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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 transporter NIPA4, which acts as a Mg2+ transporter.

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Jun 29, 2026
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NIPAL4
Identifiers
AliasesNIPAL4, ARCI6, ICHTHYIN, ICHYN, NIPA like domain containing 4, SLC57A6
External IDsOMIM: 609383; MGI: 2444671; HomoloGene: 133769; GeneCards: NIPAL4; OMA:NIPAL4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

348938

214112

Ensembl

ENSG00000172548

ENSMUSG00000020411

UniProt

Q0D2K0

Q8BZF2

RefSeq (mRNA)

NM_001099287
NM_001172292

NM_172524

RefSeq (protein)

NP_001092757
NP_001165763

NP_766112

Location (UCSC)Chr 5: 157.46 – 157.47 MbChr 11: 46.04 – 46.06 Mb
PubMed search34
Wikidata
View/Edit HumanView/Edit Mouse

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.5 NIPAL4 codes for the protein magnesium transporter NIPA4, which acts as a Mg2+
 transporter.

Expression

NIPAL4 is mainly expressed in the skin, specifically in the granular layer of the epidermis.6

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+.5 There is also evidence that NIPAL4 is involved in the synthesis of very long chain fatty acids involved in the epidermal lipid metabolism.7 Disruptions to this pathway results in impaired skin function, causing the symptoms of ARCI.8

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.9 Since its first identification in 2004, 18 disease‐causing mutations have been reported in NIPAL4.8

See also

See also

References

References

  1. GRCh38: Ensembl release 89: ENSG00000172548 – Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000020411 – Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Lefèvre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Ozguc M, et al. (October 2004). "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. doi:10.1093/hmg/ddh263. hdl:11655/14560. PMID 15317751.
  6. Wajid M, Kurban M, Shimomura Y, Christiano AM (2010). "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. doi:10.1159/000265757. PMC 2855276. PMID 20016120.
  7. Mauldin EA, Crumrine D, Casal ML, Jeong S, Opálka L, Vavrova K, et al. (June 2018). "Cellular and Metabolic Basis for the Ichthyotic Phenotype in NIPAL4 (Ichthyin)-Deficient Canines". The American Journal of Pathology. 188 (6): 1419–1429. doi:10.1016/j.ajpath.2018.02.008. PMC 5971224. PMID 29548991.
  8. Ballin N, Hotz A, Bourrat E, Küsel J, Oji V, Bouadjar B, et al. (December 2019). "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. doi:10.1002/humu.23883. PMID 31347739.
  9. Fischer J, Bourrat E (March 2020). "Genetics of Inherited Ichthyoses and Related Diseases". Acta Dermato-Venereologica. 100 (7): adv00096-196. doi:10.2340/00015555-3432. PMC 9128940. PMID 32147747.