The SERPINA1 gene provides instructions for alpha-1 antitrypsin, a protein made mainly in the liver that helps protect the lungs from damage during inflammation. If the gene does not work well, you may make too little of this protein, or an altered form can build up in the liver. This gene plays an important role in keeping breathing tissues and liver cells healthier over time. Certain variants are linked to alpha-1 antitrypsin deficiency, which can raise the chance of emphysema, chronic cough, or liver disease.
What is a gene?
Genes are stretches of DNA that carry instructions your cells use to make molecules or regulate processes in the body. Some genes contain the directions for producing proteins, the parts of cells that do the work. Other genes mainly control when certain processes happen, where they take place, and how strongly they run. Together, genes affect how the body develops and functions, and they can influence how you respond to food, stress, or medications. For a deeper look at this topic, you can learn more in the LearnHub.
Overview
SERPINA1Gene function
What if the gene works
The SERPINA1 gene makes alpha-1 antitrypsin, a protein mainly produced in the liver. It helps protect the lungs from enzyme damage during inflammation.
Risk
What if the gene does not work
Variants in the SERPINA1 gene can reduce alpha-1 antitrypsin, which may raise the chance of early emphysema and liver disease. Milder variants may cause little or no illness, while more severe variants can lead to earlier, broader effects.
Treatment
What does that mean for your treatment
Pathogenic variants in the SERPINA1 gene can make some adults eligible for intravenous alpha-1 antitrypsin augmentation therapy when lung disease is present and deficiency is severe. This treatment raises alpha-1 antitrypsin levels and is not used for SERPINA1-related liver disease.
Conditions associated with SERPINA1
Gene function
What if the gene works
In everyday life, your tissues face normal wear from breathing, movement, and minor inflammation. The SERPINA1 gene helps keep that wear under control by making alpha-1 antitrypsin, a protective protein that travels in the blood. It is especially important for shielding delicate lung tissue and helping your body maintain a healthy balance between tissue breakdown and repair.
Alpha-1 antitrypsin from the SERPINA1 gene helps protect the tiny air sacs in your lungs during normal breathing and inflammation. It calms enzyme activity so lung tissue is not worn down faster than it can be maintained.
One of the main jobs of this protein is to block elastase, an enzyme that can break down elastic tissue. This steady control helps the body use protein cutting tools where they are needed without letting them spread too far.
The SERPINA1 gene supports the balance between normal tissue breakdown and repair, especially in the lungs. This is part of how your lungs are protected during inflammation and everyday exposure to dust, smoke, and infections.
Most alpha-1 antitrypsin is made in the liver and then released into the bloodstream. This lets the protein reach tissues throughout the body, with an especially important protective role in the lungs.
What is a variant?
A genetic variant is a minor change in the DNA sequence within a gene. These changes are common and help shape normal differences among people, such as appearance, metabolism, or how the body responds to environmental influences. Many have no noticeable effect at all and simply represent natural genetic variation. Sometimes, though, a variant can more clearly change how a gene works and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the SERPINA1 gene can lower the amount of alpha-1 antitrypsin released into the blood or change its shape so the protein gets trapped inside liver cells. Across SERPINA1 gene variants, milder changes may leave some protein activity, while more severe variants can sharply reduce levels or cause more buildup. This range helps explain why alpha-1 antitrypsin deficiency can vary, including how early signs appear and whether the liver, lungs, or both are involved.
How variants are linked to conditions
Variants in the SERPINA1 gene cause alpha-1 antitrypsin deficiency, a condition linked to emphysema, chronic obstructive pulmonary disease, and liver disease. Inherited changes in both copies of the gene are the main cause, while carrying one changed copy may still matter in some people. In practice, the SERPINA1 gene and alpha-1 antitrypsin deficiency are most often discussed when doctors evaluate unexplained lung disease or abnormal liver tests.
A variant is not necessarily a diagnosis
Genetic variants are common across the general population and are a normal part of human biology. 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 suggests a possible link rather than a definite diagnosis, especially when several genes and environmental factors also play a role. In some situations, though, a single well-characterized variant in a particular gene can be enough to confirm a diagnosis.
Are there things that can increase or change my risk?
With SERPINA1, the inherited gene change is the main reason risk is higher, but smoking greatly increases the chance of lung damage and often makes symptoms start earlier. Dust, fumes, and air pollution can also worsen lung problems. Heavy alcohol use and liver infections can add to the risk of liver disease.
Inheritance of SERPINA1 variants
Variants in the SERPINA1 gene are usually inherited in an autosomal codominant pattern, which means you inherit one copy from each parent and both copies can affect your alpha-1 antitrypsin level. Understanding how variants of the SERPINA1 gene are inherited helps explain why a child may receive a risk-linked copy from either parent, and why brothers and sisters can be affected differently. If both parents carry a variant, their children can inherit two changed copies, one changed copy, or neither. Because SERPINA1 is on a nonsex chromosome, this inheritance pattern is the same for males and females.
What does my SERPINA1 result mean for my family?
Changes in the SERPINA1 gene can run in families. Close relatives may also carry the same change, and some may have alpha-1 antitrypsin deficiency or be carriers without knowing it. Brothers, sisters, children, and parents can have a shared family risk, so the result may be relevant beyond just one person. The exact meaning for relatives depends on the specific SERPINA1 result found.
Genetic information
Genetic testing
How you find out about variants
Genetic testing for variants in the SERPINA1 gene uses a blood or saliva sample to look for DNA changes that can be passed through families. Some labs check for the most common SERPINA1 variants first, while others read the full gene, which can give a more complete result.
When should I consider getting a genetic test?
Testing for changes in the SERPINA1 gene can be worth considering if you or a close relative has alpha-1 antitrypsin deficiency, early emphysema or COPD, especially without much smoking, or ongoing unexplained liver disease. It can also help clarify risk for close family members when one relative is known to carry a SERPINA1 change.
A genetic result is only one part of your health story
A genetic test result can provide useful insight, but how much it reveals depends on the condition and the kind of variant involved. Over time, many factors, including lifestyle, environment, age, and medical history, shape how the body works. In some conditions, especially those influenced by many genes, genetic information offers context rather than certainty and is best understood together with other parts of care. In other situations, a genetic result can give a clear answer. In areas like medication response, it can also help put individual experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body responds to medicines. This helps explain why the same treatment works well for one person, seems weaker for another, or causes more side effects in someone else. Differences in how the body breaks down, moves, or responds to a drug are common, and they can influence both benefit and sensitivity.
What is Pharmacogenetics?
Pharmacogenetics examines how differences in genes affect the way people respond to medicines. It studies patterns between genes and drugs to understand why the same treatment can 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 and individualized treatment decisions. More on this topic is available in the LearnHub.
Drugs influenced by the SERPINA1 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in predicting how medicines will work or which side effects may happen. Questions about medicines, treatment changes, or health concerns linked to breathing or liver symptoms are best discussed with your doctor.
History
In 1963, Swedish researchers Carl-Bertil Laurell and Sten Eriksson reported that some people with early emphysema had very low levels of alpha-1 antitrypsin in their blood, which marked the first clear description of the condition tied to the SERPINA1 gene. Initially understood only through visible traits, later recognized as tied to a specific gene, this finding became an important milestone in medical genetics. Over the following years, doctors also linked inherited changes in the SERPINA1 gene to liver disease in children and adults. Researchers then mapped the protein types, including the well-known PI*Z variant, which helped families and clinicians understand why the condition could run in families. These historical steps shaped today’s understanding of alpha-1 antitrypsin deficiency and inherited risk.