IKBKAP

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IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) is a human gene that provides instructions to make the IKAP protein, which is found in a variety of cells throughout the body, including brain cells. Although the exact function of the IKAP protein is not clearly understood, it probably plays a role in transcription, which is the process of making a blueprint of a gene for protein production. Researchers have identified the IKAP protein as part of a six-protein complex (called the holo-elongator complex) that interacts with enzymes necessary for transcription. The IKAP protein probably performs other functions in the cell as well, such as responding to stress.

The IKBKAP gene is located on the long (q) arm of chromosome 9 at position 31, from base pair 108,709,355 to base pair 108,775,950.

[edit] Related conditions

Familial dysautonomia is caused by mutations in the IKBKAP gene. Nearly all individuals with familial dysautonomia have two copies of the same mutation in each cell, which causes part of the IKBKAP gene to be skipped during transcription. (This alteration is often called exon skipping.) This skipping mutation results in a decreased amount of IKAP protein in their cells. This mutation, however, behaves inconsistently. As a result, some cells produce near normal amounts of IKAP protein, and other cells (particularly cells in the nervous system) have very little IKAP protein.

In a small number of reported familial dysautonomia cases, researchers have identified other mutations that cause a change in amino acids (the building blocks of proteins). In these cases, arginine is replaced by proline at position 696 in the IKAP protein's chain of amino acids (also written as Arg696Pro), or proline is replaced by leucine at position 914 (also written as Pro914Leu). People with one of these improper amino acid substitutions also have the skipping mutation. Together, these mutations cause the resulting IKAP protein to malfunction.

It is unclear how mutations in the IKBKAP gene lead to the signs and symptoms of familial dysautonomia. Critical activities in brain and nerve cells are probably disrupted by reduced amounts or the absence of functional IKAP protein.

[edit] See also

• Familial dysautonomia

[edit] References

• Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY (2001). "Familial dysautonomia is caused by mutations of the IKAP gene". Am J Hum Genet 68 (3): 753-8. PMID 11179021. 
• Axelrod FB (2004). "Familial dysautonomia". Muscle Nerve 29 (3): 352-63. PMID 14981733. 
• Cuajungco MP, Leyne M, Mull J, Gill SP, Lu W, Zagzag D, Axelrod FB, Maayan C, Gusella JF, Slaugenhaupt SA (2003). "Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia". Am J Hum Genet 72 (3): 749-58. PMID 12577200.  Full text
• Leyne M, Mull J, Gill SP, Cuajungco MP, Oddoux C, Blumenfeld A, Maayan C, Gusella JF, Axelrod FB, Slaugenhaupt SA (2003). "Identification of the first non-Jewish mutation in familial Dysautonomia". Am J Med Genet A 118 (4): 305-8. PMID 12687659. 
• Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins C, Makalowska I, Brownstein M, Krappmann D, Scheidereit C, Maayan C, Axelrod FB, Gusella JF (2001). "Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia". Am J Hum Genet 68 (3): 598-605. PMID 11179008. 
• Slaugenhaupt SA, Gusella JF (2002). "Familial dysautonomia". Curr Opin Genet Dev 12 (3): 307-11. PMID 12076674. 

This article incorporates public domain text from the Genetics Home Reference, a service of the U.S. National Library of Medicine

[edit] External links

• Mendelian Inheritance in Man (OMIM) 603722
• EntrezGene 8518
• GeneCard for IKBKAP