SLC39A8 rs2109673: Understanding This Pleiotropic Variant
The rs2109673 variant is a genetic change located within the SLC39A8 gene, which plays a critical role in how the body transports essential metal ions. Research has linked this variant to a variety of complex human traits, including differences in lipid profiles, blood pressure regulation, and potential risks for inflammatory conditions.
What each genotype means
Typical metal transport function
You carry two copies of the common ancestral C allele, which encodes the baseline form of the ZIP8 metal transporter with alanine at position 391. Individuals with this genotype show standard cellular uptake of essential trace minerals such as manganese and zinc. In population studies, this genotype is not associated with the altered lipid parameters, decreased manganese levels, or heightened inflammatory bowel disease risks observed with the variant allele.
Present in roughly 80% to 88% of individuals of European ancestry and exceeds 99% frequency in East Asian and African populations.
Reduced manganese transport activity
You carry one copy of the missense T allele (p.Ala391Thr), which causes hypofunctional manganese and zinc transport relative to the typical form. Genome-wide association studies have statistically linked this heterozygous status to lower circulating serum manganese concentrations, subtle shifts in lipid markers (such as higher HDL cholesterol), and modestly increased risks for Crohn's disease and cardiovascular traits. Because these are statistical associations derived from large population cohorts rather than direct clinical diagnoses, carrying this genotype does not mean you have or will develop any medical condition.
Carried by approximately 12% to 18% of individuals of European descent, but found in fewer than 1 in 500 individuals of East Asian or African ancestry.
Significantly altered trace metal transport
You carry two copies of the missense T allele, conferring two altered copies of the ZIP8 transporter (p.Thr391 homomer). Large-scale observational studies associate this rare genotype with the lowest mean serum manganese levels across common genotypes, altered protein N-glycosylation patterns, higher HDL cholesterol, and a statistically elevated relative risk for inflammatory bowel disease and blood pressure variability. These multi-trait associations represent broad population-level probabilities across complex traits, and lifestyle, diet, and clinical context remain the primary determinants of health.
Found in approximately 0.5% to 1% of individuals with European ancestry and is exceptionally rare (substantially under 0.05%) in other continental ancestries.
What is rs2109673?
The variant rs2109673 is a single-nucleotide polymorphism (SNP) located within the SLC39A8 gene. In genetics, a SNP represents a variation at a single position in the DNA sequence. This specific variant is often studied alongside other markers in the same gene, such as the well-documented p.Ala391Thr substitution. Because SLC39A8 is highly conserved across vertebrates, even small changes in its DNA sequence can potentially alter the function of the protein it encodes. Scientists track these variants to understand how subtle differences in our genetic code contribute to the wide range of physical and physiological traits observed across the human population. By mapping these variations, researchers aim to build a clearer picture of the genetic architecture underlying complex health-related characteristics.
The Role of the SLC39A8 Gene
The SLC39A8 gene provides instructions for creating a protein known as ZIP8. This protein functions as a metal ion transporter, residing primarily in the plasma membrane of cells. Its main job is to facilitate the uptake of essential divalent metal ions, including manganese, zinc, and iron, into the cell. These metals are vital for numerous biological processes, such as enzyme function and cellular metabolism. When the ZIP8 transporter is functioning correctly, it helps maintain the delicate balance of these minerals within the body. Disruptions in this gene can lead to significant health challenges, as seen in rare, severe conditions like congenital disorders of glycosylation. In the context of common variants like rs2109673, the impact is generally more subtle, potentially influencing the efficiency of metal transport rather than causing a complete loss of function.
Research and Associations
Genome-wide association studies (GWAS) have identified rs2109673 as a pleiotropic variant, meaning it is associated with multiple, seemingly unrelated traits. Research has linked this variant to variations in lipid profiles, such as HDL-cholesterol levels, as well as differences in blood pressure and markers of inflammation. Some studies have also explored its potential connection to inflammatory bowel disease and other complex conditions. However, it is important to note that the evidence for these associations is often described as limited or mixed. While statistical correlations are frequently observed in large datasets, they do not necessarily imply a direct cause-and-effect relationship. Furthermore, the biological mechanisms linking this specific transporter variant to such diverse outcomes are still being actively investigated by the scientific community to determine how metal homeostasis influences these specific health traits.
Population Frequency
The frequency of the rs2109673 variant varies significantly depending on ancestral background. In many European populations, the minor allele is present at a frequency of approximately 6% to 10%. Conversely, this variant is considered very rare in many Asian and African populations. These differences in allele frequency are common in human genetics and highlight the importance of considering ancestry when interpreting genetic data. Because the variant is more common in some groups than others, the observed associations with health traits may also be more pronounced or easier to detect in those specific populations. Researchers use this information to ensure that genetic studies are representative and to avoid making broad generalizations that may not apply equally to all individuals across the globe.
Interpreting Your Genetic Information
If you have information about your genotype for rs2109673, it is important to view it as one small piece of a much larger puzzle. Genetic variants are rarely the sole cause of complex traits like blood pressure or lipid levels, which are heavily influenced by diet, lifestyle, and other environmental factors. You cannot use this information to diagnose yourself with a condition or to predict your future health with certainty. If you are concerned about your blood pressure, cholesterol, or any other health metric, the most effective approach is to consult with a qualified healthcare professional. They can interpret your clinical test results in the context of your overall health history. Never make changes to your medications or health regimen based on genetic data without first discussing these changes with your doctor or a licensed pharmacist.
How common is this variant?
The minor allele (T) frequency is approximately 6-10% in European populations and is very rare in Asian and African populations.
Frequently asked questions
Is rs2109673 a cause of disease?
No, rs2109673 is a genetic variant associated with certain traits in statistical studies, but it is not a direct cause of disease. Complex health conditions are influenced by a combination of many genes, environmental factors, and lifestyle choices.
Can I use this SNP to predict my cholesterol levels?
While this variant has been linked to lipid profiles in research, it cannot be used to accurately predict your personal cholesterol levels. Clinical blood tests ordered by your doctor are the only reliable way to measure your cholesterol.
Should I take supplements because of this variant?
There is no evidence that this variant requires specific supplementation. You should never start or change a supplement regimen based on genetic data without consulting your healthcare provider.
Why do some populations have this variant more often?
Differences in allele frequencies across populations are common and often result from historical migration, genetic drift, and natural selection. These patterns are a normal part of human genetic diversity.
Sources & further reading
Educational information only, last refreshed 10/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant is associated with manganese levels and risk of neurological and inflammatory conditions.
Missense variant (p.Ala391Thr) in SLC39A8 linked to differences in HDL cholesterol, body mass index, blood pressure, and risk of schizophrenia.
Missense variant (p.Ala391Thr) robustly associated with sleep duration and daytime sleepiness in recent large-scale UK Biobank sleep health genome-wide scans.