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    NFKBIE NFKB inhibitor epsilon [ Homo sapiens (human) ]

    Gene ID: 4794, updated on 5-Mar-2024

    Summary

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    Official Symbol
    NFKBIEprovided by HGNC
    Official Full Name
    NFKB inhibitor epsilonprovided by HGNC
    Primary source
    HGNC:HGNC:7799
    See related
    Ensembl:ENSG00000146232 MIM:604548; AllianceGenome:HGNC:7799
    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
    IKBE
    Summary
    The protein encoded by this gene binds to components of NF-kappa-B, trapping the complex in the cytoplasm and preventing it from activating genes in the nucleus. Phosphorylation of the encoded protein targets it for destruction by the ubiquitin pathway, which activates NF-kappa-B by making it available to translocate to the nucleus. [provided by RefSeq, Sep 2011]
    Expression
    Broad expression in bone marrow (RPKM 9.4), spleen (RPKM 9.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    6p21.1
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (44258166..44265551, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (44092317..44099688, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (44225903..44233288, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene RNA polymerase I and III subunit C Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17260 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:44214649-44215403 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24632 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:44222709-44223424 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:44224854-44225567 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:44232415-44232914 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24633 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24634 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24635 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24636 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24637 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:44243146-44243938 Neighboring gene heat shock protein 90 alpha family class B member 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17263 Neighboring gene uncharacterized LOC124901322 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:44280829-44281388 Neighboring gene microRNA 4647 Neighboring gene solute carrier family 35 member B2 Neighboring gene transmembrane protein 151B Neighboring gene t-complex-associated-testis-expressed 1 Neighboring gene alanyl-tRNA synthetase 2, mitochondrial

    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. Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma. Mansouri L, et al. Blood, 2016 Dec 8. PMID 27670424
    2. Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children. Lundbo LF, et al. EBioMedicine, 2016 Jan. PMID 26870821, Free PMC Article
    3. Impaired NFKBIE gene function decreases cellular uptake of methotrexate by down-regulating SLC19A1 expression in a human rheumatoid arthritis cell line. Imamura H, et al. Mod Rheumatol, 2016 Jul. PMID 26587663, Free PMC Article
    4. Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway. Shain AH, et al. Nat Genet, 2015 Oct. PMID 26343386, Free PMC Article
    5. Vitamin C forestalls cigarette smoke induced NF-κB activation in alveolar epithelial cells. Das B, et al. Toxicol Lett, 2013 Jun 20. PMID 23615073

    See all (67) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.
      Title: Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma.
    2. We suggest that the impairment of NFKBIE gene function can reduce the uptake of methotrexate into cells, suggesting that the gene is an important factor for rheumatoid arthritis outcome
      Title: Impaired NFKBIE gene function decreases cellular uptake of methotrexate by down-regulating SLC19A1 expression in a human rheumatoid arthritis cell line.
    3. A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis.
      Title: Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children.
    4. results show that Gal-1 acts by inhibiting the stimulation of the LPS-induced IkappaBzeta expression, an NF-kappaB regulator involved in IL-6 gene transcription.
      Title: Galectin-1 reduced the effect of LPS on the IL-6 production in decidual cells by inhibiting LPS on the stimulation of IκBζ.
    5. Newly identified alterations included recurrent promoter mutations of NFKBIE, encoding NF-kappaB inhibitor varepsilon (IkappaBvarepsilon), in 14.5% of samples of desmoplastic melanoma
      Title: Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway.
    6. IkappaBepsilon has a role in NF-kappaB regulation in aggressive chronic lymphocytic leukemia
      Title: Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia.
    7. Vitamin C forestalls cigarette smoke induced NF-kappaB activation in alveolar epithelial cells.
      Title: Vitamin C forestalls cigarette smoke induced NF-κB activation in alveolar epithelial cells.
    8. we identified two gene loci associated with rheumatoid arthritis susceptibility- NFKBIE and RTKN2
      Title: Functional variants in NFKBIE and RTKN2 involved in activation of the NF-κB pathway are associated with rheumatoid arthritis in Japanese.
    9. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    10. Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and genetic testing. (HuGE Navigator)
      Title: Integrative predictive model of coronary artery calcification in atherosclerosis.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    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
    Functional variants in NFKBIE and RTKN2 involved in activation of the NF-κB pathway are associated with rheumatoid arthritis in Japanese.
    EBI GWAS Catalog
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    EBI GWAS Catalog
    Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.
    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

    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
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cytoplasmic sequestering of transcription factor TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in fibrillar center IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    NF-kappa-B inhibitor epsilon
    Names
    I-kappa-B-epsilon
    NF-kappa-BIE
    ikB-E
    ikB-epsilon
    ikappaBepsilon
    nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    mRNA and Protein(s)

    1. NM_004556.3 → NP_004547.3  NF-kappa-B inhibitor epsilon

      Status: REVIEWED

      Source sequence(s)
      AL139392, BC063609, U91616
      Consensus CDS
      CCDS34463.2
      UniProtKB/TrEMBL
      Q7LC14, Q96F31
      Related
      ENSP00000480216.1, ENST00000619360.6
      Conserved Domains (3) summary
      COG0666
      Location:182 → 328
      ANKYR; Ankyrin repeat [Signal transduction mechanisms]
      sd00045
      Location:231 → 261
      ANK; ANK repeat [structural motif]
      pfam12796
      Location:149 → 209
      Ank_2; Ankyrin repeats (3 copies)

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      44258166..44265551 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      44092317..44099688 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00221.3 GenPept UniProtKB/Swiss-Prot:O00221

    Gene LinkOut

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

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