# NIPAL4
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{{Infobox gene}}{{short description|Gene}}
'''Nipa‐Like Domain‐Containing 4''', also known as '''''NIPAL4''''' or ''Ichthyin'', is a [gene](/source/gene) that is predicted to [code](/source/Genetic_code) for a [transmembrane protein](/source/transmembrane_protein) with nine [transmembrane domains](/source/transmembrane_domains).[{{cite journal | vauthors = Lefèvre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Ozguc M, Lathrop M, Prud'homme JF, Fischer J | display-authors = 6 | title = Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis | journal = Human Molecular Genetics | volume = 13 | issue = 20 | pages = 2473–82 | date = October 2004 | pmid = 15317751 | doi = 10.1093/hmg/ddh263 | doi-access = free | hdl = 11655/14560 | hdl-access = free }}] ''NIPAL4'' codes for the protein '''[magnesium](/source/magnesium) [transporter](/source/Membrane_transport_protein) NIPA4''', which acts as a {{chem|Mg|2+}} transporter.
== Expression ==
''NIPAL4'' is mainly expressed in the skin, specifically in the [granular layer](/source/Granular_layer_of_skin) of the [epidermis](/source/epidermis).[{{cite journal | vauthors = Wajid M, Kurban M, Shimomura Y, Christiano AM | title = NIPAL4/ichthyin is expressed in the granular layer of human epidermis and mutated in two Pakistani families with autosomal recessive ichthyosis | journal = Dermatology | volume = 220 | issue = 1 | pages = 8–14 | date = 2010 | pmid = 20016120 | pmc = 2855276 | doi = 10.1159/000265757 }}]
== Function ==
''NIPAL4'' codes for a magnesium transporter that can also transport other [divalent cation](/source/Dication)s such as Ba2+, Mn2+, Sr2+ and Co2+, though to a much less extent than Mg2+.[{{cite journal | vauthors = 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 | display-authors = 6 | title = Cellular and Metabolic Basis for the Ichthyotic Phenotype in NIPAL4 (Ichthyin)-Deficient Canines | journal = The American Journal of Pathology | volume = 188 | issue = 6 | pages = 1419–1429 | date = June 2018 | pmid = 29548991 | pmc = 5971224 | doi = 10.1016/j.ajpath.2018.02.008 }}] Disruptions to this pathway results in impaired skin function, causing the symptoms of [ARCI](/source/autosomal_recessive_congenital_ichthyosis).[{{cite journal | vauthors = 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 | display-authors = 6 | title = Genetical, clinical, and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4 | journal = Human Mutation | volume = 40 | issue = 12 | pages = 2318–2333 | date = December 2019 | pmid = 31347739 | doi = 10.1002/humu.23883 | doi-access = free }}]
== Pathology ==
Mutations in this gene account for 16% of [autosomal recessive congenital ichthyosis](/source/autosomal_recessive_congenital_ichthyosis) (ARCI) cases, making it the 2nd most common gene involved with this disease.[{{cite journal | vauthors = Fischer J, Bourrat E | title = Genetics of Inherited Ichthyoses and Related Diseases | journal = Acta Dermato-Venereologica | volume = 100 | issue = 7 | pages = adv00096-196 | date = March 2020 | pmid = 32147747 | doi = 10.2340/00015555-3432 | doi-access = free | pmc = 9128940 }}] Since its first identification in 2004, 18 disease‐causing mutations have been reported in ''NIPAL4''.