Your immune system uses the IFNGR2 gene to respond to interferon gamma, an alarm signal that helps cells fight germs living inside them. This gene plays an important role in controlling infections caused by mycobacteria, including the bacteria used in the BCG vaccine. If the IFNGR2 gene does not work, the body may struggle to contain these germs, and some people develop unusual or repeated infections, often starting in childhood.
What is a gene?
Genes are sections of DNA that provide your cells with instructions for making molecules or directing processes in the body. Some genes hold the information needed to produce proteins, the working parts of cells. Others mainly help regulate when certain processes take place, where they happen, and how strongly they run. Taken together, genes affect how the body develops and works, and they can influence how you respond to food, stress, or medications. To explore this topic in more detail, you can learn more in the LearnHub.
Overview
IFNGR2Gene function
What if the gene works
The IFNGR2 gene helps cells respond to interferon gamma, an immune signal. This supports immune defenses, especially against germs that live inside cells.
Risk
What if the gene does not work
Variants in the IFNGR2 gene can weaken the body’s interferon gamma response, raising the chance of unusual or severe mycobacterial infections, including after BCG vaccination. Milder or more severe variants can affect when problems start and how severe they are.
Treatment
What does that mean for your treatment
Pathogenic variants in the IFNGR2 gene can make interferon gamma treatment ineffective, especially in complete IFNGR2 deficiency, because the signal cannot be passed into immune cells. Management usually relies on antimycobacterial treatment, and hematopoietic stem cell transplantation is the main disease specific option for severe complete deficiency.
Conditions associated with IFNGR2
Gene function
What if the gene works
Your immune system uses the IFNGR2 gene to respond to interferon gamma, a key chemical message between immune cells. This is part of normal interferon gamma receptor function, which helps cells react when the immune system raises an alarm. These signals help cells adjust their defense activity in a controlled way.
The IFNGR2 gene provides one part of the cell surface receiver for interferon gamma. It works with the IFNGR1 gene so cells can detect this immune message clearly.
After the signal is received, the IFNGR2 gene helps carry it from the cell surface into the cell. This switches on internal pathways that tell the cell which defense genes to use.
Signals through the IFNGR2 gene help immune cells strengthen their response to germs, especially those living inside cells. They also support communication between immune cells so the response stays organized.
What is a variant?
A genetic variant is a minor change in the DNA sequence within a gene. These changes are common and help account for normal human diversity, including differences in appearance, metabolism, or the way the body responds to environmental influences. Many variants do not cause any noticeable effect and are simply part of natural genetic variation. In some situations, however, 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
Variants in the IFNGR2 gene can change the receptor so too little is made, it becomes unstable, it does not reach the cell surface, or it cannot pass along the interferon gamma signal inside immune cells. This is how IFNGR2 gene variants affect the receptor at a cellular level. Milder variants may leave some signaling, while more severe variants can block it almost completely, often leading to earlier or more pronounced susceptibility to mycobacterial infection.
How variants are linked to conditions
Pathogenic variants in the IFNGR2 gene cause a rare inherited immune condition called Mendelian susceptibility to mycobacterial disease. This means some people are more likely to develop severe or repeated illness from certain mycobacterial infections, including the BCG vaccine strain and environmental mycobacteria found in soil and water. Some may also have repeated Salmonella infections.
A variant is not necessarily a diagnosis
Variants in our genes are a usual part of human biology and are widespread in the general population. Most do not have a direct effect on health and instead reflect normal human variation. 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 also play a role. 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?
With harmful changes in IFNGR2, the main risk comes from the gene change itself rather than lifestyle. Risk of serious infection can be higher after exposure to certain mycobacteria, including the BCG vaccine used against tuberculosis in some countries, and sometimes after Salmonella infection. Early recognition and close medical follow-up matter most.
Inheritance of IFNGR2 variants
Variants in the IFNGR2 gene are inherited in an autosomal recessive pattern. In practical terms, this means a child usually inherits one changed copy from each parent, and the parents are often healthy carriers. When both parents carry an IFNGR2 gene variant, each pregnancy has a 25% chance of resulting in a child with the condition, a 50% chance of a child who is also a carrier, and a 25% chance of a child who inherits neither variant. This is the established answer to how variants of the IFNGR2 gene are inherited for IFNGR2-related disease.
What does my IFNGR2 result mean for my family?
For IFNGR2, family impact is usually discussed as a recessive inherited condition. This often means parents may be healthy carriers, brothers and sisters could also be affected or be carriers, and other close relatives may also carry the same change. What this means for relatives depends on the exact result found in the family.
Genetic information
Genetic testing
How you find out about variants
IFNGR2 genetic testing usually starts with a blood or saliva sample, which a lab analyzes by reading the DNA code for the IFNGR2 gene. This can find variants in IFNGR2 and may help confirm whether an inherited cause is present when doctors are assessing unusual or repeated mycobacterial infections.
When should I consider getting a genetic test?
Consider genetic testing for the IFNGR2 gene if someone has severe or repeated infections caused by TB-related bacteria, especially after the BCG vaccine, or if these infections run in the family. Testing can help explain why the immune system is not handling certain germs normally and may confirm an inherited condition.
A genetic result is only one part of your health story
A genetic result can provide valuable insight, but how much it reveals depends on the condition and the kind of variant involved. Many factors, including lifestyle, environment, age, and medical history, influence how the body works over time. For some conditions, especially those shaped by many genes, genetic information provides context rather than certainty and is best understood alongside other parts of care. In other situations, a genetic result may offer a clear answer. In areas such as medication response, genetic results can also help put individual experiences in perspective.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Two people can take the same treatment and have different results because their bodies may absorb, break down, or respond to a drug in different ways. These inherited differences are common and can influence how well a medicine works or how sensitive someone is to side effects. Medication response also depends on other factors, including age, liver and kidney function, and other medicines a person takes.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences shape a person’s response to medications. It looks at gene-drug patterns to help explain why the same treatment may work differently from one person to another. For many medicines, genes influence how strongly a drug works or how the body handles it. This information can support more informed, more individualized treatment decisions. To explore this topic in greater detail, you can learn more in the LearnHub.
Drugs influenced by the IFNGR2 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 if you have questions about side effects, a new prescription, or how well a treatment is working, it is best to talk with your doctor.
History
IFNGR2 entered the scientific literature in the 1990s, when researchers were working to map the parts of the receptor used by interferon gamma, an important immune signaling protein. Initially understood only through cell studies, later recognized as tied to a specific gene, IFNGR2 helped clarify why some people had unusual vulnerability to certain infections despite otherwise typical health. From these first observations, research expanded steadily. Reports of families with inherited susceptibility to mycobacterial infection helped confirm the gene’s medical importance and shaped a broader understanding of rare immune conditions. Over time, descriptions became more precise, linking different IFNGR2 variants with different degrees of immune impairment. These historical steps shaped today’s understanding of IFNGR2 in clinical genetics and immunology.