IKBKAP

IKBKAP, also known as IκB kinase complex-associated protein and as ELP1, is a human gene that encodes the IKAP/ELP1 protein, a core subunit of the six-protein Elongator complex involved in transcriptional elongation and tRNA wobble uridine modification. The gene is widely expressed and has important roles in neural development and function.

Pathogenic variants in IKBKAP cause familial dysautonomia (FD), an autosomal recessive neurodevelopmental disorder characterized by autonomic dysfunction and sensory abnormalities. The condition is particularly prevalent among individuals of Ashkenazi Jewish descent, where carrier frequency is higher than in the general population. The most common disease-causing mutation is a splice-site variant at intron 20 (IVS20+6T>C), which leads to tissue-specific skipping of exon 20 and markedly reduced IKAP protein in the nervous system.

Diagnosis is established through clinical assessment and confirmed by genetic testing for IKBKAP variants. Management is multidisciplinary and predominantly supportive, addressing autonomic instability, feeding and growth issues, gastrointestinal motility, and airway or swallowing difficulties; there is currently no widely approved disease-modifying therapy.

Research has explored strategies to increase IKAP expression, including approaches to correct the splicing defect and the use of small molecules, but such strategies remain experimental. IKBKAP/ELP1 was historically described in relation to the IκB kinase complex, though its primary relevance today is as the gene responsible for familial dysautonomia; the condition is also known as Riley-Day syndrome.