ALOX12B Gene

The ALOX12B gene (ALOX12B is the acronym for "arachidonate 12-lipoxygenase, type 12R") is a protein-coding gene located on chromosome 17p13.1. The ALOX12B gene encodes the enzyme arachidonate 12-lipoxygenase, type 12R, which is involved in the conversion of arachidonic acid to 12R-hydroxyeicosatetraenoic acid.

Diseases associated with ALOX12B include the following variants of autosomal recessive congenital ichthyoses:

• Lamellar ichthyosis/congenital ichthyosiform erythroderma with mutation in ALOX12B (OMIM: 242100) (see Congenital autosomal recessive ichthyoses below).
• Self improving congenital ichthyosis (SICI) (OMIM:242100)

Related pathways of the encoded protein include immune response, the IL-23 pathway, and arachidonic acid metabolism.

Lipoxygenases (LOXs) catalyze the oxidation of polyunsaturated fatty acids such as arachidonic acid (AA). AA is released from cell membranes by phospholipases such as phospholipase A1 and is a response to various cytokines, polypeptides, and growth factors. The ALOX12 gene encodes arachidonic acid 12-lipoxygenase. The ALOX12 enzyme specifically catalyzes the addition of molecular oxygen to arachidonic acid to produce a biologically active lipid medium, such as 12-hydroxyeicosatetraenoic acid. 12-HETE is an important signaling molecule involved in inflammation, immune cell recruitment, vasoconstriction, and neurological function. ALOX12 metabolizes mainly arachidonic acid to 12S-hydroperoxyeicosatetraenoic acid (12(S)-HpETE) and further reduces it to 12(S)-HETE [10] by peroxyglutathione. ALOX12 is widely distributed in various cell types. Since ALOX12 functions to regulate platelet aggregation, cell migration and tumor cell proliferation, it is mainly involved in the development of diseases such as thrombosis, atherosclerosis and cancer. ALOX12 is also involved in the regulation of inflammation and apoptosis.

In the skin, ALOX12B acts upstream of ALOXE3 on the lineolate portion of esterified omega-hydroxyacyl sphingosine (EOS) ceramides to generate an epoxyketone derivative. This is a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins. Arachidonate 12-lipoxygenase, type 12R therefore plays a critical role in the synthesis of the lipid envelope of corneocytes and in the establishment of the skin barrier against water loss . It may also play a role in regulating the expression of airway mucins.

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.