RFX6 rs339331: Prostate Cancer Risk and HOXB13 Interaction
The rs339331 variant is a single nucleotide polymorphism located within the RFX6 gene. Research indicates this variant is associated with prostate cancer susceptibility by influencing how the HOXB13 protein regulates gene expression.
What each genotype means
Baseline risk profile
This genotype represents the common version of this genetic marker. Research indicates that the T allele at this position is the one associated with increased prostate cancer risk, so carrying two copies of the C allele does not confer the specific risk linked to this variant.
Carried by approximately 36% of people of European ancestry, based on a minor allele frequency of roughly 0.40.
Increased risk association
This genotype includes one copy of the T allele, which has been associated with an increased risk of prostate cancer in some studies. The T allele is thought to increase the binding of the HOXB13 protein to a transcriptional enhancer, which may influence the regulation of the RFX6 gene. This association is considered to have limited evidence strength, and you should discuss any concerns about prostate health with your clinician.
Carried by approximately 48% of people of European ancestry, based on a minor allele frequency of roughly 0.40.
Elevated risk association
This genotype includes two copies of the T allele, which is the variant associated with increased prostate cancer susceptibility in research. The T allele may lead to allele-specific upregulation of the RFX6 gene through enhanced HOXB13 binding. Because the evidence for this specific variant's impact is limited, this result should be interpreted as a statistical association rather than a diagnostic finding.
Carried by approximately 16% of people of European ancestry, based on a minor allele frequency of roughly 0.40.
Understanding the rs339331 Variant
The rs339331 variant is a specific genetic change, or single nucleotide polymorphism (SNP), located on chromosome 6. While it is often discussed in the context of the HOXB13 gene cluster, the SNP itself sits within an evolutionarily conserved region of the RFX6 gene. Specifically, it is found in an intron, which is a non-coding section of the gene that often plays a critical role in regulating how other genes are turned on or off. By sitting in this regulatory region, the variant can influence the biological machinery of the cell, potentially altering the expression levels of nearby genes that are involved in prostate health and development.
The Role of HOXB13 and RFX6
The HOXB13 gene provides instructions for creating a transcription factor, a protein that binds to DNA to control the activity of other genes. This protein is essential for normal prostate development and acts as a tumor suppressor. Research has shown that the rs339331 variant functions as a binding site for the HOXB13 protein. When the risk-associated allele is present, it increases the binding affinity of HOXB13 to a transcriptional enhancer. This process leads to the upregulation of the RFX6 gene. Elevated levels of RFX6 have been observed in human prostate tumors, and studies suggest that this overexpression may contribute to increased cell proliferation, migration, and invasion, which are hallmarks of tumor progression.
Research and Evidence Strength
The association between rs339331 and prostate cancer risk is grounded in functional genomic studies. Evidence suggests that the T allele at this position is linked to higher RFX6 mRNA levels in prostate tumor tissue. While these findings provide a plausible biological mechanism for how the variant might influence cancer risk, the overall evidence strength for this specific SNP as a standalone clinical predictor remains limited. Prostate cancer is a complex, polygenic condition influenced by hundreds of genetic variants, as well as environmental and lifestyle factors. Therefore, while rs339331 is a significant signal in research settings, it is not currently used as a definitive diagnostic tool for individual risk assessment.
Population Frequency
Genetic variants often show significant differences in frequency across various ancestral groups. For rs339331, the minor allele frequency is approximately 0.40 in European populations. This means the variant is relatively common, appearing in a large portion of the population. Because it is a common variant, its presence alone does not imply a high risk of disease; rather, it is one of many small-effect markers that researchers study to understand the broader genetic architecture of prostate cancer susceptibility across different global populations.
Interpreting Genetic Information
It is important to understand that having a specific genotype for rs339331 does not mean an individual will develop prostate cancer. Genetic risk factors are probabilistic, not deterministic. Many people carry risk-associated alleles without ever developing the associated condition, as other factors like age, family history, and lifestyle play major roles. If you are concerned about your prostate health or family history, the most appropriate step is to consult with a healthcare professional or a genetic counselor. They can provide context based on your personal medical history and help you understand what screening or monitoring might be appropriate for you. Never use genetic data to make medical decisions without professional guidance.
How common is this variant?
The minor allele frequency for rs339331 is approximately 0.40 in European populations, making it a relatively common variant.
Frequently asked questions
Does having the rs339331 variant mean I will get prostate cancer?
No. This variant is a risk factor, not a cause. Most people with this variant will not develop prostate cancer, as the disease is influenced by many genetic and environmental factors.
Should I get tested for rs339331?
Routine testing for this specific SNP is not currently recommended for the general public. If you have concerns about prostate cancer, speak with your doctor about standard screening options like PSA tests.
How does rs339331 relate to the HOXB13 gene?
The rs339331 variant is located in a regulatory region that acts as a binding site for the HOXB13 protein. Changes here can affect how HOXB13 regulates other genes, such as RFX6.
Is this variant the same as the HOXB13 G84E mutation?
No. The G84E mutation is a rare, high-risk coding mutation in the HOXB13 gene itself, whereas rs339331 is a common regulatory variant located in the RFX6 gene.
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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