The TM6SF2 gene helps the liver package and release fats into the bloodstream. If it does not work well, fat can build up in the liver, which may raise the chance of fatty liver disease, while blood levels of triglycerides and LDL cholesterol may be lower. Some people first learn about this gene during testing for unexplained high liver fat or abnormal liver enzymes. Most TM6SF2 variants have little effect, but a few can meaningfully change liver health risk.
What is a gene?
Genes are sections of DNA that carry instructions cells use to make molecules or regulate activities in the body. Some genes provide the directions for producing proteins, which do much of the cell's work. Others are used mainly to manage 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 influence how you respond to food, stress, and medicines. More detail is available in the LearnHub.
Overview
TM6SF2Gene function
What if the gene works
The TM6SF2 gene helps liver cells package and release fats into the bloodstream. This supports normal handling of triglycerides and helps limit fat buildup in the liver.
Risk
What if the gene does not work
Variants in the TM6SF2 gene can change how the liver handles fat, raising the chance of fatty liver, inflammation, and scarring. Effects range from milder to more severe variants, which may influence when changes appear and how marked they are.
Treatment
What does that mean for your treatment
No TM6SF2-specific treatment or drug choice is currently established in clinical guidelines for people with a pathogenic or loss-of-function variant in the TM6SF2 gene. TM6SF2 variants are being studied mainly as biomarkers of fatty liver severity and liver-related risk, rather than as a guide to a specific medicine.
Gene function
What if the gene works
The TM6SF2 gene helps your body handle fats as part of everyday metabolism. It is most active in the liver and small intestine, where cells package fats into particles that can move through the blood. This supports normal energy use and fat transport. It also explains what the TM6SF2 gene does in the liver during routine fat processing.
In liver and intestine cells, the TM6SF2 gene helps load fats into particles that can travel through the bloodstream. This gives cells a controlled way to move fat out for use or storage elsewhere.
In the liver, the TM6SF2 gene supports the release of VLDL, which are fat carrying particles made by the liver. These particles deliver triglycerides, a common form of fat, to other tissues.
In the small intestine, the TM6SF2 gene helps package fats absorbed from food into transport particles. This supports the normal movement of meal related fats from the gut into circulation.
What is a variant?
A genetic variant is a minor difference in the DNA sequence within a gene. These differences are common and help shape normal human diversity, including variation in appearance, metabolism, and the way the body responds to environmental factors. Many do not cause any noticeable effect and are simply part of natural genetic variation. Sometimes, though, a variant changes how a gene works more significantly and can contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the TM6SF2 gene can make the protein less stable or reduce how much of it reaches liver cells, which changes how TM6SF2 gene variants affect liver fat handling. Many variants lead to partial loss of function, while more disruptive variants can cause a larger drop in activity. Stronger loss of function is often linked to more fat staying inside liver cells and, in some people, earlier or more marked fatty liver changes.
How variants are linked to conditions
Variants in the TM6SF2 gene are most strongly associated with metabolic dysfunction associated steatotic liver disease, a common fatty liver condition, and some variants are linked to a higher chance of steatohepatitis and liver scarring. This TM6SF2 gene fatty liver risk does not mean liver disease is certain, but studies consistently connect certain changes, especially p.Glu167Lys, with more liver fat. The same variant is also often associated with lower blood triglyceride and LDL cholesterol levels.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are common throughout the general population. Most have no direct impact 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 more than one gene 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 TM6SF2, risk is shaped by more than the gene alone. A risk-related change in TM6SF2 can raise the chance of fat building up in the liver, especially with excess body weight, type 2 diabetes, high blood fats, or regular alcohol use. These factors can also affect how severe liver problems become over time.
Inheritance of TM6SF2 variants
For families asking how TM6SF2 gene variants are inherited, there is not yet a broadly confirmed Mendelian pattern tied to one specific TM6SF2 related condition. TM6SF2 changes are most often discussed as inherited genetic factors that may influence traits such as liver fat and blood lipid levels, rather than as a single-gene condition passed down in a clearly dominant or recessive way. The TM6SF2 gene is located on chromosome 19, which is an autosome, so you inherit one copy from each parent. This means either parent can pass a TM6SF2 variant to a child.
What does my TM6SF2 result mean for my family?
There is not yet a broadly confirmed inheritance pattern tied to a specific single-gene condition for TM6SF2. Changes in TM6SF2 are better understood as influencing the chance of fatty liver and related health issues rather than causing a clear-cut inherited condition on their own, so what this means for relatives depends on the full family and health picture.
Genetic information
Genetic testing
How you find out about variants
TM6SF2 genetic testing uses a saliva or blood sample to look for specific DNA variants in the TM6SF2 gene. If you are trying to understand how TM6SF2 genetic testing works, the lab reads this part of your DNA and reports whether a known variant is present.
When should I consider getting a genetic test?
There is not yet a broadly established TM6SF2-specific reason to get genetic testing in routine care. Changes in this gene can affect the chance of fatty liver disease and blood fat levels, but testing is usually considered only as part of a broader review of your personal and family history with a doctor or genetic counselor.
A genetic result is only one part of your health story
A genetic result can provide useful insight, but how much it reveals depends on the condition and the kind of variant involved. Lifestyle, environment, age, and medical history are among the many factors that influence how the body functions over time. In some conditions, especially those shaped by many genes, genetic information offers context rather than certainty and is most helpful when considered with other parts of care. In other situations, a genetic result can give a clear answer. In areas like 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 people respond to medicines. Two people taking the same treatment may process it differently because inherited differences can change how the body absorbs, breaks down, or responds to a drug. This is common and can influence how well a medicine works or how sensitive someone is to side effects.
What is Pharmacogenetics?
Pharmacogenetics examines how differences in genes can affect a person’s response to medications. It studies the relationship between genes and drugs to help explain why the same treatment may work differently from one person to another. For many medicines, genes can influence how strongly a drug works or how the body processes it. This information can support more informed, more individualized treatment decisions. To explore this subject in greater depth, you can learn more in the LearnHub.
Drugs influenced by the TM6SF2 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medicine choices, so questions about side effects, changing doses, or whether a treatment is working are best discussed with your doctor.
History
TM6SF2 entered medical genetics relatively recently, compared with genes known for decades. In 2014, researchers began exploring how this gene works after studies linked variants in the TM6SF2 gene with differences in liver fat and blood lipid levels. From these first observations, research expanded steadily, especially in studies of fatty liver disease and metabolic health. Scientific interest grew because TM6SF2 helped explain why some people can have more fat stored in the liver while showing different cholesterol patterns in blood tests. Although the TM6SF2 gene has not become a major public awareness gene, it is now recognized as an important part of research on inherited influences on liver and heart related health.