Gene Symbol: NIPAL4
Description: NIPA like domain containing 4
Alias: ARCI6, ICHTHYIN, ICHYN, magnesium transporter NIPA4, NIPA-like protein 4, non-imprinted in Prader-Willi/Angelman syndrome region protein 4
Species: human
Products:     NIPAL4

Top Publications

  1. Lefèvre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Ozguc M, et al. Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet. 2004;13:2473-82 pubmed
    ..Six homozygous mutations including one nonsense and five missense mutations were identified in a new gene, ichthyin, on chromosome 5q33 in 23 patients from 14 consanguineous families from Algeria, Colombia, Syria and Turkey...
  2. Wang X, Shaw W, Tsang H, Reid E, O Kane C. Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules. Nat Neurosci. 2007;10:177-85 pubmed
    ..understand the functions of NIPA1, mutated in the neurodegenerative disease hereditary spastic paraplegia, and of ichthyin, mutated in autosomal recessive congenital ichthyosis, we have studied their Drosophila melanogaster ortholog, ..
  3. Mauldin E, Wang P, Evans E, Cantner C, Ferracone J, Credille K, et al. Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency. Vet Pathol. 2015;52:654-62 pubmed publisher
    ..of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 (ICHTHYIN). This protein plays a role in epidermal lipid metabolism, although the mechanism is unknown...
  4. Mauldin E, Crumrine D, Casal M, Jeong S, Opálka L, Vavrova K, et al. Cellular and Metabolic Basis for the Ichthyotic Phenotype in NIPAL4 (Ichthyin)-Deficient Canines. Am J Pathol. 2018;188:1419-1429 pubmed publisher
    ..However, the basis for the phenotype in patients with NIPAL4 (ichthyin) mutations (among the most prevalent ARCIs) remains unknown...
  5. Maier D, Mazereeuw Hautier J, Tilinca M, Cosgarea R, Jonca N. Novel mutation in NIPAL4 in a Romanian family with autosomal recessive congenital ichthyosis. Clin Exp Dermatol. 2016;41:279-82 pubmed publisher
    ..b>NIPAL4 is the second most frequently mutated ARCI gene...
  6. Li H, Vahlquist A, Torma H. Interactions between FATP4 and ichthyin in epidermal lipid processing may provide clues to the pathogenesis of autosomal recessive congenital ichthyosis. J Dermatol Sci. 2013;69:195-201 pubmed publisher
    ..Another ARCI is caused by mutations in NIPAL4, coding for ichthyin, which is proposed to be a magnesium transporter or a trans-membrane receptor...
  7. Li H, Loriè E, Fischer J, Vahlquist A, Torma H. The expression of epidermal lipoxygenases and transglutaminase-1 is perturbed by NIPAL4 mutations: indications of a common metabolic pathway essential for skin barrier homeostasis. J Invest Dermatol. 2012;132:2368-2375 pubmed publisher
    ..inter alia to mutations in transglutaminase-1 (TGM1), in lipoxygenases (LOXs) of the hepoxilin pathway, and in ichthyin, a putative Mg(2+) transporter encoded by the NIPAL4 gene...
  8. Dahlqvist J, Westermark G, Vahlquist A, Dahl N. Ichthyin/NIPAL4 localizes to keratins and desmosomes in epidermis and Ichthyin mutations affect epidermal lipid metabolism. Arch Dermatol Res. 2012;304:377-86 pubmed publisher
    ..b>Ichthyin/NIPAL4 gene mutations have been identified in a subgroup of ARCI patients, but the role of ichthyin in epidermis ..
  9. Akiyama M. Updated molecular genetics and pathogenesis of ichthiyoses. Nagoya J Med Sci. 2011;73:79-90 pubmed
    ..The known causative molecules underlying ichthyosis include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F22, ichthyin and steroid sulfatase, all of which are thought to be related to the intercellular lipid layers...

More Information


  1. Kusakabe M, Nagai M, Nakano E, Jitsukawa O, Nishigori C, Yamanishi K. A Japanese Case of Ichthyosiform Erythroderma with a Novel Mutation in NIPAL4/Ichthyin. Acta Derm Venereol. 2017;97:397-398 pubmed publisher
  2. Alavi A, Shahshahani M, Klotzle B, Fan J, Ronaghi M, Elahi E. Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4. J Dermatol. 2012;39:375-81 pubmed publisher
    ..Linkage to chromosome 5 and a mutation in NIPAL4 causing p.G297R were identified...
  3. Pavez Loriè E, Gånemo A, Borgers M, Wouters L, Blockhuys S, van de Plassche L, et al. Expression of retinoid-regulated genes in lamellar ichthyosis vs. healthy control epidermis: changes after oral treatment with liarozole. Acta Derm Venereol. 2009;89:12-20 pubmed publisher
    Lamellar ichthyosis is a keratinization disorder caused by TGM1, Ichthyin and several other gene mutations...
  4. Akiyama M, Shimizu H. An update on molecular aspects of the non-syndromic ichthyoses. Exp Dermatol. 2008;17:373-82 pubmed publisher
    ..molecules underlying ichthyosis subtypes include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F2 homolog, ichthyin and steroid sulphatase and all these are thought to be related to the intercellular lipid layers...
  5. Akiyama M. Harlequin ichthyosis and other autosomal recessive congenital ichthyoses: the underlying genetic defects and pathomechanisms. J Dermatol Sci. 2006;42:83-9 pubmed
    ..The five genes are transglutaminase 1 gene (TGM1), ABCA12, two lipoxygenase genes, ALOXE3 and ALOX12B and ichthyin. One of these components, ABCA12, has recently been shown to be a keratinocyte lipid transporter associated with ..
  6. Wajid M, Kurban M, Shimomura Y, Christiano A. NIPAL4/ichthyin is expressed in the granular layer of human epidermis and mutated in two Pakistani families with autosomal recessive ichthyosis. Dermatology. 2010;220:8-14 pubmed publisher
    ..having performed a linkage analysis, we analyzed the DNA of 2 consanguineous Pakistani families with ARCI for NIPAL4 mutations and performed in situ hybridization (ISH) for NIPAL4 mRNA in the epidermis...
  7. Dahlqvist J, Klar J, Hausser I, Anton Lamprecht I, Pigg M, Gedde Dahl T, et al. Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis. J Med Genet. 2007;44:615-20 pubmed
    ..The region coincides with the ichthyin gene, previously reported as mutated in ARCI...