What you carry at this position in your DNA and what research says about it.
Liver and Heart Health: 10/10 evidence, 69 publications.
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Sample genotype (not yours): C/C
Lower Liver Risk, Typical Cholesterol
Two copies of the common C allele mean your liver efficiently exports fats into your bloodstream. While this keeps your liver healthy and free of excess fat, it results in slightly higher circulating cholesterol levels compared to carriers of the variant.
What this genotype means: Efficient liver fat export; Typical risk of liver disease; Slightly higher blood cholesterol.
Sample genotype (not yours): C/T
Increased Risk of Fatty Liver Disease
One copy of the T variant reduces your liver's ability to export fat, causing triglycerides to build up inside liver cells. This increases your risk of fatty liver disease, even though your blood cholesterol levels may appear lower and healthier.
What this genotype means: Impaired liver fat export; Increased risk of fatty liver; Slightly lower blood cholesterol.
Sample genotype (not yours): T/T
High Risk of Fatty Liver Disease
Two copies of the T variant severely limit your liver's ability to export fat, leading to significant triglyceride accumulation in liver cells. This greatly increases your risk of fatty liver disease and progressive liver injury, despite having very low blood cholesterol.
What this genotype means: Severely blocked liver fat export; High risk of fatty liver and cirrhosis; Significantly lower blood cholesterol.
Gene function and biological role
Gene Function: The TM6SF2 gene encodes transmembrane 6 superfamily member 2, a protein primarily active in the liver and small intestine [1]. It plays a critical role in regulating the secretion of very low-density lipoproteins, which transport lipids from the liver into the bloodstream [2]. By facilitating the lipidation and export of these fat-carrying particles, TM6SF2 helps maintain a delicate balance between liver fat storage and circulating blood lipids [2]. When TM6SF2 function is impaired, the liver is unable to efficiently package and export triglycerides, leading to cellular fat accumulation [1].
Variant Impact: The rs58542926 variant is a missense mutation in the TM6SF2 gene, resulting in a glutamate-to-lysine substitution at position 167 [1]. This amino acid change causes the TM6SF2 protein to misfold, leading to its rapid degradation and a significant loss of normal function [1]. Because the altered protein cannot properly assist in exporting fats, carriers of the T allele experience a dramatic reduction in circulating blood lipids like LDL cholesterol and triglycerides [3]. However, this systemic benefit comes at a cost, as the retained fats build up directly inside liver cells, significantly increasing the risk of fatty liver disease [1].
Key Insight: This variant creates a direct biological trade-off: it lowers your blood cholesterol but traps fat inside your liver cells.
Location: TM6SF2. Chromosome 19 · 19p13.11 · 19.3 Mb
Estimated prevalence by population
Global 88.5%; European 86.1%; African 93.3%; East Asian 85.7%; South Asian 81.6%; Americas 89.4%; Ashkenazi 91.5%; Finnish 88.6%; Middle Eastern 89.4%; Amish 78.4%.
Estimated CC genotype frequency.
Global 11.1%; European 13.4%; African 6.6%; East Asian 13.8%; South Asian 17.5%; Americas 10.3%; Ashkenazi 8.3%; Finnish 11.0%; Middle Eastern 10.3%; Amish 20.2%.
Estimated CT genotype frequency.
Global 0.4%; European 0.5%; African 0.1%; East Asian 0.6%; South Asian 0.9%; Americas 0.3%; Ashkenazi 0.2%; Finnish 0.3%; Middle Eastern 0.3%; Amish 1.3%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Organ Systems
Liver Function & Disease
Fatty Liver Disease. Evidence: 10/10. Source: PMID 24531328. Typical Risk.
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Slightly Higher.
Triglycerides. Evidence: 10/10. Source: PMID 25961943. Slightly Higher.
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 10/10. Source: PMID 29632382. Typical Risk.
Cancer & Oncology
Gastrointestinal Cancers
Liver Cancer. Evidence: 10/10. Source: PMID 34902334. Typical Risk.
Showing effects for C/T genotype
Fatty Liver Disease. Evidence: 10/10. Source: PMID 24531328. ~1.4x Risk.
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Slightly Lower.
Triglycerides. Evidence: 10/10. Source: PMID 25961943. Slightly Lower.
Type 2 Diabetes. Evidence: 10/10. Source: PMID 29632382. Slightly Increased.
Liver Cancer. Evidence: 10/10. Source: PMID 34902334. Increased Risk.
Showing effects for T/T genotype
Fatty Liver Disease. Evidence: 10/10. Source: PMID 24531328. High Risk.
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Lower.
Triglycerides. Evidence: 10/10. Source: PMID 25961943. Lower.
Type 2 Diabetes. Evidence: 10/10. Source: PMID 29632382. Increased Risk.
Liver Cancer. Evidence: 10/10. Source: PMID 34902334. ~2x Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
A pair of common C alleles represents the typical genetic baseline for lipid transport [1]. Your TM6SF2 protein functions at full capacity, allowing your liver to package triglycerides into VLDL particles and release them into circulation [2]. Consequently, you have a significantly lower risk of developing non-alcoholic fatty liver disease and related liver complications like cirrhosis or liver cancer [3]. However, because fats are actively exported into your blood, you may have slightly higher levels of LDL cholesterol and triglycerides compared to those with the T variant [4]. This means maintaining a heart-healthy diet and active lifestyle remains important to manage cardiovascular risk, even though your liver is naturally protected from fat accumulation [4].
Efficient liver fat export; Typical risk of liver disease; Slightly higher blood cholesterol.
Sample genotype: CT (Heterozygous)
Carrying a single T allele creates a complex metabolic trade-off where liver fat increases while blood lipids decrease [1]. Because you carry one copy of the E167K variant, your TM6SF2 protein levels are partially reduced, impairing the export of fat from your liver [2]. This retention of triglycerides inside hepatocytes increases your susceptibility to non-alcoholic fatty liver disease and elevated liver enzymes like ALT [3]. Over time, this fat accumulation can lead to liver inflammation and a higher risk of progressive liver damage [3]. On the other hand, because less fat is released into your bloodstream, you will likely see lower levels of LDL cholesterol and triglycerides on standard blood panels [4]. However, clinical evidence suggests that the increased risk of liver complications generally outweighs the mild cardiovascular protection provided by these lower blood lipid levels [1].
Impaired liver fat export; Increased risk of fatty liver; Slightly lower blood cholesterol.
Sample genotype: TT (Homozygous)
Double copies of the E167K variant lead to a pronounced loss of TM6SF2 protein function [1]. Your liver cells struggle to package and secrete triglycerides, causing fat to accumulate directly within the liver tissue [2]. This severe retention dramatically elevates your risk of non-alcoholic fatty liver disease, liver cirrhosis, and even liver cancer [3]. Standard blood tests will show remarkably low levels of LDL cholesterol, total cholesterol, and triglycerides, which might otherwise suggest excellent cardiovascular health [4]. However, this lipid profile is misleading because it is driven by hepatic fat retention rather than systemic metabolic efficiency [1].
Severely blocked liver fat export; High risk of fatty liver and cirrhosis; Significantly lower blood cholesterol.
Variants with shared genetic architecture
rs73001065 · MAU2 Gene · Chr 19 · Liver and Heart Health
rs12654264 · HMGCR Gene · Chr 5 · Cholesterol and Statin Response
rs12740374 · CELSR2 Gene · Chr 1 · Heart Disease and Cholesterol
The impact of low-frequency and rare variants on lipid levels.
A large electronic-health-record-based genome-wide study of serum lipids.
Content updated August 2026.
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