IKBKG Gene

HGNC Family	Zinc fingers
Name	inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IKBKG, which encodes the NF‐κB essential modulator (NEMO), is a critical adaptor protein that orchestrates canonical NF‐κB signaling in response to a variety of stimuli. By binding to ubiquitin chains – notably K63‐linked and linear (head‐to‐tail) polyubiquitin chains via its UBAN domain – IKBKG recruits and assembles the IκB kinase (IKK) complex, leading to phosphorylation and subsequent degradation of IκB inhibitors. This process permits NF‐κB’s nuclear translocation and activation of gene transcription programs that regulate inflammatory, anti‐apoptotic, and immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n IKBKG also serves as an integration point for signals initiated by proinflammatory cytokines (such as TNF‐α and IL‐1β), pathogen‐associated molecules, and genotoxic stress. In these contexts, post‐translational modifications including ubiquitination and sumoylation modulate its localization and activity, thereby fine‐tuning the NF‐κB response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, components of the linear ubiquitin chain assembly complex (LUBAC), such as SHARPIN and HOIL-1L, enhance IKBKG-mediated NF‐κB activation by promoting linear polyubiquitination of NEMO, underscoring its role as a ubiquitin-sensing scaffold that links upstream signaling events to activation of the IKK complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional studies in various tissues have demonstrated that IKBKG is essential for maintaining cellular and tissue homeostasis. For example, tissue specific deletion of IKBKG in intestinal epithelial cells, keratinocytes, and hepatocytes leads to chronic inflammation, defective cell survival, and even tumorigenesis, highlighting its indispensable role in protecting against excessive cell death and in preserving immune equilibrium."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies establish IKBKG as a pivotal regulatory hub that, through ubiquitin-dependent interactions and dynamic modifications, couples diverse extracellular and intracellular stress signals to the activation of NF‐κB and the maintenance of immune and cellular homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrew Kovalenko, Christine Chable-Bessia, Giuseppina Cantarella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01802"}], "href": "https://doi.org/10.1038/nature01802"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12917691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12917691"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Simin Rahighi, Fumiyo Ikeda, Masato Kawasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.03.007"}], "href": "https://doi.org/10.1016/j.cell.2009.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19303852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19303852"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhao-Hui Wu, Yuling Shi, Randal S Tibbetts, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1121513"}], "href": "https://doi.org/10.1126/science.1121513"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16497931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16497931"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fuminori Tokunaga, Tomoko Nakagawa, Masaki Nakahara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09815"}], "href": "https://doi.org/10.1038/nature09815"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21455180"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21455180"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Arianna Nenci, Christoph Becker, Andy Wullaert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epithelial NEMO links innate immunity to chronic intestinal inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature05698"}], "href": "https://doi.org/10.1038/nature05698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17361131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17361131"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Manolis Pasparakis, Gilles Courtois, Martin Hafner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature00820"}], "href": "https://doi.org/10.1038/nature00820"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12075355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12075355"}]}]}]}
Synonyms	IP2, FIP-3, IP1, AMCBX1, IKKAP1, IPD2, FIP3, IKKG, FIP3P, IKK-GAMMA, IMD33, NEMO, ZC2HC9
Proteins	NEMO_HUMAN
NCBI Gene ID	8517
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

IKBKG has 11,276 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 135 datasets.

Click the + buttons to view associations for IKBKG from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

IKBKG Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by IKBKG gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IKBKG gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of IKBKG gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of IKBKG gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of IKBKG gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of IKBKG gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IKBKG gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving IKBKG protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of IKBKG gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of IKBKG gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of IKBKG gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of IKBKG gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with IKBKG protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with IKBKG gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of IKBKG gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of IKBKG gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of IKBKG gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with IKBKG gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with IKBKG gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing IKBKG protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of IKBKG gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing IKBKG protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing IKBKG protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing IKBKG protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing IKBKG protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with IKBKG protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with IKBKG protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing IKBKG protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of IKBKG gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with IKBKG gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with IKBKG gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with IKBKG gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of IKBKG protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by IKBKG gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving IKBKG gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving IKBKG gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with IKBKG gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with IKBKG gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with IKBKG gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with IKBKG gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.