FN1 gene

At least three mutations in the FN1 gene have been found to cause fibronectin glomerulopathy, a progressive kidney disease that usually begins in adulthood and results in irreversible kidney failure (end-stage renal disease). FN1 gene mutations account for about 40 percent of cases of fibronectin glomerulopathy. The FN1 gene mutations change single protein building blocks (amino acids) in the fibronectin-1 protein. One mutation that occurs in multiple families replaces the amino acid tyrosine with the amino acid cysteine at position 973 in the fibronectin-1 protein (written as Tyr973Cys or Y973C). FN1 gene mutations impair the protein's ability to bind to cells and proteins. The unbound fibronectin-1 protein, specifically soluble plasma fibronectin-1, is deposited in the glomeruli of the kidneys. These structures are clusters of tiny blood vessels in the kidneys that filter waste products from blood, which are then released in urine. Even though there is an abundance of fibronectin-1 in the glomeruli, the extracellular matrix that supports the blood vessels is weak because the altered fibronectin-1 cannot assist in the matrix's continual formation. Without a strong cellular support network, the glomeruli are less able to filter waste. As a result, products that normally are retained by the body, such as protein and blood, get released in the urine, and acids are not properly filtered from the blood. Over time, the kidneys' ability to filter waste decreases until the kidneys can no longer function, resulting in end-stage renal disease.