initiation factor eIF2B subunit gamma isoform 1

      See identical proteins and their annotated locations for NP_065098.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AK022399, AK024006, BC018728, BF879213, DA162797, W21485
      Consensus CDS
      CCDS517.1
      UniProtKB/Swiss-Prot
      B2RBH8, D3DPZ2, Q5QP89, Q5QP90, Q8NDB5, Q8WV57, Q9H850, Q9NR50
      Related
      ENSP00000353575.2, ENST00000360403.7
      Conserved Domains (2) summary
      cd04198
      Location:3 → 212
      eIF-2B_gamma_N; The N-terminal domain of gamma subunit of the eIF-2B is a subfamily of glycosyltransferase 2
      COG1208
      Location:4 → 447
      GCD1; NDP-sugar pyrophosphorylase, includes eIF-2Bgamma, eIF-2Bepsilon, and LPS biosynthesis proteins [Translation, ribosomal structure and biogenesis, Cell wall/membrane/envelope biogenesis]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      44850522..44986595 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047433500.1 → XP_047289456.1  translation initiation factor eIF2B subunit gamma isoform X2

    2. XM_047433499.1 → XP_047289455.1  translation initiation factor eIF2B subunit gamma isoform X1

    3. XM_047433501.1 → XP_047289457.1  translation initiation factor eIF2B subunit gamma isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      44721756..44858197 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054339465.1 → XP_054195440.1  translation initiation factor eIF2B subunit gamma isoform X2

    2. XM_054339464.1 → XP_054195439.1  translation initiation factor eIF2B subunit gamma isoform X1

    3. XM_054339466.1 → XP_054195441.1  translation initiation factor eIF2B subunit gamma isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NR50.1 GenPept UniProtKB/Swiss-Prot:Q9NR50

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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