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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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See NFKBIE in Genome Data Viewer
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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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.

Chemical Information
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