TM6SF2 rs58542926: What Your Genotype Means for Liver Health
The rs58542926 variant in the TM6SF2 gene is a well-studied genetic marker associated with an increased risk of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis. Interestingly, while it poses risks to liver health, the same variant is often associated with lower levels of circulating serum lipids, suggesting a complex role in human metabolism.
What each genotype means
Typical liver lipid profile
This is the most common genotype and is considered the baseline for TM6SF2 function. Individuals with this genotype do not carry the specific genetic risk factor associated with increased hepatic fat accumulation linked to this variant. Please note that liver health is influenced by many factors, including diet, lifestyle, and other genetic markers.
This is the most prevalent genotype across all major global populations.
Increased liver fat risk
Carrying one copy of the T allele is associated with a higher risk of non-alcoholic fatty liver disease (NAFLD) and potential progression to hepatic fibrosis. Paradoxically, this variant is often associated with lower levels of circulating serum lipids, which may suggest a reduced cardiovascular risk profile despite the increased liver fat. You should discuss your liver health and metabolic markers with your healthcare provider.
This genotype is found in a significant portion of the population, particularly in individuals of European ancestry, though it is less common in other groups.
Elevated liver fat risk
Carrying two copies of the T allele is associated with a higher predisposition to hepatic steatosis and advanced fibrosis compared to those without the variant. While this genotype is linked to increased liver fat, it is also associated with lower circulating lipid levels, which may influence cardiovascular risk assessments. Because this genotype is relatively rare, you should consult with a clinician to interpret these findings in the context of your overall metabolic health.
This genotype is uncommon in most populations, occurring at a lower frequency than the CT or CC genotypes.
Understanding the rs58542926 Variant
The rs58542926 variant is a single nucleotide polymorphism (SNP) located within the TM6SF2 gene. In genetic terms, this variant is a nonsynonymous mutation, meaning it causes a change in the amino acid sequence of the protein produced by the gene. Specifically, it results in a glutamate-to-lysine substitution at position 167 (often referred to as E167K). This change can alter the function of the TM6SF2 protein, which is primarily expressed in the liver and small intestine. Because this protein is involved in the regulation of lipid metabolism, changes to its structure can have downstream effects on how the body processes fats. Researchers track this specific location in the genome to understand how these structural changes contribute to metabolic differences between individuals.
The Role of the TM6SF2 Gene
The TM6SF2 gene encodes the Transmembrane 6 Superfamily Member 2 protein. Current research indicates that this protein plays a critical role in the secretion of very-low-density lipoproteins (VLDL) from the liver. When the TM6SF2 protein functions normally, it helps export lipids out of liver cells. However, the T allele of the rs58542926 variant is associated with a loss-of-function effect, which can impair this export process. When lipid export is hindered, fats can accumulate within the liver, leading to hepatic steatosis, or fatty liver. This mechanism explains why the variant is a recognized risk factor for NAFLD. By studying this gene, scientists are gaining a clearer picture of the molecular pathways that govern liver fat storage and the transport of cholesterol and triglycerides throughout the body.
Research Associations and Evidence Strength
The evidence linking the rs58542926 T allele to liver health is considered strong across multiple studies. Meta-analyses have consistently shown that individuals carrying the T allele are at a higher risk for developing NAFLD and, in some cases, more advanced stages of liver disease such as fibrosis. Paradoxically, this same allele is associated with lower levels of circulating serum lipids, such as total cholesterol and LDL cholesterol, and a potentially lower risk of cardiovascular events. This creates a complex clinical picture where a genetic factor that is detrimental to the liver may appear protective for heart health. It is important to note that these are statistical associations observed in large populations. They do not predict an individual's health outcome with certainty, as environmental factors like diet, exercise, and alcohol consumption play significant roles in liver and cardiovascular health.
What You Can Do With This Information
Genetic information regarding rs58542926 is intended for educational purposes and should not be used for self-diagnosis or to make medical decisions. If you are concerned about your liver health or lipid levels, the most effective step is to consult with a healthcare professional. A doctor can order appropriate blood tests, such as liver enzyme panels or lipid profiles, and perform clinical evaluations to assess your actual health status. Because this variant is associated with metabolic traits, your clinician may discuss lifestyle modifications, such as dietary changes or physical activity, which are standard approaches for managing liver fat. Never change your medication or health regimen based on genetic test results without first speaking to your doctor or a pharmacist. They can provide personalized guidance based on your full medical history and current clinical needs.
How common is this variant?
The frequency of the T allele varies significantly by ancestry, with higher prevalence generally observed in European populations compared to other groups. Population-specific data can be found in large-scale genomic databases like gnomAD.
Frequently asked questions
Does having the T allele mean I will get fatty liver disease?
No, having the T allele does not guarantee you will develop fatty liver disease. It is a risk factor, meaning it increases the statistical likelihood, but environmental factors like diet, weight, and lifestyle are major contributors to liver health.
Is the rs58542926 variant the same as the PNPLA3 variant?
No, they are different genetic variants in different genes. Both are well-known risk factors for NAFLD, but they operate through different biological mechanisms in the liver.
Should I get a liver scan if I have the T allele?
You should discuss your genetic results with your doctor. They will determine if a liver scan or other diagnostic tests are necessary based on your physical exam, blood work, and overall health history.
Why is the T allele considered 'protective' for heart health?
The T allele is associated with lower levels of circulating lipids like LDL cholesterol. While this is generally favorable for cardiovascular health, it is a trade-off because the same mechanism causes fat to be retained in the liver.
Sources & further reading
Educational information only, last refreshed 9/27/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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