NIPAL4 explained

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.^[1] NIPAL4 codes for the protein magnesium transporter NIPA4, which acts as a transporter.

Expression

NIPAL4 is mainly expressed in the skin, specifically in the granular layer of the epidermis.^[2]

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.^[3] Disruptions to this pathway results in impaired skin function, causing the symptoms of ARCI.^[4]

Pathology

Mutations in this gene account for 16% of autosomal recessive congenital ichthyosis (ARCI) cases, making it the 2nd most common gene involved with this disease.^[5] Since its first identification in 2004, 18 disease‐causing mutations have been reported in NIPAL4.

See also

• Lamellar Ichthyosis
• Congenital ichthyosiform erythroderma
• Ichthyosis
• Skin

Notes and References

1. Lefèvre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Ozguc M, Lathrop M, Prud'homme JF, Fischer J . 6 . Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis . Human Molecular Genetics . 13 . 20 . 2473–82 . October 2004 . 15317751 . 10.1093/hmg/ddh263 . free .
2. Wajid M, Kurban M, Shimomura Y, Christiano AM . NIPAL4/ichthyin is expressed in the granular layer of human epidermis and mutated in two Pakistani families with autosomal recessive ichthyosis . Dermatology . 220 . 1 . 8–14 . 2010 . 20016120 . 2855276 . 10.1159/000265757 .
3. Mauldin EA, Crumrine D, Casal ML, Jeong S, Opálka L, Vavrova K, Uchida Y, Park K, Craiglow B, Choate KA, Shin KO, Lee YM, Grove GL, Wakefield JS, Khnykin D, Elias PM . 6 . Cellular and Metabolic Basis for the Ichthyotic Phenotype in NIPAL4 (Ichthyin)-Deficient Canines . The American Journal of Pathology . 188 . 6 . 1419–1429 . June 2018 . 29548991 . 5971224 . 10.1016/j.ajpath.2018.02.008 .
4. Ballin N, Hotz A, Bourrat E, Küsel J, Oji V, Bouadjar B, Brognoli D, Hickman G, Heinz L, Vabres P, Marrakchi S, Leclerc-Mercier S, Irvine A, Tadini G, Hamm H, Has C, Blume-Peytavi U, Mitter D, Reitenbach M, Hausser I, Zimmer AD, Alter S, Fischer J . 6 . Genetical, clinical, and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4 . Human Mutation . 40 . 12 . 2318–2333 . December 2019 . 31347739 . 10.1002/humu.23883 . free .
5. Fischer J, Bourrat E . Genetics of Inherited Ichthyoses and Related Diseases . Acta Dermato-Venereologica . 100 . 7 . adv00096-196 . March 2020 . 32147747 . 10.2340/00015555-3432 . free . 9128940 .