|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “complement factor H.”
CFH is the gene's official symbol. The CFH gene is also known by other names, listed below.
The CFH gene provides instructions for making a protein called complement factor H. This protein helps regulate 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 an inflammatory response, 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 and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed.
The CFH gene belongs to a family of genes called complement (complement system).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
At least seven mutations in the CFH gene have been identified in people with dense deposit disease. This condition, which was formerly known as membranoproliferative glomerulonephritis type II, is a form of progressive kidney (renal) disease. Most of the CFH gene mutations that cause dense deposit disease change single protein building blocks (amino acids) in complement factor H. These mutations prevent cells from making this protein or lead to the production of a nonfunctional version of the protein.
A shortage (deficiency) of complement factor H can cause uncontrolled activation of the complement system. The overactive system creates debris that builds up in and damages certain structures in the kidneys. These structures, called glomeruli, are clusters of tiny blood vessels that help filter waste products from the blood. Damage to glomeruli prevents the kidneys from filtering waste products normally and can lead to end-stage renal disease (ESRD), a life-threatening failure of kidney function.
CFH gene mutations are responsible for only a small percentage of all cases of dense deposit disease. However, several common variations (polymorphisms) in the CFH gene have been associated with an increased likelihood of developing the condition. The best-studied of these polymorphisms is written as Tyr402His. Complement factor H usually has the amino acid tyrosine (Tyr) at position 402, but sometimes it has the amino acid histidine (His) instead. People with dense deposit disease are more likely than people in the general population to have histidine at this position. The version of complement factor H with histidine at position 402 is less effective at regulating the complement system on cell surfaces than the version with tyrosine at position 402, which may help explain the increased disease risk.
Several variants in and near the CFH gene have been identified in people with age-related macular degeneration, a common cause of vision loss in older adults. The Tyr402His polymorphism (described above) appears to be associated with an increased risk of the condition. People who carry one copy of this polymorphism have a 2.5-fold increased risk of developing age-related macular degeneration compared to people who do not have the polymorphism, and people who carry two copies of the polymorphism have a six-fold increased risk. However, most people with these variants never develop the disorder.
Age-related macular degeneration is characterized by the buildup of yellowish deposits called drusen underneath the light-sensitive tissue at the back of the eye (the retina). This buildup, together with other changes in the retina, leads to a progressive loss of central vision in late adulthood. Researchers suspect that changes in the CFH gene alter the production of complement factor H, although it is unclear how abnormal complement factor H is related to the buildup of drusen and progressive vision loss. Age-related macular degeneration is a complex condition that likely results from a combination of genetic and environmental factors.
More than 100 mutations in the CFH gene have been identified in people with atypical hemolytic-uremic syndrome. Mutations in this gene increase the risk of a severe form of the disorder that usually appears early in life.
Most CFH gene mutations associated with atypical hemolytic-uremic syndrome affect a region of the complement factor H protein known as the C-terminal domain. These mutations result in the production of an abnormal or nonfunctional version of the protein. A shortage of complement factor H can lead to uncontrolled activation of the complement system on the surface of cells. The overactive system attacks endothelial cells, which line small blood vessels in the kidneys. Damage to these cells often leads to kidney failure and ESRD.
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 CFH 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.
Mutations in the CFH gene have also been found to cause the kidney disorder glomerulonephritis with isolated C3 deposits (also known as glomerulonephritis C3 or GN-C3). Like atypical hemolytic-uremic syndrome and dense deposit disease, this condition is characterized by serious or life-threatening kidney malfunction. The CFH gene mutations responsible for glomerulonephritis C3 result in an abnormal or nonfunctional version of complement factor H. The defective protein allows uncontrolled activation of the complement system on the surface of cells and in the bloodstream. The overactive complement system attacks certain kidney cells, which damages the kidneys and leads to a loss of protein in the urine (proteinuria).
Polymorphisms in the CFH gene, including the Tyr402His variant, have also been associated with a buildup of drusen beneath the retina starting in early adulthood. This eye condition is known as basal laminar drusen (BLD). It is unclear how changes in complement factor H are related to the accumulation of drusen in people with BLD. A combination of genetic and environmental factors likely determines the risk of developing this complex disorder.
Cytogenetic Location: 1q32
Molecular Location on chromosome 1: base pairs 196,651,877 to 196,747,503
The CFH gene is located on the long (q) arm of chromosome 1 at position 32.
More precisely, the CFH gene is located from base pair 196,651,877 to base pair 196,747,503 on chromosome 1.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about CFH helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; amino acid ; atypical ; bacteria ; cancer ; cell ; chronic ; deficiency ; domain ; endothelial cells ; end-stage renal disease ; epithelium ; ESRD ; gene ; His ; histidine ; immune response ; innate immunity ; kidney ; pigment ; polymorphism ; population ; protein ; proteinuria ; renal ; renal disease ; retina ; stage ; susceptibility ; syndrome ; tissue ; Tyr ; tyrosine
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.