COL4A4

The COL4A4 gene provides instructions for making one component of type IV collagen, which is a flexible protein. Specifically, this gene makes the alpha4(IV) chain of type IV collagen. This chain combines with two other types of alpha (IV) chains (the alpha3 and alpha5 chains) to make a complete type IV collagen molecule. Type IV collagen molecules attach to each other to form complex protein networks. These networks make up a large portion of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen alpha3-4-5 networks play an especially important role in the basement membranes of the kidney, inner ear, and eye.

Alport syndrome - caused by mutations in the COL4A4 gene

More than 20 mutations in the COL4A4 gene have been found to cause Alport syndrome. Most of these mutations change single protein building blocks (amino acids) in a region where the alpha4(IV) collagen chain combines with other type IV collagen chains. Other mutations in the COL4A4 gene severely decrease or prevent the production of alpha4(IV) chains. As a result, there is a serious deficiency of the type IV collagen alpha3-4-5 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.

other disorders - caused by mutations in the COL4A4 gene

Mutations in the COL4A4 gene have been found to cause thin basement membrane nephropathy. This condition typically causes people to have blood in their urine (hematuria) but no other signs or symptoms of kidney disease. In the past, this condition was often called benign familial hematuria. Thin basement membrane nephropathy rarely progresses to kidney failure.