ALOXE3 Gene

The ALOXE3 gene (ALOXE3 is the acronym for "arachidonate lipoxygenase 3") is a lipoxygenase gene located on chromosome 17p13.1.

Diseases associated with ALOXE3 include the following variants of autosomal recessive congenital ichthyoses:

• Lamellar ichthyosis/congenital ichthyosiform erythroderma with mutation in ALOXE3 (OMIM: 606545) (see below Ichthyoses ).
• Self-improving congenital ichthyosis with mutation in ALOXE3 (SICI) (OMIM:606545).

Multiple transcript variants encoding different isoforms have been found for this gene. Related pathways of the encoded protein include immune response, the IL-23 pathway, and arachidonic acid metabolism.

The ALOXE3 gene belongs to the family of lipoxygenase genes. The encoded enzyme is a hydroperoxide isomerase that synthesizes a unique type of epoxy alcohol (8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid) from 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). This epoxy alcohol can activate the nuclear receptor "peroxisome proliferator-activated receptor alpha -PPARalpha-", which is involved in epidermal differentiation.

Loss of function of the encoded enzyme leads to cornification abnormalities, suggesting the function of this gene in human skin differentiation. The ALOXE3 gene is part of a cluster of lipoxygenase genes on 17p13.1.

The gene acts in the skin downstream of ALOX12B on the linolate portion of esterified omega-hydroxyacyl sphingosine (EOS) ceramides to generate an epoxyketone derivative. This step is significant in the conjugation of omega-hydroxyceramide to membrane proteins. Therefore, it plays a crucial role in the synthesis of the lipid envelope of corneocytes and in the establishment of the skin barrier against water loss (PubMed:21558561). In parallel, it may have a signaling function in barrier formation through the production of hepoxilin metabolites.

1. Anker Pet al. (2021) Report of a Novel ALOX12B Mutation in Self-Improving Collodion Ichthyosis with an Overview of the Genetic Background of the Collodion Baby Phenotype. Life (Basel) 11:624.
2. Hotz A et al. (2021) Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients. Genes (Basel) 12: 80.
3. Vahlquist A et al. (2010) Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients. J Invest Dermatol 130:438-443.