The CFHR5 gene helps control part of the immune system called complement, which protects against infection but needs to stay balanced so it does not irritate healthy tissue. This gene plays an important role in the kidneys, where it helps limit inflammation in the tiny filters that clean your blood. If the gene does not work properly, complement activity can become too strong and may lead to blood in the urine, protein in the urine, and over time reduced kidney function. Certain pathogenic variants in the CFHR5 gene cause CFHR5 related kidney disease.
What is a gene?
A gene is a stretch of DNA that carries instructions your cells use to make molecules or regulate processes in the body. Some genes provide the information needed to produce proteins, the parts of cells that do much of the work. Other genes mainly help determine when certain processes happen, where they occur, and how strongly they run. Taken together, genes affect how the body develops and works, and they can also influence how you respond to food, stress, or medications. More on this topic is available in the LearnHub.
Overview
CFHR5Gene function
What if the gene works
Your immune system uses the CFHR5 gene to help control part of the body’s defense response. Its protein helps fine tune inflammation, especially in the kidneys, so healthy tissues are less likely to be harmed.
Risk
What if the gene does not work
Changes in the CFHR5 gene can affect kidney filtering by disturbing control of the complement system, part of the immune system. Effects can range from mild, repeated blood in the urine to progressive kidney disease, sometimes leading to kidney failure.
Treatment
What does that mean for your treatment
No treatment plan is currently tailored specifically to pathogenic variants in the CFHR5 gene. Care is usually guided by the kidney problem itself, while CFHR5 related complement changes are being studied to help guide complement blocking drugs in certain kidney conditions.
Conditions associated with CFHR5
Gene function
What if the gene works
Your immune system uses the CFHR5 gene to help manage part of its routine defense system. It makes a blood protein that works with complement, a group of proteins that tags microbes and helps clear waste. Understanding how the CFHR5 gene supports the complement system makes its day to day role easier to picture.
The CFHR5 gene makes a protein that helps guide complement activity, part of your immune defense. This supports a more organized response on blood and tissue surfaces where complement proteins are already active.
Its protein attaches to C3b, a complement tag placed on microbes or material marked for cleanup. This helps CFHR5 gather at spots where immune proteins are already working.
CFHR5 can also attach to certain tissue coatings and material outside cells. This helps place complement activity at specific surfaces instead of leaving it evenly spread through the bloodstream.
What is a variant?
A genetic variant is a minor change in the DNA sequence within a gene. These changes are common and help explain normal human diversity, including differences in appearance, metabolism, or how the body responds to environmental influences. Many variants do not cause any noticeable effect and are simply part of natural genetic variation. Sometimes, however, a variant can change how a gene works more substantially and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the CFHR5 gene can alter the protein’s shape, stability, or ability to attach to complement-coated surfaces, which helps explain how CFHR5 gene variants affect protein function. Some changes reduce this effect only partly, while more disruptive variants can markedly weaken control of the complement system (part of immune defense) in the kidney. This range in functional impact may influence whether CFHR5-related kidney disease appears later and stays milder or starts earlier with more persistent findings.
How variants are linked to conditions
Pathogenic variants in the CFHR5 gene are linked to inherited kidney disease, most clearly CFHR5 nephropathy. This condition can cause repeated episodes of blood in the urine and may lead to chronic kidney disease over time, with more severe kidney problems reported more often in some men. Rare variants in the CFHR5 gene have also been associated with C3 glomerulopathy, a group of kidney conditions diagnosed by specific findings on kidney testing.
A variant is not necessarily a diagnosis
Genetic variants are a normal feature of human biology and are widely seen in the general population. Most do not have a direct effect on health and simply reflect natural human diversity. For many genes, carrying a variant associated with a condition indicates a possible link rather than a definite diagnosis, especially when several genes and environmental factors are involved. In some situations, though, a single well-characterized variant in a specific gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For CFHR5, the main risk comes from inheriting a disease-causing gene change, and many living with it have a higher chance of kidney problems over time. Men are more likely than women to develop more serious kidney disease, and infections can trigger episodes of blood in the urine.
Inheritance of CFHR5 variants
CFHR5-related disease is usually inherited in an autosomal dominant pattern. That means a parent carrying a disease-causing variant in the CFHR5 gene can pass it on to each child with a 50% chance, regardless of the child’s sex. In practical terms, how CFHR5 variants are inherited often looks like the condition running through several generations of a family. A child who does not inherit the variant usually cannot pass that same family variant on to their own children.
What does my CFHR5 result mean for my family?
A disease-causing result in the CFHR5 gene can run in families in a dominant way, so close relatives such as parents, brothers, sisters, and children may also carry the same change. For many families, this means some relatives may have blood in the urine, protein in the urine, or a higher chance of kidney disease, even if they feel well. Each child of someone with the result has a 50% chance of inheriting it.
Genetic information
Genetic testing
How you find out about variants
CFHR5 genetic testing looks for variants in the CFHR5 gene using DNA from a blood sample or cheek swab. A lab reads the gene’s sequence and compares it with the usual pattern to identify changes that may help explain inherited kidney findings or a family history of blood in the urine.
When should I consider getting a genetic test?
Consider CFHR5 testing if blood in the urine, protein in the urine, or kidney disease runs in your family, especially if several relatives have had kidney failure. Testing can help show whether a change in CFHR5 is the cause and whether other family members may also carry it.
A genetic result is only one part of your health story
A genetic finding can provide useful insight, but how much it explains varies with the condition and the specific type of variant. Factors such as lifestyle, environment, age, and medical history also shape how the body functions over time. For some conditions, especially those influenced by many genes, genetic information offers context rather than certainty and makes the most sense when viewed alongside other parts of care. In other situations, a genetic result can give a definite answer. In areas such as medication response, genetic results can also help put individual experiences in context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body responds to medicines. Some people break down a drug more slowly or more quickly, while others are more or less sensitive to its effects. This helps explain why the same treatment works well for one person but causes side effects or less benefit in another. These differences are common and are one reason medication response can vary from person to person.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can shape a person’s response to medications. By studying links between genes and drugs, it helps explain why the same treatment may work differently from one person to another. For many medicines, genes can affect how strongly a drug works or how the body handles it. This information can support more personalized and better informed treatment choices. You can read more about this topic in the LearnHub.
Drugs influenced by the CFHR5 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medication choice or dose, so questions about medicines, side effects, or your overall health are best discussed with your doctor.
History
CFHR5 entered the medical literature through families in Cyprus who shared a distinctive pattern of blood in the urine and gradual kidney problems across generations. In recent decades, awareness of this gene’s role has grown as researchers linked this inherited kidney condition to a region on chromosome 1. From these first observations, research expanded steadily, and scientists identified a disease causing variant in the CFHR5 gene in Cypriot families around 2010. This helped establish what is now commonly called CFHR5 nephropathy, a form of inherited kidney disease. Since then, additional reports from other families have shown that changes in the CFHR5 gene can be found beyond Cyprus, while the Cypriot cases remain the best known historical starting point.