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IKBKG inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [ Homo sapiens (human) ]

Gene ID: 8517, updated on 3-Nov-2024

Summary

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Official Symbol
IKBKGprovided by HGNC
Official Full Name
inhibitor of nuclear factor kappa B kinase regulatory subunit gammaprovided by HGNC
Primary source
HGNC:HGNC:5961
See related
Ensembl:ENSG00000269335 MIM:300248; AllianceGenome:HGNC:5961
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
IP; IP1; IP2; FIP3; IKKG; IPD2; NEMO; FIP-3; Fip3p; IMD33; SAIDX; AMCBX1; EDAID1; IKKAP1; ZC2HC9; IKK-gamma
Summary
This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Mutations in this gene result in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. A pseudogene highly similar to this locus is located in an adjacent region of the X chromosome. [provided by RefSeq, Mar 2016]
Expression
Ubiquitous expression in spleen (RPKM 11.5), appendix (RPKM 8.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See IKBKG in Genome Data Viewer
Location:
Xq28
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (154541238..154565046)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (152777621..152801428)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (153769453..153793261)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene RNA, 7SL, cytoplasmic 697, pseudogene Neighboring gene FAM3 metabolism regulating signaling molecule A Neighboring gene uncharacterized LOC124905229 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:153743824-153744447 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:153744448-153745070 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:153745046-153745202 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30065 Neighboring gene Sharpr-MPRA regulatory region 11639 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:153762224-153762818 Neighboring gene glucose-6-phosphate dehydrogenase Neighboring gene G6PD and IKBKG intron CAGE-defined low expression enhancer Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:153774097-153774640 Neighboring gene origin of replication in promoter of G6PD Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21114 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30067 Neighboring gene IKBKG recombination region Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:153792215-153792716 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:153792717-153793216 Neighboring gene IKBKG downstream recombination region Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:153798001-153798800 Neighboring gene family with sequence similarity 223 member A Neighboring gene activating transcription factor 4 pseudogene 2

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Central nervous system anomalies in 41 Chinese children incontinentia pigmenti.
    Title: Central nervous system anomalies in 41 Chinese children incontinentia pigmenti.
  2. NEMO/NF-kappaB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer.
    Title: NEMO/NF-κB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer.
  3. Familial recurrence of incontinentia pigmenti due to de novo pathogenic variants in the IKBKG gene.
    Title: Familial recurrence of incontinentia pigmenti due to de novo pathogenic variants in the IKBKG gene.
  4. Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury.
    Title: Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury.
  5. A conserved core region of the scaffold NEMO is essential for signal-induced conformational change and liquid-liquid phase separation.
    Title: A conserved core region of the scaffold NEMO is essential for signal-induced conformational change and liquid-liquid phase separation.
  6. Damaged mitochondria recruit the effector NEMO to activate NF-kappaB signaling.
    Title: Damaged mitochondria recruit the effector NEMO to activate NF-κB signaling.
  7. SARS-CoV-2 ORF3a positively regulates NF-kappaB activity by enhancing IKKbeta-NEMO interaction.
    Title: SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction.
  8. TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway.
    Title: TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway.
  9. Extracellular vesicles-transferred SBSN drives glioma aggressiveness by activating NF-kappaB via ANXA1-dependent ubiquitination of NEMO.
    Title: Extracellular vesicles-transferred SBSN drives glioma aggressiveness by activating NF-κB via ANXA1-dependent ubiquitination of NEMO.
  10. Human Genetic Diseases Linked to the Absence of NEMO: An Obligatory Somatic Mosaic Disorder in Male.
    Title: Human Genetic Diseases Linked to the Absence of NEMO: An Obligatory Somatic Mosaic Disorder in Male.
Submit: New GeneRIF Correction See all GeneRIFs (210)

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

Associated conditions

Description Tests
Anophthalmia-microphthalmia syndrome
MedGen: C5680330 GeneReviews: Not available
not available
Autoinflammatory disease, X-linked
MedGen: C5676885 OMIM: 301081 GeneReviews: Not available
not available
Ectodermal dysplasia and immunodeficiency 1
MedGen: C1846008 OMIM: 300291 GeneReviews: Not available
not available
Immunodeficiency 33
MedGen: C1970879 OMIM: 300636 GeneReviews: Not available
not available
Incontinentia pigmenti syndrome
MedGen: C0021171 OMIM: 308300 GeneReviews: Incontinentia Pigmenti
not available

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2020-11-10)

ClinGen Genome Curation PagePubMed
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2020-11-10)

ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope transmembrane glycoprotein gp41 env The HIV-1 gp41 cytoplasmic domain-induced NFkappaB activation requires TAK1, RelA, and NEMO proteins 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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables K63-linked polyubiquitin modification-dependent protein binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables K63-linked polyubiquitin modification-dependent protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables linear polyubiquitin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables polyubiquitin modification-dependent protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein domain specific binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein heterodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables signaling adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables transferrin receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA damage response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in DNA damage response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in T cell receptor signaling pathway NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in anoikis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in canonical NF-kappaB signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in canonical NF-kappaB signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in defense response to bacterium IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in establishment of vesicle localization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in immune response TAS
Traceable Author Statement
more info
 PubMed 
involved_in inflammatory response TAS
Traceable Author Statement
more info
 PubMed 
involved_in innate immune response TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of T cell receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of canonical NF-kappaB signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within positive regulation of canonical NF-kappaB signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of canonical NF-kappaB signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of macroautophagy ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of ubiquitin-dependent protein catabolic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in protein-containing complex assembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to virus TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
part_of IkappaB kinase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of IkappaB kinase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of IkappaB kinase complex IPI
Inferred from Physical Interaction
more info
 PubMed 
part_of IkappaB kinase complex TAS
Traceable Author Statement
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in mitotic spindle IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in spindle pole IDA
Inferred from Direct Assay
more info
 PubMed 
part_of ubiquitin ligase complex IPI
Inferred from Physical Interaction
more info
 PubMed 

General protein information

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Preferred Names
NF-kappa-B essential modulator
Names
14.7K (adenovirus E3 protein) interacting protein 3
I-kappa-B kinase subunit gamma
NF-kappa-B essential modifier
ikB kinase subunit gamma
ikB kinase-associated protein 1
incontinentia pigmenti
inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
inhibitor of nuclear factor kappa B kinase 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_009896.1 RefSeqGene

    Range
    5001..27803
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_70

mRNA and Protein(s)

  1. NM_001099856.6 → NP_001093326.2  NF-kappa-B essential modulator isoform b

    See identical proteins and their annotated locations for NP_001093326.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate promoter and initiates translation from an alternate in-frame upstream start codon compared to variant 1. The resulting isoform (b) has a longer N-terminus compared to isoform a.
    Source sequence(s)
    AC244090
    Consensus CDS
    CCDS48196.1
    UniProtKB/TrEMBL
    A0A087WUW6
    Related
    ENSP00000483825.1, ENST00000618670.4
    Conserved Domains (2) summary
    pfam11577
    Location:112 → 179
    NEMO; NF-kappa-B essential modulator NEMO
    pfam16516
    Location:327 → 412
    CC2-LZ; Leucine zipper of domain CC2 of NEMO, NF-kappa-B essential modulator

  2. NM_001099857.5 → NP_001093327.1  NF-kappa-B essential modulator isoform a

    See identical proteins and their annotated locations for NP_001093327.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), as well as variants 1, 3, and 7, encodes isoform a.
    Source sequence(s)
    AC244090
    Consensus CDS
    CCDS14757.1
    UniProtKB/Swiss-Prot
    Q7LBY6, Q7Z7F1, Q9Y6K9
    UniProtKB/TrEMBL
    A0A087WUW6
    Related
    ENSP00000471166.1, ENST00000594239.6
    Conserved Domains (4) summary
    TIGR02168
    Location:87 → 321
    SMC_prok_B; chromosome segregation protein SMC, common bacterial type
    pfam11577
    Location:44 → 110
    NEMO; NF-kappa-B essential modulator NEMO
    pfam18414
    Location:393 → 418
    zf_C2H2_10; C2H2 type zinc-finger
    cl15254
    Location:258 → 344
    UBAN; polyubiquitin binding domain of NEMO and related proteins

  3. NM_001145255.4 → NP_001138727.1  NF-kappa-B essential modulator isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two in-frame exons in the central coding region compared to variant 1. The resulting isoform (c) lacks two internal protein segments compared to isoform a.
    Source sequence(s)
    AC244090
    Consensus CDS
    CCDS48197.1
    UniProtKB/TrEMBL
    A0A8I5KQX5
    Related
    ENSP00000478616.1, ENST00000611176.4
    Conserved Domains (2) summary
    pfam11577
    Location:44 → 111
    NEMO; NF-kappa-B essential modulator NEMO
    cl15254
    Location:203 → 245
    UBAN; polyubiquitin binding domain of NEMO and related proteins

  4. NM_001321396.3 → NP_001308325.1  NF-kappa-B essential modulator isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1), as well as variants 3, 5, and 7, encodes isoform a.
    Source sequence(s)
    AC244090
    Consensus CDS
    CCDS14757.1
    UniProtKB/Swiss-Prot
    Q7LBY6, Q7Z7F1, Q9Y6K9
    UniProtKB/TrEMBL
    A0A087WUW6
    Conserved Domains (4) summary
    TIGR02168
    Location:87 → 321
    SMC_prok_B; chromosome segregation protein SMC, common bacterial type
    pfam11577
    Location:44 → 110
    NEMO; NF-kappa-B essential modulator NEMO
    pfam18414
    Location:393 → 418
    zf_C2H2_10; C2H2 type zinc-finger
    cl15254
    Location:258 → 344
    UBAN; polyubiquitin binding domain of NEMO and related proteins

  5. NM_001321397.3 → NP_001308326.1  NF-kappa-B essential modulator isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variant 8, encodes isoform d.
    Source sequence(s)
    AC244090
    Consensus CDS
    CCDS83513.1
    UniProtKB/TrEMBL
    A0A087X0G7, A0A087X1B1
    Related
    ENSP00000484023.1, ENST00000617207.4
    Conserved Domains (4) summary
    TIGR02169
    Location:49 → 362
    SMC_prok_A; chromosome segregation protein SMC, primarily archaeal type
    pfam11577
    Location:44 → 110
    NEMO; NF-kappa-B essential modulator NEMO
    pfam18414
    Location:392 → 417
    zf_C2H2_10; C2H2 type zinc-finger
    cl15254
    Location:257 → 343
    UBAN; polyubiquitin binding domain of NEMO and related proteins

  6. NM_001377312.1 → NP_001364241.1  NF-kappa-B essential modulator isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7), as well as variants 1, 3, and 5, encodes isoform a.
    Source sequence(s)
    AC244090
    Consensus CDS
    CCDS14757.1
    UniProtKB/Swiss-Prot
    Q7LBY6, Q7Z7F1, Q9Y6K9
    UniProtKB/TrEMBL
    A0A087WUW6
    Related
    ENSP00000394934.2, ENST00000440286.6
    Conserved Domains (4) summary
    TIGR02168
    Location:87 → 321
    SMC_prok_B; chromosome segregation protein SMC, common bacterial type
    pfam11577
    Location:44 → 110
    NEMO; NF-kappa-B essential modulator NEMO
    pfam18414
    Location:393 → 418
    zf_C2H2_10; C2H2 type zinc-finger
    cl15254
    Location:258 → 344
    UBAN; polyubiquitin binding domain of NEMO and related proteins

  7. NM_001377313.1 → NP_001364242.1  NF-kappa-B essential modulator isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variant 6, encodes isoform d.
    Source sequence(s)
    AC244090
    Consensus CDS
    CCDS83513.1
    UniProtKB/TrEMBL
    A0A087X0G7, A0A087X1B1
    Conserved Domains (4) summary
    TIGR02169
    Location:49 → 362
    SMC_prok_A; chromosome segregation protein SMC, primarily archaeal type
    pfam11577
    Location:44 → 110
    NEMO; NF-kappa-B essential modulator NEMO
    pfam18414
    Location:392 → 417
    zf_C2H2_10; C2H2 type zinc-finger
    cl15254
    Location:257 → 343
    UBAN; polyubiquitin binding domain of NEMO and related proteins

  8. NM_001377314.1 → NP_001364243.1  NF-kappa-B essential modulator isoform e

    Status: REVIEWED

    Source sequence(s)
    AC244090
    UniProtKB/TrEMBL
    A0A8I5KQX5
    Related
    ENSP00000508630.1, ENST00000689906.1
    Conserved Domains (4) summary
    cd09803
    Location:206 → 292
    UBAN; polyubiquitin binding domain of NEMO and related proteins
    pfam11577
    Location:44 → 110
    NEMO; NF-kappa-B essential modulator NEMO
    pfam18414
    Location:341 → 366
    zf_C2H2_10; C2H2 type zinc-finger
    pfam12128
    Location:44 → 185
    DUF3584; Protein of unknown function (DUF3584)

  9. NM_001377315.1 → NP_001364244.1  NF-kappa-B essential modulator isoform f

    Status: REVIEWED

    Source sequence(s)
    AC244090
    UniProtKB/TrEMBL
    A0A8I5KQX5
    Conserved Domains (3) summary
    cd09803
    Location:135 → 221
    UBAN; polyubiquitin binding domain of NEMO and related proteins
    pfam11577
    Location:44 → 110
    NEMO; NF-kappa-B essential modulator NEMO
    pfam18414
    Location:270 → 295
    zf_C2H2_10; C2H2 type zinc-finger

  10. NM_003639.4 → NP_003630.1  NF-kappa-B essential modulator isoform a

    See identical proteins and their annotated locations for NP_003630.1

    Status: REVIEWED

    Source sequence(s)
    AF062089, AF261086, BC000299
    Consensus CDS
    CCDS14757.1
    UniProtKB/Swiss-Prot
    Q7LBY6, Q7Z7F1, Q9Y6K9
    UniProtKB/TrEMBL
    A0A087WUW6
    Related
    ENSP00000479662.1, ENST00000611071.4
    Conserved Domains (4) summary
    TIGR02168
    Location:87 → 321
    SMC_prok_B; chromosome segregation protein SMC, common bacterial type
    pfam11577
    Location:44 → 110
    NEMO; NF-kappa-B essential modulator NEMO
    pfam18414
    Location:393 → 418
    zf_C2H2_10; C2H2 type zinc-finger
    cl15254
    Location:258 → 344
    UBAN; polyubiquitin binding domain of NEMO and related proteins

RNA

  1. NR_165197.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC244090

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_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    154541238..154565046
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    152777621..152801428
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y6K9.2 GenPept UniProtKB/Swiss-Prot:Q9Y6K9

Gene LinkOut

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Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous