PAX6 rs28936677: Understanding the Genetics of Aniridia
The rs28936677 variant is a specific nonsense mutation in the PAX6 gene that leads to the production of a truncated, non-functional protein. This genetic change is associated with congenital aniridia, a condition characterized by the partial or complete absence of the iris.
What each genotype means
Typical PAX6 function
This genotype represents the common, functional version of the PAX6 gene. Individuals with this profile do not carry the specific nonsense mutation associated with congenital aniridia at this location.
This is the most common genotype found in the general population.
PAX6 haploinsufficiency risk
This genotype includes the p.Arg240Ter nonsense mutation, which leads to a truncated PAX6 protein and haploinsufficiency. This variant is highly penetrant and is associated with congenital aniridia and related ocular developmental conditions. Please consult with a clinical geneticist or ophthalmologist to discuss the implications of this finding for your health and family planning.
This variant is extremely rare, with a global frequency of less than 0.00001 in population databases like gnomAD.
PAX6-related ocular condition
This genotype indicates the presence of the p.Arg240Ter mutation on both chromosomes. Given the severe nature of this PAX6 mutation, this profile is associated with significant ocular developmental challenges. Please consult with a medical specialist to discuss clinical management and appropriate care.
This genotype is exceptionally rare and has not been observed at significant frequencies in general population studies.
What is the rs28936677 Variant?
The rs28936677 variant is a single nucleotide polymorphism (SNP) located within the PAX6 gene on the short arm of chromosome 11 (11p13). Specifically, this variant represents a nonsense mutation, often denoted as p.Arg240Ter. In genetic terms, a nonsense mutation introduces a premature stop codon into the DNA sequence. Instead of the cell reading the full instructions to build the complete PAX6 protein, the machinery stops early, resulting in a shortened or truncated protein product. Because PAX6 is a master regulator gene, this truncation often leads to haploinsufficiency, meaning the body does not produce enough functional protein to support normal development. This specific variant is recognized in clinical databases as a high-impact change that disrupts the standard biological function of the gene.
The Role of the PAX6 Gene
The PAX6 gene is widely considered a master regulator of eye development. It provides the essential instructions for building the structures of the eye, including the iris, lens, and retina. Because it acts early in the developmental process, even minor disruptions to its function can have significant consequences for ocular anatomy. Beyond the eye, PAX6 is also involved in the development of the central nervous system and the pancreas. Research has shown that individuals with certain PAX6 mutations may experience systemic effects, such as glucose intolerance or impaired insulin secretion, highlighting the gene's broad influence on human physiology. When one copy of the PAX6 gene is inactivated or mutated, the resulting haploinsufficiency prevents the eye from forming correctly, which is the primary mechanism behind the clinical presentation of congenital aniridia.
Research and Clinical Associations
The association between rs28936677 and congenital aniridia is well-documented in clinical literature. Aniridia is a panocular disorder characterized by iris hypoplasia, which can lead to vision impairment, nystagmus, and congenital cataracts. The evidence for this variant's role in causing aniridia is considered strong, as it follows an autosomal dominant inheritance pattern. This means that an individual only needs one copy of the mutated gene to manifest the condition. While the clinical expression can be highly variable—even among family members with the same mutation—the underlying cause remains the disruption of the PAX6 protein. Current research is exploring potential therapeutic strategies, such as nonsense mutation suppression, which aims to help the cellular machinery read through the premature stop codon to produce a functional protein, though these treatments remain in the experimental stages.
What You Can Do With This Information
If you or a family member have been identified as a carrier of the rs28936677 variant, it is important to understand that this is a highly penetrant genetic finding. This information is primarily used for clinical diagnosis and genetic counseling. It does not provide a roadmap for self-treatment or lifestyle changes. Because aniridia is a complex condition that can affect multiple aspects of ocular health, management requires a multidisciplinary team, including ophthalmologists and geneticists. If you have questions about your genetic results, the most appropriate step is to consult with a board-certified genetic counselor or a medical geneticist. They can help interpret the findings in the context of your personal and family medical history. Never make medical decisions based on raw genetic data without professional guidance, as clinical context is essential for understanding the implications of any genetic variant.
How common is this variant?
The rs28936677 variant is extremely rare in the general population, with a global minor allele frequency (MAF) reported in gnomAD as less than 0.00001.
Frequently asked questions
Is rs28936677 the only cause of aniridia?
No, while PAX6 mutations are the most common cause, aniridia can also result from chromosomal rearrangements at the 11p13 region or mutations in other downstream target genes.
Can this variant be inherited?
Yes, this variant follows an autosomal dominant inheritance pattern. This means an affected parent has a 50% chance of passing the mutation to each of their children.
Does having this variant mean I will have severe vision loss?
Clinical expression is highly variable. While the variant is associated with aniridia, the severity of ocular symptoms can differ significantly between individuals, even within the same family.
Are there treatments for PAX6-related aniridia?
Current management focuses on treating the symptoms, such as using glasses or contact lenses for vision and monitoring for cataracts or glaucoma. Research into gene-based therapies is ongoing but not yet standard clinical practice.
Sources & further reading
Educational information only, last refreshed 9/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in PAX6
Pathogenic loss-of-function nonsense variant in PAX6 resulting in congenital absence of the iris (aniridia) and associated anterior segment dysgenesis.
A high-penetrance single nucleotide substitution disrupting PAX6 function and leading to aniridia and congenital anterior segment dysgenesis.
Nonsense change in PAX6 leading to haploinsufficiency and classical congenital aniridia.
Intronic regulatory polymorphism in the ocular master regulator PAX6 associated with axial length variation and myopia development.
Classical stop-gain variant in PAX6 leading to haploinsufficiency and congenital aniridia with associated foveal hypoplasia and decreased visual acuity.
Pathogenic missense variant in PAX6 causing developmental ocular malformations including aniridia and congenital ocular coloboma.