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    EIF2B4 eukaryotic translation initiation factor 2B subunit delta [ Homo sapiens (human) ]

    Gene ID: 8890, updated on 5-May-2024

    Summary

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    Official Symbol
    EIF2B4provided by HGNC
    Official Full Name
    eukaryotic translation initiation factor 2B subunit deltaprovided by HGNC
    Primary source
    HGNC:HGNC:3260
    See related
    Ensembl:ENSG00000115211 MIM:606687; AllianceGenome:HGNC:3260
    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
    VWM4; EIF2B; EIF-2B; EIF2Bdelta
    Summary
    Eukaryotic initiation factor 2B (EIF2B), which is necessary for protein synthesis, is a GTP exchange factor composed of five different subunits. The protein encoded by this gene is the fourth, or delta, subunit. Defects in this gene are a cause of leukoencephalopathy with vanishing white matter (VWM) and ovarioleukodystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 20.0), prostate (RPKM 13.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    2p23.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (27364352..27370338, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (27406760..27412735, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (27587219..27593205, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene mitochondrial inner membrane protein MPV17 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:27543343-27543946 Neighboring gene Sharpr-MPRA regulatory regions 9483 and 12628 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15495 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15496 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15497 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15498 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:27545801-27546773 Neighboring gene general transcription factor IIIC subunit 2 Neighboring gene GTF3C2 antisense RNA 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancers GRCh37_chr2:27579025-27579638 and GRCh37_chr2:27579639-27580252 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:27582391-27583132 Neighboring gene GTF3C2 antisense RNA 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:27592451-27593412 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:27593413-27594374 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15506 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:27601343-27602213 Neighboring gene sorting nexin 17 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11297 Neighboring gene zinc finger protein 513 Neighboring gene protein phosphatase, Mg2+/Mn2+ dependent 1G Neighboring gene ferritin heavy chain 1 pseudogene 3

    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
    • 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. Leukodystrophy Due to eIF2B Mutations in Adults. Shivaram S, et al. Can J Neurol Sci, 2022 Sep. PMID 34663487
    2. A rare mutation in EIF2B4 gene in an epileptic child with vanishing white matter disease: a case report. Gungor O, et al. Genet Couns, 2015. PMID 26043506
    3. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response. Sidrauski C, et al. Elife, 2015 Apr 15. PMID 25875391, Free PMC Article
    4. Adult-onset vanishing white matter disease with novel missense mutations in a subunit of translational regulator, EIF2B4. Kanbayashi T, et al. Clin Genet, 2015 Oct. PMID 25600065
    5. Developmental splicing deregulation in leukodystrophies related to EIF2B mutations. Huyghe A, et al. PLoS One, 2012. PMID 22737209, Free PMC Article

    See all (109) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Leukodystrophy Due to eIF2B Mutations in Adults.
      Title: Leukodystrophy Due to eIF2B Mutations in Adults.
    2. A novel missense mutation within EIF2B4 is associated with vanishing white matter disease.
      Title: Adult-onset vanishing white matter disease with novel missense mutations in a subunit of translational regulator, EIF2B4.
    3. demonstrate that DAP5 associates with eIF2beta and eIF4AI to stimulate IRES-dependent translation of cellular mRNAs
      Title: DAP5 associates with eIF2β and eIF4AI to promote Internal Ribosome Entry Site driven translation.
    4. The functional effects of selected vanishing white matter disease mutations in EIF2B2-5 by coexpressing mutated and wild-type subunits in human cells.
      Title: Severity of vanishing white matter disease does not correlate with deficits in eIF2B activity or the integrity of eIF2B complexes.
    5. analysis of developmental splicing deregulation in leukodystrophies related to EIF2B mutations
      Title: Developmental splicing deregulation in leukodystrophies related to EIF2B mutations.
    6. A mutation .626G>A [p.Arg209Gln] in exon 7 and c.1399C>T [p.Arg467Trp] in exon 13 of the EIF2B4-Gens.
      Title: [Vanishing white matter disease: a stress-related leukodystrophy].
    7. Data demonstrate that cellular response resulting from eIF2alpha phosphorylation is attenuated in several cancer cell lines, and correlates with the expression of a specific isoform of a regulatory eIF2B subunit, eIF2Bdelta variant 1 (V1).
      Title: Regulation of the unfolded protein response by eif2Bdelta isoforms.
    8. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Use of genome-wide expression data to mine the "Gray Zone" of GWA studies leads to novel candidate obesity genes.
    9. These results validate the measurement of eIF2B GEF activity in patients' transformed-lymphocytes as an important tool for the diagnosis of eIF2B-related disorders.
      Title: Eukaryotic initiation factor 2B (eIF2B) GEF activity as a diagnostic tool for EIF2B-related disorders.
    10. A unique EIF2B mutation spectrum in Chinese Vanishing white matter patients was shown.
      Title: Identification of novel EIF2B mutations in Chinese patients with vanishing white matter disease.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    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

    EBI GWAS Catalog

    Description
    Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of eukaryotic translation initiation factor 2B, subunit 4 delta (EIF2B4, 67kDa) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Clone Names

    • DKFZp586J0119

    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 initiation factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables translation initiation factor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in T cell receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cytoplasmic translational initiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in myelination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in oligodendrocyte development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in ovarian follicle development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of translation NAS
    Non-traceable Author Statement
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    translation initiation factor eIF2B subunit delta
    Names
    eIF-2B GDP-GTP exchange factor subunit delta
    eIF2B GDP-GTP exchange factor subunit delta
    eukaryotic translation initiation factor 2B subunit 4 delta
    eukaryotic translation initiation factor 2B, subunit 4 delta, 67kDa
    translation initiation factor eIF-2B subunit delta
    translation initiation factor eIF-2b delta subunit

    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_009305.1 RefSeqGene

      Range
      5120..11106
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001034116.2 → NP_001029288.1  translation initiation factor eIF2B subunit delta isoform 2

      See identical proteins and their annotated locations for NP_001029288.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 4.
      Source sequence(s)
      AF112207, BC091502, JQ991007
      Consensus CDS
      CCDS33164.1
      UniProtKB/Swiss-Prot
      Q53RY7, Q5BJF4, Q9BUV9, Q9UBG4, Q9UI10, Q9UIQ9, Q9UJ95
      UniProtKB/TrEMBL
      Q71US4
      Related
      ENSP00000233552.6, ENST00000347454.9
      Conserved Domains (1) summary
      pfam01008
      Location:219 → 509
      IF-2B; Initiation factor 2 subunit family

    2. NM_001318965.2 → NP_001305894.1  translation initiation factor eIF2B subunit delta isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) encodes the longest isoform (4).
      Source sequence(s)
      AC074117, AF112207, BC001870, BG717490
      Consensus CDS
      CCDS82432.1
      UniProtKB/TrEMBL
      E7ERK9, Q71US4
      Related
      ENSP00000429323.1, ENST00000493344.6
      Conserved Domains (1) summary
      pfam01008
      Location:240 → 530
      IF-2B; Initiation factor 2 subunit family

    3. NM_001318966.2 → NP_001305895.1  translation initiation factor eIF2B subunit delta isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (5) is shorter at the N-terminus compared to isoform 4.
      Source sequence(s)
      AC074117, AF112207, AF218009, AK300734
      UniProtKB/TrEMBL
      Q71US4
      Conserved Domains (2) summary
      COG1184
      Location:204 → 502
      GCD2; Translation initiation factor 2B subunit, eIF-2B alpha/beta/delta family [Translation, ribosomal structure and biogenesis]
      pfam01008
      Location:204 → 494
      IF-2B; Initiation factor 2 subunit family

    4. NM_001318967.2 → NP_001305896.1  translation initiation factor eIF2B subunit delta isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence and uses an alternate in-frame splice junction compared to variant 4. The resulting isoform (6) is shorter at the N-terminus and lacks an alternate internal aa compared to isoform 4.
      Source sequence(s)
      AC074117, AF057699, AF112207, JQ991007
      UniProtKB/TrEMBL
      Q71US4
      Conserved Domains (2) summary
      COG1184
      Location:188 → 486
      GCD2; Translation initiation factor 2B subunit, eIF-2B alpha/beta/delta family [Translation, ribosomal structure and biogenesis]
      pfam01008
      Location:188 → 478
      IF-2B; Initiation factor 2 subunit family

    5. NM_001318968.2 → NP_001305897.1  translation initiation factor eIF2B subunit delta isoform 7

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) uses an alternate splice junction compared to variant 4. The resulting isoform (7) is shorter at the N-terminus compared to isoform 4.
      Source sequence(s)
      AF112207, AJ011306, BC001870, BI255289
      UniProtKB/TrEMBL
      Q9Y3W7
      Conserved Domains (2) summary
      COG1184
      Location:24 → 322
      GCD2; Translation initiation factor 2B subunit, eIF-2B alpha/beta/delta family [Translation, ribosomal structure and biogenesis]
      pfam01008
      Location:24 → 314
      IF-2B; Initiation factor 2 subunit family

    6. NM_001318969.2 → NP_001305898.1  translation initiation factor eIF2B subunit delta isoform 8

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (8) is shorter at the N-terminus compared to isoform 4.
      Source sequence(s)
      AC074117
      UniProtKB/TrEMBL
      Q9Y3W7
      Conserved Domains (1) summary
      pfam01008
      Location:13 → 303
      IF-2B; Initiation factor 2 subunit family

    7. NM_015636.4 → NP_056451.3  translation initiation factor eIF2B subunit delta isoform 3

      See identical proteins and their annotated locations for NP_056451.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence and uses an alternate in-frame splice junction compared to variant 4. The resulting isoform (3) has a shorter and distinct N-terminus and lacks an internal aa compared to isoform 4.
      Source sequence(s)
      AC074117
      Consensus CDS
      CCDS46244.1
      UniProtKB/TrEMBL
      Q71US4
      Related
      ENSP00000394397.2, ENST00000445933.6
      Conserved Domains (2) summary
      COG1184
      Location:218 → 516
      GCD2; Translation initiation factor 2B subunit, eIF-2B alpha/beta/delta family [Translation, ribosomal structure and biogenesis]
      pfam01008
      Location:218 → 508
      IF-2B; Initiation factor 2 subunit family

    8. NM_172195.4 → NP_751945.2  translation initiation factor eIF2B subunit delta isoform 1

      See identical proteins and their annotated locations for NP_751945.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) uses an alternate in-frame splice junction compared to variant 4. The resulting isoform (1, also known as the "long" isoform)) has the same N- and C-termini but is 1 aa shorter compared to isoform 4.
      Source sequence(s)
      AF112207, AJ011306, BC091502
      Consensus CDS
      CCDS46245.1
      UniProtKB/TrEMBL
      Q71US4
      Related
      ENSP00000394869.2, ENST00000451130.6
      Conserved Domains (2) summary
      COG1184
      Location:239 → 537
      GCD2; Translation initiation factor 2B subunit, eIF-2B alpha/beta/delta family [Translation, ribosomal structure and biogenesis]
      pfam01008
      Location:239 → 529
      IF-2B; Initiation factor 2 subunit family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      27364352..27370338 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      27406760..27412735 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UI10.2 GenPept UniProtKB/Swiss-Prot:Q9UI10

    Gene LinkOut

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

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