SHBG rs6258: What Your Genotype Means
The rs6258 variant is a specific change in the DNA sequence of the SHBG gene, which provides instructions for making a protein that transports sex hormones in the blood. Research has associated this variant with differences in circulating serum testosterone concentrations in men.
What each genotype means
Typical SHBG function
This is the most common genotype for this variant. Research indicates that individuals with this profile typically exhibit standard SHBG-testosterone binding affinity, which is associated with baseline serum testosterone regulation in men.
This is the major allele genotype and is found in the vast majority of the global population.
Altered SHBG binding affinity
Carrying one copy of the T allele may influence the affinity of the SHBG protein for binding testosterone. Studies suggest this variant can affect measured free testosterone fractions, though clinical significance varies between individuals.
This heterozygous genotype is relatively uncommon, occurring in a small percentage of the population consistent with the reported minor allele frequency.
Reduced SHBG binding affinity
This genotype, also known as the p.P185L missense variant, is associated with altered SHBG protein structure and reduced binding affinity for testosterone. In some clinical reports, this homozygous state has been linked to very low SHBG levels and, in rare cases, endocrine-related presentations; please discuss any hormone-related concerns with your clinician.
This homozygous genotype is rare, with the T allele occurring at a global frequency of approximately 0.28%.
Understanding the rs6258 Variant
The rs6258 variant is a single-nucleotide polymorphism (SNP) located within the SHBG gene on chromosome 17. Specifically, this variant is a non-synonymous change in exon 4, meaning it results in an amino acid substitution (p.P185L) in the resulting protein. Because this change occurs in the coding region of the gene, it has the potential to alter the structure or function of the sex hormone-binding globulin protein itself. Scientists track this specific location in the human genome to understand how minor variations in DNA sequence contribute to the diversity of physiological traits observed across different individuals. While many SNPs have no observable effect, rs6258 is of interest to researchers because it sits in a region critical for the protein's ability to bind and transport hormones.
The Role of the SHBG Gene
The SHBG gene encodes the sex hormone-binding globulin protein, which is primarily produced in the liver. This protein plays a vital role in the endocrine system by binding to sex steroids, including testosterone and estrogen, and transporting them through the bloodstream. By binding these hormones, SHBG regulates the amount of 'free' or bioavailable hormone that can enter target cells and exert biological effects. Because SHBG acts as a carrier, its concentration and binding affinity are key factors in determining the overall hormonal balance in the body. Variations in the SHBG gene can influence not only the total amount of protein produced but also how effectively that protein interacts with its target hormones, potentially impacting reproductive and metabolic health.
Research Associations and Evidence Strength
Scientific research, including large-scale genome-wide association studies (GWAS), has identified a statistical link between rs6258 and serum testosterone concentrations in men. Studies have suggested that this variant may affect the affinity of the SHBG protein for testosterone, which in turn influences the measured fraction of free testosterone in the blood. However, the evidence strength for this association is currently considered limited. While some studies have found significant correlations, the biological impact can be complex and may be influenced by other genetic and environmental factors. It is important to note that these findings are based on population-level statistical associations and do not imply a direct cause-and-effect relationship for every individual. Further research is required to fully understand the clinical significance of this variant.
Population Frequency
The rs6258 variant is relatively rare in the general population. According to available data, the Global Minor Allele Frequency (GMAF) is approximately 0.002755. This means that the variant allele is not commonly found across most ancestral groups. Because the frequency is low, the majority of individuals will carry the common (reference) genotype. Population frequencies can vary significantly based on ancestry, and researchers continue to study these distributions to better understand the genetic architecture of hormone regulation across diverse human populations.
Interpreting Your Genetic Information
If you have information about your rs6258 genotype, it is important to view it within the context of current scientific understanding. This variant is a subject of ongoing research and is not used for routine clinical diagnosis or medical decision-making. Genetic associations are statistical in nature and do not predict individual health outcomes. If you have concerns about your hormone levels, reproductive health, or metabolic markers, you should consult with a qualified healthcare professional or an endocrinologist. They can provide appropriate testing and interpret results based on your personal medical history and clinical symptoms. Never use genetic data to make changes to your health regimen or to self-diagnose, as individual health is influenced by a complex interplay of genetics, lifestyle, and environment.
How common is this variant?
The rs6258 variant is rare, with a Global Minor Allele Frequency (GMAF) of approximately 0.002755.
Frequently asked questions
What does the rs6258 variant do?
The rs6258 variant is a change in the SHBG gene that may alter the structure of the sex hormone-binding globulin protein. This change is statistically associated with differences in how the protein binds to testosterone in the blood.
Is rs6258 associated with any diseases?
While some studies have explored links between SHBG variants and conditions like polycystic ovary syndrome or type 2 diabetes, rs6258 is primarily studied for its association with testosterone levels. It is not currently used as a diagnostic marker for any specific disease.
Should I be worried if I have the T allele?
Genetic variants are common and do not necessarily indicate a health problem. The association between rs6258 and hormone levels is based on population statistics, not individual predictions; you should discuss any health concerns with your doctor.
Can I change my SHBG levels through diet?
SHBG levels are influenced by many factors, including genetics, age, weight, and overall metabolic health. If you are concerned about your hormone levels, consult a healthcare provider to discuss evidence-based lifestyle or medical interventions.
Sources & further reading
Educational information only, last refreshed 9/21/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs6258?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in SHBG
Genetic polymorphism in SHBG associated with circulating sex hormone-binding globulin concentrations and polycystic ovary syndrome susceptibility.
A polymorphism in the SHBG gene often analyzed in the context of metabolic health and exercise-related hormonal profiles.
This variant in the sex hormone-binding globulin gene is associated with an altered risk of recurrent pregnancy loss in women.
The minor allele of this intronic variant is thought to modulate testosterone binding to SHBG and influence the risk of recurrent pregnancy loss.