COL4A4

The COL4A4 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 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 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 COL4A4 gene

The autosomal recessive form of Alport syndrome occurs when two copies of the COL4A4 gene in each cell are altered. Most COL4A4 mutations cause a change in the sequence of amino acids (the building blocks of proteins) in a region of the alpha4(IV) collagen chain that is critical for combining with other type IV collagen chains. Other mutations severely decrease or prevent the production of any alpha4(IV) chains 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

Thin basement membrane nephropathy is inherited in an autosomal dominant pattern, which means one copy of the altered COL4A4 gene in each cell is sufficient to cause the disorder. In the past, this condition was often called benign familial hematuria. People with thin basement membrane nephropathy typically have blood in their urine but no other symptoms or signs of kidney disease. It is unusual for this condition to lead to kidney failure.