ABCA12

The ABCA12 gene provides instructions for making a protein known as an ATP-binding cassette (ABC) transporter. ABC transporter proteins carry many types of molecules across cell membranes. In particular, the ABCA12 protein plays a major role in transporting fats (lipids) in cells that make up the outermost layer of skin (the epidermis). This lipid transport appears to be essential for normal development of the skin. The ABCA12 protein is also found in several other tissues, including the testes, placenta, lung, stomach, and fetal brain and liver.

harlequin ichthyosis - caused by mutations in the ABCA12 gene

Several mutations in the ABCA12 gene have been identified in people with harlequin ichthyosis. Most of these mutations probably lead to an absence of ABCA12 protein or the production of an extremely small version of the protein that cannot transport lipids properly. A lack of lipid transport causes numerous problems with the development of the epidermis before and after birth. Specifically, it prevents the skin from forming an effective barrier against fluid loss (dehydration) and infections, and leads to the formation of hard, thick scales characteristic of harlequin ichthyosis.

other disorders - caused by mutations in the ABCA12 gene

Mutations in the ABCA12 gene also cause a skin disorder called lamellar ichthyosis type 2. People with this disorder have red, scaly, plate-like skin covering most of their bodies. These skin abnormalities tend to be less severe than those seen with harlequin ichthyosis.

The ABCA12 mutations that cause lamellar ichthyosis type 2 change single protein building blocks (amino acids) in the ABCA12 protein. These mutations almost always alter a region of the protein that normally allows it to attach (bind) to ATP, a molecule that supplies energy for chemical reactions. These changes likely disrupt the protein's ability to transport lipids, which affects the development of the skin before and after birth.