Reviewed September 2010
What is the official name of the IKBKG gene?
The official name of this gene is “inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma.”
IKBKG is the gene's official symbol. The IKBKG gene is also known by other names, listed below.
What is the normal function of the IKBKG gene?
The IKBKG gene (also known as NEMO) provides instructions for making a protein that plays a critical role in regulating nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins (a protein complex) that binds to DNA and controls the activity of other genes.
Within cells, the IKBKG protein interacts with two enzymes, IKK-alpha and IKK-beta, to activate nuclear factor-kappa-B. The activated factor then moves into the nucleus and binds to DNA. Nuclear factor-kappa-B regulates the activity of multiple genes, including genes that control the body's immune responses and inflammatory reactions. It also protects the cell from certain signals that would otherwise cause it to self-destruct (undergo apoptosis).
How are changes in the IKBKG gene related to health conditions?
- incontinentia pigmenti - caused by mutations in the IKBKG gene
More than 30 mutations in the IKBKG gene have been identified in people with incontinentia pigmenti. The most common mutation, a complex rearrangement that deletes some genetic material from the IKBKG gene, accounts for more than 80 percent of all cases of the condition. This mutation probably leads to the production of an abnormally small, nonfunctional version of the IKBKG protein. Other people with incontinentia pigmenti have mutations that prevent the production of any IKBKG protein. Without this protein, nuclear factor-kappa-B cannot be activated. Cells without active nuclear factor-kappa-B are more sensitive to signals that trigger them to self-destruct. The resulting abnormal cell death likely leads to the signs and symptoms of incontinentia pigmenti.
- osteopetrosis - caused by mutations in the IKBKG gene
Several mutations in the IKBKG gene have been found to cause a rare form of osteopetrosis with an X-linked pattern of inheritance. Researchers often refer to this condition as OL-EDA-ID, an acronym derived from each of the major features of the disorder. In addition to the abnormally dense bones characteristic of osteopetrosis, OL-EDA-ID is associated with abnormal swelling caused by a buildup of fluid (lymphedema) and a condition called anhydrotic ectodermal dysplasia that affects the skin, hair, teeth, and sweat glands. Affected individuals also have a malfunctioning immune system (immunodeficiency), which allows severe, recurrent infections to develop.
The mutations responsible for OL-EDA-ID impair the normal function of the IKBKG protein, which reduces activation of nuclear factor-kappa-B. These changes disrupt certain signaling pathways within immune cells, resulting in immunodeficiency. It is unclear how IKBKG mutations lead to the other features of OL-EDA-ID, although the signs and symptoms are likely caused by abnormal nuclear factor-kappa-B signaling in other types of cells.
- other disorders - caused by mutations in the IKBKG gene
Mutations in the IKBKG gene have also been identified in people, usually males, with other conditions affecting the skin, hair, teeth, and nails. These mutations reduce but do not eliminate the function of the IKBKG protein. For example, mutations in this gene have been shown to cause a disorder called hypohidrotic ectodermal dysplasia with immune deficiency (EDA-ID), which is characterized by missing or abnormal teeth, an inability to sweat, and recurrent serious infections.
IKBKG mutations also account for some cases of a condition known as X-linked susceptibility to mycobacterial disease. People with this condition have an increased risk of infection with forms of bacteria called mycobacteria. Some of these foreign invaders do not cause disease in healthy people but can cause lung disease and other medical problems in those with an increased susceptibility to infection. Another type of mycobacterium causes tuberculosis, a respiratory disease that can be serious or life-threatening. The IKBKG mutations responsible for X-linked susceptibility to mycobacterial disease alter the structure of the IKBKG protein. The defective protein disrupts certain signaling pathways within immune cells, which prevents the immune system from defending the body effectively against mycobacterial infection.
Where is the IKBKG gene located?
Cytogenetic Location: Xq28
Molecular Location on the X chromosome: base pairs 153,770,458 to 153,793,260
The IKBKG gene is located on the long (q) arm of the X chromosome at position 28.
More precisely, the IKBKG gene is located from base pair 153,770,458 to base pair 153,793,260 on the X chromosome.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about IKBKG?
You and your healthcare professional may find the following resources about IKBKG helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((IKBKG%5BTIAB%5D)%20OR%20(inhibitor%20of%20kappa%20light%20polypeptide%20gene%20enhancer%20in%20B-cells,%20kinase%20gamma%5BTIAB%5D))%20OR%20((FIP-3%5BTIAB%5D)%20OR%20(FIP3%5BTIAB%5D)%20OR%20(Fip3p%5BTIAB%5D)%20OR%20(IKK-gamma%5BTIAB%5D)%20OR%20(IP2%5BTIAB%5D)%20OR%20(NEMO%5BTIAB%5D)%20OR%20(NF-kappa-B%20essential%20modulator%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- ATYPICAL MYCOBACTERIOSIS, FAMILIAL, X-LINKED 1 (http://omim.org/entry/300636)
- ECTODERMAL DYSPLASIA, HYPOHIDROTIC, WITH IMMUNE DEFICIENCY (http://omim.org/entry/300291)
- INHIBITOR OF KAPPA LIGHT POLYPEPTIDE GENE ENHANCER IN B CELLS, KINASE OF, GAMMA (http://omim.org/entry/300248)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_IKBKG.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/8517)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=8517)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=5961)
What other names do people use for the IKBKG gene or gene products?
- NF-kappa-B essential modulator
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding IKBKG?
immune system ;
pattern of inheritance ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Aradhya S, Woffendin H, Jakins T, Bardaro T, Esposito T, Smahi A, Shaw C, Levy M, Munnich A, D'Urso M, Lewis RA, Kenwrick S, Nelson DL. A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations. Hum Mol Genet. 2001 Sep 15;10(19):2171-9. (http://www.ncbi.nlm.nih.gov/pubmed/11590134?dopt=Abstract)
- Berlin AL, Paller AS, Chan LS. Incontinentia pigmenti: a review and update on the molecular basis of pathophysiology. J Am Acad Dermatol. 2002 Aug;47(2):169-87; quiz 188-90. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12140463?dopt=Abstract)
- Bruckner AL. Incontinentia pigmenti: a window to the role of NF-kappaB function. Semin Cutan Med Surg. 2004 Jun;23(2):116-24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15295921?dopt=Abstract)
- DŲffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis-Girod S, Blanche S, Wood P, Rabia SH, Headon DJ, Overbeek PA, Le Deist F, Holland SM, Belani K, Kumararatne DS, Fischer A, Shapiro R, Conley ME, Reimund E, Kalhoff H, Abinun M, Munnich A, IsraŽl A, Courtois G, Casanova JL. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001 Mar;27(3):277-85. (http://www.ncbi.nlm.nih.gov/pubmed/11242109?dopt=Abstract)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/8517)
- Filipe-Santos O, Bustamante J, Haverkamp MH, Vinolo E, Ku CL, Puel A, Frucht DM, Christel K, von Bernuth H, Jouanguy E, Feinberg J, Durandy A, Senechal B, Chapgier A, Vogt G, de Beaucoudrey L, Fieschi C, Picard C, Garfa M, Chemli J, Bejaoui M, Tsolia MN, Kutukculer N, Plebani A, Notarangelo L, Bodemer C, Geissmann F, IsraŽl A, Vťron M, Knackstedt M, Barbouche R, Abel L, Magdorf K, Gendrel D, Agou F, Holland SM, Casanova JL. X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production. J Exp Med. 2006 Jul 10;203(7):1745-59. Epub 2006 Jul 3. (http://www.ncbi.nlm.nih.gov/pubmed/16818673?dopt=Abstract)
- Fusco F, Bardaro T, Fimiani G, Mercadante V, Miano MG, Falco G, IsraŽl A, Courtois G, D'Urso M, Ursini MV. Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation. Hum Mol Genet. 2004 Aug 15;13(16):1763-73. Epub 2004 Jun 30. (http://www.ncbi.nlm.nih.gov/pubmed/15229184?dopt=Abstract)
- Gene Review: Incontinentia Pigmenti (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=i-p)
- Hay RT. Modifying NEMO. Nat Cell Biol. 2004 Feb;6(2):89-91. (http://www.ncbi.nlm.nih.gov/pubmed/14755268?dopt=Abstract)
- Orange JS, Geha RS. Finding NEMO: genetic disorders of NF-[kappa]B activation. J Clin Invest. 2003 Oct;112(7):983-5. (http://www.ncbi.nlm.nih.gov/pubmed/14523034?dopt=Abstract)
- Smahi A, Courtois G, Rabia SH, DŲffinger R, Bodemer C, Munnich A, Casanova JL, IsraŽl A. The NF-kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes. Hum Mol Genet. 2002 Oct 1;11(20):2371-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12351572?dopt=Abstract)
- Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, IsraŽl A, Heiss NS, Klauck SM, Kioschis P, Wiemann S, Poustka A, Esposito T, Bardaro T, Gianfrancesco F, Ciccodicola A, D'Urso M, Woffendin H, Jakins T, Donnai D, Stewart H, Kenwrick SJ, Aradhya S, Yamagata T, Levy M, Lewis RA, Nelson DL. Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature. 2000 May 25;405(6785):466-72. (http://www.ncbi.nlm.nih.gov/pubmed/10839543?dopt=Abstract)
- Uzel G. The range of defects associated with nuclear factor kappaB essential modulator. Curr Opin Allergy Clin Immunol. 2005 Dec;5(6):513-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16264331?dopt=Abstract)
- Verma UN, Yamamoto Y, Prajapati S, Gaynor RB. Nuclear role of I kappa B Kinase-gamma/NF-kappa B essential modulator (IKK gamma/NEMO) in NF-kappa B-dependent gene expression. J Biol Chem. 2004 Jan 30;279(5):3509-15. Epub 2003 Nov 3. (http://www.ncbi.nlm.nih.gov/pubmed/14597638?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.