The APOL1 gene helps make a protein in the blood that helps protect against certain parasites. When specific variants change how this gene works, some people have a higher chance of kidney damage and chronic kidney disease, especially those with recent African ancestry. Many people with these variants never develop kidney problems. Understanding this gene can help make sense of kidney risk in some families.
What is a gene?
Genes are stretches of DNA that give your cells instructions they can use to make molecules or regulate activities in the body. Some genes carry the information needed to produce proteins, which do much of the work inside cells. Others mainly help control when certain processes happen, where they take place, and how strongly they operate. Taken together, genes influence how the body develops and functions, and they can shape how you respond to food, stress, or medications. More on this topic is available in the LearnHub.
Overview
APOL1Gene function
What if the gene works
The APOL1 gene helps make a blood protein that is part of the body’s early immune defense. This protein can help protect against certain parasites, including some that cause African sleeping sickness.
Risk
What if the gene does not work
Some variants in the APOL1 gene can raise kidney disease risk, especially with two risk copies. Effects vary: milder changes may do little, while stronger risk variants can be linked to earlier or more severe kidney problems.
Treatment
What does that mean for your treatment
No treatment or drug choice is currently established specifically for pathogenic variants in the APOL1 gene in routine care. The APOL1 gene is an active drug target in kidney disease research, and medicines such as inaxaplin are being studied for APOL1 related kidney disease.
Conditions associated with APOL1
Gene function
What if the gene works
If you carry the APOL1 gene, its main job is tied to your body’s early defense system in the bloodstream. It helps make a protein that travels in blood and can damage certain parasites. Understanding how the APOL1 gene helps protect the body from certain parasites also shows why it matters for routine immune function.
The APOL1 gene helps make a protein that is part of your blood’s first line of defense against certain trypanosomes, a type of parasite. Once inside the parasite, the protein makes openings in internal membranes, which helps break the parasite apart.
The protein made from the APOL1 gene can attach to fats and join HDL, a blood particle that carries fat and protein. This helps it travel through the bloodstream in a stable form and support routine immune defense.
What is a variant?
A genetic variant is a small difference in the DNA sequence of a gene. These differences are common and help account for normal human diversity, such as differences in appearance, metabolism, or how the body responds to environmental influences. Many variants do not cause any noticeable effect and simply represent natural genetic variation. In some cases, though, a variant can change how a gene functions more substantially and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Common variants in the APOL1 gene, especially APOL1 G1 and APOL1 G2, alter the tail end of the protein and its interactions with cell membranes. This helps explain how APOL1 variants affect protein function: the altered protein may form abnormal pores and switch on cell stress pathways, especially in kidney cells. One risk variant usually changes cell behavior less, while two risk variants often cause a stronger cell stress effect and can track with earlier or more severe kidney disease.
How variants are linked to conditions
Variants in the APOL1 gene, especially APOL1 G1 and APOL1 G2, are most strongly linked to APOL1 gene kidney disease risk. Inheriting two risk variants is associated with a higher chance of chronic kidney disease and focal segmental glomerulosclerosis. It is also linked to HIV associated kidney disease and faster progression to kidney failure, especially in people with recent African ancestry. Many people with two risk variants never develop kidney disease.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are widespread in the general population. Most do not have a direct effect on health and instead are part of normal human variation. For many genes, having a variant associated with a condition indicates a possible link rather than a certain diagnosis, especially when several genes and environmental factors are involved. In other cases, 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 APOL1, risk is highest in people who inherit two higher-risk gene changes, but not everyone with them develops kidney disease. Other factors can also matter, especially HIV infection, ongoing high blood pressure, diabetes, and other causes of kidney strain. Keeping these conditions well controlled can help lower the chance of kidney damage and slow problems from getting worse.
Inheritance of APOL1 variants
There is not a single broadly confirmed Mendelian pattern for all APOL1-related health effects, because APOL1 kidney risk is usually discussed as a risk genotype rather than a guaranteed inherited condition. In practice, how APOL1 variants are inherited often comes down to whether a person receives one risk variant or two: the higher-risk pattern is usually seen when two APOL1 risk variants are inherited, one from each parent. The APOL1 gene is located on chromosome 22, which is an autosome, so copies of this gene are inherited from both parents regardless of sex.
What does my APOL1 result mean for my family?
There is not a broadly confirmed single-gene inheritance pattern tied to one specific APOL1 condition in the way seen with classic inherited conditions. APOL1 results are usually about a higher or lower chance of certain kidney problems, and what they mean for relatives can depend on the exact result and family history, so a doctor or genetic counselor can help explain this for your family.
Genetic information
Genetic testing
How you find out about variants
APOL1 genetic testing checks a blood or saliva sample for common changes in the APOL1 gene, especially the G1 and G2 variants. A lab reads the DNA and reports whether you carry zero, one, or two risk variants, which can help clarify inherited kidney risk.
When should I consider getting a genetic test?
APOL1 testing may be worth discussing if you have kidney disease without a clear cause, a strong family history of kidney failure, or you are being evaluated for kidney donation or transplant, especially if your family background includes recent African ancestry. APOL1 changes raise risk but do not guarantee kidney disease.
A genetic result is only one part of your health story
Genetic findings can provide valuable insight, but how much they reveal depends on the condition and the type of variant involved. Many other factors, including 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 provides context rather than certainty and is most useful when considered alongside other parts of care. In other situations, a genetic result may offer a clear answer. In areas like medication response, genetic results can also help put a person’s individual experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Two people taking the same treatment may absorb it, break it down, or move it through the body in different ways because their genes influence how certain body systems handle drugs. These differences are common and can shape how well a medicine works or how sensitive someone is to side effects. Genetic results are one part of the picture, along with age, kidney and liver function, other medicines, and overall health.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can affect a person’s response to medications. By looking at relationships between genes and drugs, it helps explain why the same treatment may work differently from one person to another. For many medicines, genes influence both how strongly a drug works and how the body processes it. This information can support treatment decisions that are more informed and more individualized. You can read more about this topic in the LearnHub.
Drugs influenced by the APOL1 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medication choices, so questions about medicines, side effects, or your overall health are best discussed with your doctor.
History
Across cultures and time periods, inherited patterns were noted in families affected by kidney disease, long before the APOL1 gene was identified. In recent decades, awareness of this gene’s role has grown as researchers studied why some kidney conditions were more common in people with recent African ancestry. A major shift came in 2010, when studies linked specific APOL1 variants to a much higher risk of certain kidney diseases. This finding changed earlier ideas that had focused mainly on high blood pressure as the explanation. Scientists then connected the story to human history, showing that these variants became more common in parts of Africa because they helped protect against a form of sleeping sickness. From these first observations, research expanded steadily.