CFHR5

The CFHR5 gene provides instructions for making a protein called complement factor H-related 5. The precise function of this protein is unknown. However, its structure is similar to that of a protein called complement factor H (which is produced from the CFH gene). This similarity provides clues to the probable function of complement factor H-related 5.

Complement factor H regulates a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. This system must be carefully regulated so it targets only unwanted materials and does not attack the body's healthy cells. Complement factor H helps to protect healthy cells by preventing activation of the complement system when it is not needed. Studies suggest that complement factor H-related 5 probably plays a related role in controlling the complement system.

dense deposit disease - associated with the CFHR5 gene

Several changes in the CFHR5 gene have been associated with an increased likelihood of developing dense deposit disease. This condition, which was formerly known as membranoproliferative glomerulonephritis type II, is a form of progressive kidney (renal) disease. It is unclear how changes in the CFHR5 gene affect the function of complement factor H-related 5, and researchers are still working to determine how these genetic changes may influence disease risk.

other disorders - caused by mutations in the CFHR5 gene

At least one mutation in the CFHR5 gene has been found to cause a rare form of kidney disease called CFHR5 nephropathy, which has been identified only in people from the Mediterranean island of Cyprus. The mutation responsible for this disorder abnormally copies (duplicates) regions of the CFHR5 gene known as exons 2 and 3. This duplication changes the structure and function of complement factor H-related 5, preventing it from regulating the complement system effectively. However, it is unclear how abnormal activation of the complement system is related to the specific features of CFHR5 nephropathy.

CFHR5 gene mutations also increase the risk of developing a kidney disorder called atypical hemolytic-uremic syndrome. At least three mutations have been identified; two change single protein building blocks (amino acids) in complement factor H-related 5, while the third prevents the production of a functional version of this protein. These genetic changes lead to uncontrolled activation of the complement system. The overactive system attacks cells that line blood vessels in the kidneys, causing inflammation and the formation of abnormal blood clots. The resulting damage to the kidneys can lead to kidney failure and end-stage renal disease (ESRD). These life-threatening complications prevent the kidneys from filtering fluids and waste products from the body effectively.

Although genetic changes increase the risk of atypical hemolytic-uremic syndrome, studies suggest that they are often not sufficient to cause the disease. In people with CFHR5 gene mutations, the signs and symptoms of the disorder may be triggered by factors such as certain medications (such as anti-cancer drugs), chronic diseases, viral or bacterial infections, cancers, organ transplantation, or pregnancy.

Genetics Home Reference provides information about these additional conditions, which are also associated with changes in the CFHR5 gene:

• age-related macular degeneration
• atypical hemolytic-uremic syndrome