NIPAL4 Gene

Last updated on: 19.01.2022

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DefinitionThis section has been translated automatically.

The NIPAL4 gene (NIPAL4 is the acronym for: Non-Imprinted In Prader-Willi/Angelman Syndrome Region Protein 4 Like Domain Containing 4) is a protein-coding gene located on chromosome 5q33.3 that encodes a membrane receptor.

Diseases associated with NIPAL4 include:

Autosomal recessive congenital lamellar ichthyosis 6 (ACRI6) see below. Ichthyoses (overview)

General informationThis section has been translated automatically.

The role of NIPAL4 in skin barrier formation and the molecular mechanism of ichthyosis pathology caused by NIPAL4 mutations have not yet been fully elucidated. Animal experiments have established that Nipal4 knockout (KO) mice exhibit neonatal lethality due to skin barrier defects. Histological analysis revealed several morphological abnormalities in the Nipal4-KO epidermis, including impaired formation of lipid multilayer structures, hyperkeratosis, immature keratohyalin granules, and developed heterochromatin structures. The level of the skin barrier lipid acylceramide was decreased in Nipal4-KO mice.

The encoded NIPAL4 protein acts as a Mg(2+) transporter. Can also transport other divalent cations such as Ba(2+), Mn(2+), Sr(2+), and Co(2+), but to a much lesser extent than Mg(2+).

It was shown that the Mg2+ concentration in differentiated keratinocytes of Nipal4-KO mice was lower than that of wild-type mice. Thus, it can be concluded that low Mg2+ concentration causes disruption of proper chromatin remodeling process, which in turn leads to failure of differentiation-dependent gene induction in keratinocytes (Honda Y et al. 2018).

Furthermore, Fatp4 knockout mice (KO mice) exhibited severe skin barrier disruption and morphological abnormalities in the epidermis. The total amount of acylceramide was reduced in Fatp4-KO mice to ∼10% of wild-type mice. Decreased amounts and shortened chain lengths were observed in saturated non-acyl ceramides (Yamamoto H et al. 2020).

LiteratureThis section has been translated automatically.

  1. Honda Y et al (2018) Decreased Skin Barrier Lipid Acylceramide and Differentiation-Dependent Gene Expression in Ichthyosis Gene Nipal4-Knockout Mice. J Invest Dermatol 138:741-749.
  2. Lugassy J et al (2008) Rapid detection of homozygous mutations in congenital recessive ichthyosis. Arch Derm Res 300: 81-85.
  3. Sayeb M et al. (2019) A Tunisian family with a novel mutation in the gene CYP4F22 for lamellar ichthyosis and co-occurrence of hearing loss in a child due to mutation in the SLC26A4 gene. Int J Dermatol 58:1439-1443.
  4. Yamamoto H et al. (2020) Skin permeability barrier formation by the ichthyosis-causative gene FATP4 through formation of the barrier lipid ω-O-acylceramide. Proc Natl Acad Sci U S A. 117: 2914-2922.

Last updated on: 19.01.2022