Elp1

Elp1, also known as ELP1 or IKBKAP, is a gene that encodes a core subunit of the Elongator protein complex. The Elongator complex consists of six subunits (ELP1–ELP6) and functions in two related cellular processes: transcriptional elongation by RNA polymerase II and the modification of wobble uridines in tRNA, which affects efficient translation of many codons. ELP1 is the largest subunit and serves as a scaffolding component that helps assemble and stabilize the complex.

Mutations in ELP1/IKBKAP cause familial dysautonomia (FD), an autosomal recessive neurodevelopmental disorder affecting the autonomic and sensory nervous systems. FD is especially prevalent among individuals of Ashkenazi Jewish descent. The most common disease-causing variant is a splice-site mutation in intron 20 (IVS20+6T>C) that reduces ELP1 expression through tissue-specific mis-splicing; other mutations include missense, nonsense, and additional splice-site changes.

Clinical features typically include lifelong autonomic dysfunction (such as blood pressure and temperature regulation problems, orthostatic intolerance, and reduced tear production) and sensory neuropathy, with gastrointestinal dysmotility, hypotonia, and variable developmental concerns. Diagnosis is established by genetic testing for ELP1/IKBKAP mutations, complemented by clinical evaluation. Management is multidisciplinary and supportive, addressing autonomic stabilization, nutrition and feeding, GI care, and respiratory support. There is currently no cure, but research continues into approaches that increase ELP1 expression or compensate for its loss, along with studies of the Elongator complex’s biological roles.