The LRBA gene helps immune cells control how strongly they react and supports the recycling of CTLA-4, a protein that puts the brakes on immune activity. If the LRBA gene does not work properly, the immune system may become overactive in some places and too weak in others. This gene plays an important role in keeping immune responses balanced. People with harmful variants can have repeated infections, low antibody levels, chronic diarrhea, or autoimmune problems such as low blood counts.
What is a gene?
A gene is a section of DNA that carries instructions your cells use to make molecules or regulate processes in the body. Some genes provide the instructions for producing proteins, which are the active parts of cells. Others are mainly involved in controlling when certain processes happen, where they happen, and how active they are. Taken together, genes affect how the body grows and works, and they can also influence how you respond to food, stress, or medicines. To go into this topic in greater depth, you can read more in the LearnHub.
Overview
LRBAGene function
What if the gene works
The LRBA gene helps immune cells recycle and protect key proteins, including CTLA-4. This supports balanced immune responses and helps the body fight infections without attacking its own tissues.
Risk
What if the gene does not work
Changes in the LRBA gene can disrupt immune balance, often causing infections and autoimmune problems such as bowel inflammation, low blood counts, or diabetes. Milder and more severe variants can influence when symptoms start and how many systems are involved.
Treatment
What does that mean for your treatment
With pathogenic variants in the LRBA gene, abatacept is a well-established targeted treatment because it can restore a key immune calming signal and help control immune overactivity. Immunoglobulin replacement may also be used, and stem cell transplant is considered for severe or treatment-resistant cases.
Conditions associated with LRBA
Gene function
What if the gene works
In immune cells, the LRBA gene helps move and recycle important proteins inside the cell. This steady traffic keeps key surface signals available when they are needed. Understanding what the LRBA gene does in immune cells helps show how the body keeps defense responses balanced.
The LRBA gene helps sort cell cargo into small transport sacs so proteins can be sent to the right place. This supports the routine flow of materials between different parts of the cell and the cell surface.
Its protein helps cells bring certain surface proteins back inside and return them for reuse instead of breaking them down. This recycling system helps important signals stay available at the right time.
In key immune cells, its protein helps preserve CTLA-4, a protein that acts like a brake on immune responses. This supports controlled signaling so the body can respond without overreacting.
What is a variant?
A genetic variant is a small change in the DNA sequence within a gene. These changes are common and help shape normal human diversity, such as differences in appearance, metabolism, or how the body responds to environmental influences. Many variants do not have any noticeable effect and simply represent natural genetic variation. In some situations, though, 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 LRBA gene often lower the amount of LRBA protein or make it unstable, which can disrupt how immune cells recycle CTLA-4, an important immune brake. More disruptive variants may leave little or no working protein, while milder variants can preserve some activity. This range in how variants in the LRBA gene affect immune cell function often helps explain why some people develop earlier or broader immune problems than others.
How variants are linked to conditions
LRBA gene variants can cause LRBA deficiency, a rare inherited immune condition. People with this diagnosis often have repeated infections, low antibody levels, autoimmune problems such as low blood cell counts, and ongoing gut inflammation that may cause chronic diarrhea. Some also develop enlarged lymph nodes, liver, or spleen, and children may have poor growth.
A variant is not necessarily a diagnosis
Genetic variants are a usual feature of human biology and are widespread in the general population. Most do not have a direct effect on health and instead reflect normal human diversity. For many genes, having a variant associated with a condition suggests a possible link rather than a confirmed 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 LRBA, risk is mainly shaped by whether someone has disease-causing changes in both copies of the gene, so lifestyle factors are not known to meaningfully change the chance of having the condition. The main practical steps are early recognition, monitoring for infections and immune problems, and medical care to help prevent complications.
Inheritance of LRBA variants
For families discussing the LRBA inheritance pattern, disease causing variants in the LRBA gene are inherited in an autosomal recessive way. This means a child usually inherits one altered copy from each parent. Parents who carry one LRBA variant are typically unaffected carriers. When both parents are carriers, each pregnancy has a 25% chance of a child with the condition, a 50% chance of a child who is a carrier, and a 25% chance of a child with two working copies.
What does my LRBA result mean for my family?
For families affected by LRBA, this result usually means close relatives could also carry the same gene change. Brothers and sisters may also be affected or may be healthy carriers, and parents are often carriers without having symptoms themselves. Other relatives, such as future children or extended family members, may also want to learn whether this runs in the family.
Genetic information
Genetic testing
How you find out about variants
Genetic testing for LRBA variants usually uses a blood or saliva sample, which a lab analyzes by reading the LRBA gene for changes in its DNA code. Testing may look at the LRBA gene alone or include it in a larger immune system gene panel, and the results can show whether a variant is present, absent, or of uncertain meaning.
When should I consider getting a genetic test?
Genetic testing for LRBA may be considered when someone has repeated serious infections, long-lasting diarrhea, poor growth, or immune problems such as the body attacking its own blood cells, especially from childhood. It can also help when similar problems run in the family.
A genetic result is only one part of your health story
A genetic result can provide valuable insight, but how much it explains varies based on the condition and the type of variant involved. Many factors, including lifestyle, environment, age, and medical history, influence how the body functions over time. In some conditions, especially those shaped by many genes, genetic information provides context rather than certainty and is best considered alongside other parts of care. In other situations, a genetic result can offer a clear answer. In areas like medication response, genetic results can also help put individual experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Small differences in genes can change how the body breaks down a drug, moves it through the bloodstream, or responds to it where it acts. This helps explain why the same medication works well for one person, has less effect in another, or causes more side effects in someone else. These differences are common and are one of several factors, along with age, liver and kidney function, and other medicines, that shape treatment response.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can shape a person’s response to medications. It studies connections between genes and drugs to help explain why the same treatment may affect people differently. For many medicines, genes can 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. More detailed information on this topic is available in the LearnHub.
Drugs influenced by the LRBA gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in predicting medication response, so concerns about side effects, new symptoms, or whether a medicine is helping are best discussed with your doctor.
History
Researchers identified the LRBA gene in the late 1990s while studying a large protein involved in immune cell biology. At first, it was mainly of interest in laboratory research rather than everyday clinical care. Over time, descriptions became more precise. A major shift came in 2012, when biallelic pathogenic variants in the LRBA gene were linked to a recognizable inherited immune condition in children and adults. That discovery helped connect years of unexplained autoimmune symptoms, recurrent infections, and low antibody levels to a single genetic cause in some families. In the years that followed, wider use of genetic sequencing made LRBA-related disease easier to identify and shaped more targeted approaches to diagnosis and care.