What you carry at this position in your DNA and what research says about it.
Glaucoma Risk: 10/10 evidence, 17 publications.
You're viewing every possible genotype for this variant.
None of these is your result. Use the genotype toggle to compare them, then sign up and upload your DNA to see which one is yours.
Sample genotype (not yours): C/C
Higher Glaucoma Risk
Inheriting two copies of the C allele is linked to a thinner retinal nerve fiber layer and an elevated risk of open-angle glaucoma.
What this genotype means: Thinner retinal nerve fiber layer; Increased susceptibility to optic nerve damage; Higher likelihood of needing glaucoma treatment.
Sample genotype (not yours): A/A
Typical Glaucoma Risk
Inheriting two copies of the A allele is associated with a thicker retinal nerve fiber layer and a lower risk of glaucoma.
What this genotype means: Thicker retinal nerve fiber layer; Lower susceptibility to glaucomatous optic nerve damage; Typical baseline risk of vision loss.
Sample genotype (not yours): C/A
Slightly Elevated Glaucoma Risk
Carrying one copy of the C allele is associated with a mild increase in glaucoma risk and intermediate retinal nerve fiber thickness.
What this genotype means: Intermediate retinal nerve fiber layer thickness; Modestly elevated risk of glaucoma; Slightly increased likelihood of requiring eye monitoring.
Gene function and biological role
Gene Function: The SIX6 gene encodes a homeobox transcription factor that plays a critical role in the early development of the eye and the pituitary gland [1]. It is highly active in the developing neural retina and optic chiasm, where it regulates the differentiation of retinal progenitor cells [2]. Proper expression of this gene is essential for the formation of the optic nerve and the maintenance of retinal ganglion cells [1]. Variations or deletions in this gene can disrupt these developmental pathways, leading to structural changes in the eye and susceptibility to optic nerve degeneration later in life [3].
Variant Impact: The rs33912345 variant is a missense mutation in the SIX6 gene that causes an amino acid substitution from histidine to asparagine at position 141 of the protein [1]. This specific change occurs within the highly conserved homeodomain, which is crucial for the protein's ability to bind DNA and regulate downstream genes [2]. The reference C allele encodes histidine, which is associated with reduced retinal nerve fiber layer thickness and a higher risk of primary open-angle glaucoma [4]. Conversely, the variant A allele encodes asparagine, which appears to preserve optic nerve structure and offer protection against glaucomatous damage [5].
Key Insight: The risk allele for glaucoma at this locus is actually linked to a thinner retinal nerve fiber layer even in healthy individuals without any signs of eye disease.
Location: SIX6. Chromosome 14 · 14q23.1 · 60.5 Mb
Estimated prevalence by population
Global 34.8%; European 15.7%; African 78.3%; East Asian 59.5%; South Asian 33.7%; Americas 16.5%; Ashkenazi 24.1%; Finnish 7.4%; Middle Eastern 39.6%; Amish 19.5%.
Estimated CC genotype frequency.
Global 39.4%; European 47.8%; African 20.4%; East Asian 35.3%; South Asian 48.7%; Americas 48.2%; Ashkenazi 50.0%; Finnish 39.6%; Middle Eastern 46.7%; Amish 49.3%.
Estimated CA genotype frequency.
Global 25.8%; European 36.5%; African 1.3%; East Asian 5.2%; South Asian 17.6%; Americas 35.2%; Ashkenazi 26.0%; Finnish 53.1%; Middle Eastern 13.7%; Amish 31.2%.
Estimated AA genotype frequency.
Showing effects for C/C genotype
Organ Systems
Vision & Eye Health
Glaucoma. Evidence: 10/10. Source: PMID 33627673. ~1.2x Higher Risk.
Glaucoma Medication Use. Evidence: 10/10. Source: PMID 31015401. Higher Likelihood.
Refractive Error. Evidence: 6/10. Source: PMID 35022715. Typical.
Lifestyle, Fitness & Aging
Height & Body Size
Height. Evidence: 10/10. Source: PMID 30595370. Slightly Taller.
Showing effects for A/A genotype
Glaucoma. Evidence: 10/10. Source: PMID 33627673. Typical Risk.
Glaucoma Medication Use. Evidence: 10/10. Source: PMID 31015401. Typical Likelihood.
Refractive Error. Evidence: 6/10. Source: PMID 35022715. Higher Likelihood.
Height. Evidence: 10/10. Source: PMID 30595370. Slightly Shorter.
Showing effects for C/A genotype
Glaucoma. Evidence: 10/10. Source: PMID 33627673. Slightly Higher Risk.
Glaucoma Medication Use. Evidence: 10/10. Source: PMID 31015401. Slightly Higher.
Refractive Error. Evidence: 6/10. Source: PMID 35022715. Slightly Higher.
Height. Evidence: 10/10. Source: PMID 30595370. Typical.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Optic nerve development and structural integrity are heavily influenced by the SIX6 gene. Carrying two copies of the C allele results in the histidine-141 version of the protein, which is associated with a thinner retinal nerve fiber layer [1]. This structural difference is present even in healthy individuals and is thought to make the optic nerve more vulnerable to pressure-induced damage over time [2]. Large-scale genetic studies consistently link this genotype to a roughly 1.2-fold increased risk of primary open-angle glaucoma [3]. Consequently, individuals with this genetic profile are also statistically more likely to require antiglaucoma medications later in life [4]. Regular eye examinations and monitoring of intraocular pressure are particularly relevant for managing this genetic predisposition.
Thinner retinal nerve fiber layer; Increased susceptibility to optic nerve damage; Higher likelihood of needing glaucoma treatment.
Sample genotype: AA (Homozygous)
Protection against optic nerve degeneration is a key feature associated with the A allele of this variant. Carrying two copies of the A allele encodes the asparagine-141 version of the SIX6 protein, which supports optimal development of the neural retina [1]. Clinical studies show that individuals with this genotype tend to have a thicker retinal nerve fiber layer, providing greater structural resilience against pressure changes in the eye [2]. This structural advantage translates to a significantly lower risk of developing primary open-angle glaucoma compared to C allele carriers [3]. While typical eye care guidelines still apply, this genetic profile represents a favorable baseline for long-term vision and optic nerve health [4].
Thicker retinal nerve fiber layer; Lower susceptibility to glaucomatous optic nerve damage; Typical baseline risk of vision loss.
Sample genotype: CA (Heterozygous)
Development of the neural retina is sensitive to variations in the SIX6 protein structure. Having one copy of each allele means both the histidine and asparagine versions of the protein are produced, leading to intermediate structural characteristics in the eye [1]. Research indicates that the retinal nerve fiber layer in heterozygous individuals is slightly thinner than in those with the protective AA genotype, but thicker than in those with the CC genotype [2]. This intermediate phenotype translates to a modest increase in the risk of developing primary open-angle glaucoma [3]. While the risk is lower than that of the CC genotype, routine eye health checkups remain a beneficial practice to monitor optic nerve health [4].
Intermediate retinal nerve fiber layer thickness; Modestly elevated risk of glaucoma; Slightly increased likelihood of requiring eye monitoring.
Variants with shared genetic architecture
rs10483727 · SIX6 Gene · Chr 14 · Glaucoma Risk
rs2745572 · FOXC1 Gene · Chr 6 · Glaucoma Risk
rs7916697 · ATOH7 Gene · Chr 10 · Glaucoma Risk
Mutational screening of 10 genes in Chinese patients with microphthalmia and/or coloboma.
Genome-wide association study of medication-use and associated disease in the UK Biobank.
Content updated August 2026.
ReadYourDNA provides educational interpretation of DNA data you already have. It is not diagnostic, not a substitute for professional medical advice, diagnosis, or treatment, and is not intended to diagnose, treat, cure, or prevent any disease. Talk to a clinician before acting on any result.
Raw DNA Data Reports for 23andMe & AncestryDNA · About ReadYourDNA · FAQ · Methodology & Science · Pricing · Support and complaints · Legal & Contact · Health Traits · Pharmacogenomics · Carrier Status · Variant Explorer · The Human Karyotype · Privacy Policy · Terms of Service · Accessibility · Consumer Health Data Privacy · Your Privacy Choices · Editorial Standards · Your Data, Checkable · Sample Report · ReadYourDNA and Promethease compared · What is inside a 23andMe raw data file · What is inside an AncestryDNA raw data file · What a chatbot can and cannot do with your raw DNA file · Where a raw DNA file can still be uploaded in 2026
Written, maintained and operated by Martin Pechhacker, sole proprietor, Vienna, Austria. Trade register GISA 40064420. support@readyourdna.com