The KRT12 gene provides instructions for making a protein called keratin 12. Keratins are a group of tough, fibrous proteins that form the structural framework of epithelial cells, which are cells that line the surfaces and cavities of the body. Keratin 12 is produced in a tissue on the surface of the eye called the corneal epithelium. This tissue forms the outermost layer of the cornea, which is the clear front covering of the eye. The corneal epithelium acts as a barrier to help prevent foreign materials, such as dust and bacteria, from entering the eye.
The keratin 12 protein partners with another keratin protein, keratin 3, to form molecules known as intermediate filaments. These filaments assemble into strong networks that provide strength and resilience to the corneal epithelium.
At least 20 mutations in the KRT12 gene have been found to cause Meesmann corneal dystrophy, an eye disease characterized by the formation of tiny cysts in the corneal epithelium.
Almost all of the KRT12 gene mutations associated with Meesmann corneal dystrophy change single protein building blocks (amino acids) in the keratin 12 protein. These changes occur in regions of the protein that are critical for the formation and stability of intermediate filaments. The altered keratin 12 protein interferes with the assembly of intermediate filaments, weakening the structural framework of the corneal epithelium. As a result, this outer layer of the cornea is abnormally fragile and develops the cysts that characterize Meesmann corneal dystrophy. The cysts likely contain clumps of abnormal keratin proteins and other cellular debris. When the cysts break open (rupture), they cause eye irritation, increased sensitivity to light (photophobia), and related symptoms.
- keratin 12, type I
- keratin, type I cytoskeletal 12