NALCN

Description

The NALCN (sodium leak channel, non-selective) is a protein-coding gene located on chromosome 13.

NALCN is a voltage-gated ion channel responsible for the resting sodium permeability that controls neuronal excitability. It functions as a multi-protein complex, consisting of at least NALCN, NALF1, UNC79, and UNC80. NALCN serves as the voltage-sensing, pore-forming subunit of the complex. The NALCN channel complex is constitutively active and conducts monovalent cations, but it is blocked by physiological concentrations of extracellular divalent cations. In addition to regulating neuronal excitability, NALCN is required for normal respiratory rhythm, systemic osmoregulation by controlling serum sodium concentration, and the regulation of intestinal pace-making activity in the interstitial cells of Cajal. It is also activated by neuropeptides such as neurotensin and substance P through a SRC family kinases-dependent pathway. Furthermore, NALCN activity is enhanced or modulated by several GPCRs, such as CHRM3.

NALCN is also known as CLIFAHDD, CanIon, IHPRF, IHPRF1, INNFD, VGCNL1, bA430M15.1.

Associated Diseases

• Hypotonia-speech impairment-severe cognitive delay syndrome
• Hypotonia, infantile, with psychomotor retardation and characteristic facies 1
• Sheldon-Hall syndrome
• Distal arthrogryposis type 1
• Congenital contractures of the limbs and face, hypotonia, and developmental delay
• Freeman-Sheldon syndrome
• Congenital limbs-face contractures-hypotonia-developmental delay syndrome