IKBKG Gene

The IKBKG gene (IKBKG stands for "Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit Gamma", also called NEMO gene) is a protein coding gene located on chromosome Xq28. The IKBKG gene encodes the regulatory subunit of the "Inhibitor of KappaB Kinase (IKK) complex", which phosphorylates inhibitors of NF-kappa-B, leading to dissociation of the inhibitor/NF-kappa-B complex, degradation of the inhibitor and activation of NF-kappaB. This activates a group of genes involved in inflammation, immunity, cell survival, and other signaling pathways.

Mutations in this gene are associated with incontinentia pigmenti (OMIM: 308300).

Furthermore, mutations are associated with the clinical picture of "An(hypo)hidrotic ectodermal dysplasia with immunodeficiency 1(OMIM: 300291), as well as with various other types of immunodeficiencies (immunodeficiency 1).

A pseudogene very similar to this locus is located in an adjacent region of the X chromosome.

1. Doffinger R et al (2001) X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappa-B signaling. Nature Genet. 27: 277-285.
2. Heller S et al (2020) T cell impairment is predictive for a severe clinical course in NEMO deficiency. J Clin Immun 40: 421-434.
3. Jain A et al . Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohidrotic ectodermal dysplasia. Nature Immun 2: 223-228.
4. Orange JS et al (2002) Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest 109: 1501-1509.
5. Orange JS et al (2004) The presentation and natural history of immunodeficiency caused by nuclear factor kappa-B essential modulator mutation. J Allergy Clin Immun 113: 725-733.
6. Roberts CML et al (2010) A novel NEMO gene mutation causing osteopetrosis, lymphoedema, hypohidrotic ectodermal dysplasia and immunodeficiency. Europ J Pediat 169: 1403-1407.
7. The International Incontinentia Pigmenti Consortium. Genomic rearrangement in NEMO impairs NF-kappa-B activation and is a cause of incontinentia pigmenti. Nature 405: 466-472.