FOXG1 rs146652416: Understanding Your Genetic Variant
The rs146652416 variant is a rare genetic change located within the FOXG1 gene. Research has identified this specific variant as having a statistically significant sex-specific interaction effect on the thickness of the retinal nerve fiber layer (RNFL).
What each genotype means
Typical retinal nerve thickness
This genotype represents the common baseline state for this variant. Research indicates that individuals with this genotype do not exhibit the specific sex-linked association with retinal nerve fiber layer thickness observed in carriers of the alternative allele.
This is the most common genotype found across global populations.
Potential retinal thickness variation
Carrying one copy of this variant may influence retinal nerve fiber layer thickness, with studies suggesting this effect is dependent on the individual's sex. Because this is a rare variant, the clinical significance of this specific measurement is not fully established and should not be used for diagnostic purposes.
This genotype is rare and observed at very low frequencies in most ancestral populations.
Potential retinal thickness variation
Carrying two copies of this variant may influence retinal nerve fiber layer thickness, with research suggesting a sex-specific interaction effect. As this variant is rare, the long-term implications for eye health are not well-defined, and this finding should be interpreted with caution.
This genotype is extremely rare across all known ancestral populations.
What is rs146652416?
The identifier rs146652416 refers to a single nucleotide polymorphism (SNP), which is a variation at a single position in the DNA sequence. This specific variant is located within the FOXG1 gene. In genomics, SNPs are the most common type of genetic variation among people, and they can act as biological markers that help scientists locate genes associated with specific traits or health conditions. Because rs146652416 is classified as a rare variant, it is not found in the majority of the population. Geneticists study these rare variants to understand how subtle differences in our DNA code might influence physical characteristics or physiological processes. While this variant is cataloged in public databases, its presence does not inherently imply a health condition, but rather serves as a point of interest for researchers investigating the genetic architecture of human traits.
The Role of the FOXG1 Gene
The FOXG1 gene provides the instructions for creating the forkhead box G1 protein. This protein functions as a transcription factor, a type of molecule that acts like a master switch to turn other genes on or off. FOXG1 is particularly critical during early brain development, where it acts as a transcriptional repressor, helping to ensure that neural tissues develop correctly. Because of its essential role in brain formation, mutations that significantly disrupt the function of the FOXG1 gene are known to be associated with FOXG1 syndrome, a rare neurodevelopmental disorder characterized by features such as intellectual disability and epilepsy. However, it is important to distinguish between rare, high-impact mutations that cause clinical syndromes and common or rare SNPs like rs146652416, which are often studied for their more subtle, non-syndromic associations with quantitative traits.
Research and Associations
Current research into rs146652416 has highlighted a statistically significant interaction between this variant and sex regarding the thickness of the retinal nerve fiber layer (RNFL). The RNFL is a layer of nerve fibers in the eye that transmits visual information to the brain, and its thickness is a common metric used in ophthalmology to assess neural integrity. The evidence for this association is currently considered moderate, meaning that while the statistical signal is present in the data, it requires further replication and functional validation to fully understand the biological mechanism. The sex-specific nature of this finding suggests that the influence of this variant on retinal structure may differ between males and females, a common theme in complex trait genetics. As with many findings in the GWAS Catalog, these associations are based on population-level data and do not necessarily predict individual outcomes.
What This Information Means for You
If you have encountered this variant in your genetic data, it is important to maintain a balanced perspective. Genetic associations, particularly those involving rare variants and complex traits like RNFL thickness, are intended for educational and research purposes. They are not diagnostic tools and cannot predict your personal health status or the future health of your eyes. Because the evidence for this specific variant is moderate and the trait is influenced by a wide array of environmental and other genetic factors, this information should not be used to make medical decisions. If you have concerns about your vision or the health of your eyes, the most appropriate step is to consult with an eye care professional, such as an optometrist or ophthalmologist. They can perform clinical examinations that provide actionable information about your ocular health, which is far more reliable than any single genetic marker.
How common is this variant?
The rs146652416 variant is classified as rare, meaning it appears at a very low frequency across most global populations. Specific frequency data can vary significantly by ancestry.
Frequently asked questions
Is rs146652416 associated with FOXG1 syndrome?
No. FOXG1 syndrome is typically caused by rare, high-impact mutations that disrupt the function of the FOXG1 gene. The SNP rs146652416 is a different type of variant associated with quantitative traits rather than the clinical syndrome.
Can I use this SNP to predict my risk of eye disease?
No. This variant is associated with a measurement of retinal thickness in a research context. It is not a diagnostic marker for any eye disease or clinical condition.
What does 'sex-specific interaction' mean?
This means that the effect of the genetic variant on the trait (RNFL thickness) appears to be different in males compared to females. It suggests that biological sex may influence how this specific DNA change affects the body.
Should I be worried if I have this variant?
There is no reason for concern. Genetic variants are common, and most have no significant impact on your daily life. This variant is simply a subject of ongoing scientific study.
Sources & further reading
Educational information only, last refreshed 10/12/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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