COL4A5

The COL4A5 gene carries the instructions for making one component of type IV collagen, which is a flexible protein that forms complex networks. Specifically, this gene makes the alpha5(IV) chain of type IV collagen. This chain combines with two other types of alpha (IV) chains (the alpha3 and alpha4 chains) to make a complete collagen molecule. Type IV collagen networks make up a large portion of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. This type IV collagen network plays an especially important role in the basement membranes of the kidney, inner ear, and eye.

Alport syndrome - caused by mutations in the COL4A5 gene

Mutations in the COL4A5 gene cause approximately 80 percent of Alport syndrome cases. Several hundred different mutations have been identified, the majority of which cause a change in the sequence of amino acids (the building blocks of proteins) in a region of the alpha5(IV) collagen chain that is critical for combining with other type IV collagen chains. Other mutations severely decrease or prevent the production of the alpha5(IV) chains. As a result, there is a serious deficiency of the type IV collagen network in the basement membranes of the kidney, inner ear, and eye. In the kidney, other types of collagen accumulate in the basement membranes, eventually leading to scarring of the kidneys and kidney failure. Mutations in this gene can also lead to abnormal function in the inner ear, resulting in hearing loss.