NIPAL4

Nipa‐Like Domain‐Containing 4, also known as NIPAL4 or Ichthyin, is a gene that is predicted to code for a transmembrane protein with nine transmembrane domains. NIPAL4 codes for the protein magnesium Membrane [transport protein|transporter] NIPA4, which acts as a transporter.

Expression

NIPAL4 is mainly expressed in the skin, specifically in the granular layer of the epidermis.

Function

NIPAL4 codes for a magnesium transporter that can also transport other divalent cations such as Ba²⁺, Mn²⁺, Sr²⁺ and Co²⁺, though to a much less extent than Mg²⁺. There is also evidence that NIPAL4 is involved in the synthesis of very long chain fatty acids involved in the epidermal lipid metabolism. Disruptions to this pathway results in impaired skin function, causing the symptoms of ARCI.

Pathology

Mutations in this gene account for 16% of autosomal recessive congenital ichthyosis cases, making it the 2nd most common gene involved with this disease. Since its first identification in 2004, 18 disease‐causing mutations have been reported in NIPAL4.