IKBKAP

IKBKAP (Inhibitor of Kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase Complex-Associated Protein) is a gene that encodes the enzyme IKAP. This enzyme is part of a complex that plays a crucial role in the transcription process of DNA into RNA. Mutations in the IKBKAP gene are associated with Familial Dysautonomia (FD), a rare genetic disorder that affects the development and survival of certain nerve cells.

Structure

The IKBKAP gene is located on the long (q) arm of chromosome 9 at position 31. The gene spans approximately 73 kilobases and comprises 37 exons. The encoded protein, IKAP, is a 150 kDa protein that is ubiquitously expressed in all tissues, with the highest levels found in the brain, heart, and muscle.

Function

IKAP is a component of the elongator complex, a multiprotein complex that associates with the RNA polymerase II enzyme and is involved in transcriptional elongation. The elongator complex also plays a role in the modification of histones, proteins that package and order the DNA into structural units called nucleosomes. These modifications can influence gene expression.

Clinical significance

Mutations in the IKBKAP gene are the primary cause of Familial Dysautonomia (FD), a disorder that affects the development and survival of sensory, sympathetic, and parasympathetic neurons. The most common mutation in individuals with FD is a point mutation in the splice site of exon 20, which leads to tissue-specific skipping of this exon and results in a truncated, nonfunctional protein.

FD is characterized by insensitivity to pain and temperature, vomiting crises, recurrent pneumonia, abnormal tear production, and more. The disease is most common in individuals of Ashkenazi Jewish descent.

See also

• Familial Dysautonomia
• Elongator complex
• RNA polymerase II
• Histone
• Nucleosome