PRSS56 rs11145465: Refractive Error and Eye Growth
rs11145465 is a common single nucleotide polymorphism located in the genomic region adjacent to the PRSS56 gene on chromosome 2. Genome-wide association studies have identified statistical associations between this locus and quantitative ocular metrics, including ocular axial length, spherical equivalent, and general refractive error. However, because its individual statistical impact is modest and complex vision traits are shaped by hundreds of loci alongside lifestyle factors, evidence linking this single variant directly to noticeable changes in vision remains limited.
What each genotype means
Typical refractive development
Carrying two copies of the C allele is associated in population-level genome-wide association studies with average ocular axial length and baseline risk for common refractive errors such as myopia. Because this variant exerts only a modest regulatory effect within a complex polygenic architecture, carrying this genotype does not determine whether you will require vision correction. Regular comprehensive eye examinations remain standard for monitoring vision changes.
Carried by approximately 25% to 35% of individuals of European ancestry, and found at higher frequencies in East Asian populations.
Modest axial elongation tendency
Carrying one copy of the T allele is associated with slight statistical shifts in ocular axial length and spherical equivalent in international refractive error studies. This variant operates as one of hundreds of small-effect genetic contributors to ocular shape and development, meaning its individual influence on visual acuity is minor. Routine eye checks are recommended to evaluate and manage your personal prescription needs.
Carried by roughly 45% to 50% of people of European ancestry, representing the most common genotype in European cohorts.
Modest axial elongation tendency
Carrying two copies of the T allele has been linked in population genetics research to small differences in ocular axial growth and refractive error compared to the baseline genotype. While PRSS56 plays a role in ocular growth pathways, common non-coding variants like this one have subtle effects that interact broadly with other genetic and environmental factors like near work and outdoor exposure. Your actual refractive status is best assessed through regular visits to an eye care specialist.
Carried by approximately 15% to 25% of individuals of European ancestry, but observed at considerably lower rates in East Asian populations.
Genomic Location and Variant Characteristics
The single nucleotide polymorphism rs11145465 is situated on human chromosome 2, positioned in close intergenic proximity to the PRSS56 gene. PRSS56 encodes serine protease 56, an enzyme with a peptidase S1 domain active during ocular morphogenesis. Polymorphisms in non-coding regulatory flanking regions like rs11145465 often act as proxy markers or regulatory quantitative trait loci (eQTLs) rather than direct protein-altering mutations. In large meta-analytic cohorts, rs11145465 is documented with alleles T and C. Because it resides outside the primary coding exons, the variant does not truncate or directly alter the primary amino acid sequence of the protease enzyme. Instead, scientific interest in rs11145465 stems from its linkage disequilibrium with neighboring functional elements that fine-tune retinal transcript levels. Researchers identify such non-coding variants to track how subtle shifts in gene regulation might nudge physical parameters, such as the vitreous chamber depth or overall corneal curvature, over the course of eye maturation.
Biological Role of the PRSS56 Gene in Eye Development
The PRSS56 gene encodes a secreted trypsin-like serine protease primarily expressed within retinal Müller glia cells and developing retinal progenitor pools. Extensive translational and animal models demonstrate that PRSS56 functions as a critical intrinsic signal directing postnatal ocular axial growth. When severe loss-of-function mutations disrupt PRSS56 in humans or animal models, eye growth is severely restricted, causing conditions such as nanophthalmos and posterior microphthalmos characterized by an abnormally short axial length and extreme hyperopia (farsightedness). Conversely, controlled experimental overexpression of PRSS56 stimulates axial elongation, causing the eye to grow too long from front to back, a defining physical hallmark of myopia (nearsightedness). In typical populations, common variants surrounding PRSS56 appear to modulate the efficiency of ocular axial elongation subtly rather than eliminating protease activity altogether. This tight regulatory balance illustrates how PRSS56 acts as a biological rheostat during child development, balancing focal distance against ocular dimensions.
GWAS Associations and Strength of Evidence
Large international consortia, including the Consortium for Refractive Error and Myopia (CREAM) and the UK Biobank, have identified the PRSS56 locus in genome-wide association studies evaluating spherical equivalent and ocular axial length. Studies report rs11145465 as a marker associated with slight shifts in refractive error measurements. However, the evidence strength for rs11145465 specifically remains classified as limited. While the statistical correlation between variation at the PRSS56 locus and axial length reaches genome-wide significance across meta-analyses, the effect size contributed by rs11145465 alone is very small, accounting for only a fraction of a diopter. Furthermore, refractive phenotypes are highly polygenic, involving hundreds of distinct loci interacting simultaneously. Consequently, carrying a particular allele at rs11145465 does not determine clinical myopia or hyperopia in an individual, and functional studies are ongoing to disentangle whether rs11145465 is a true causal variant or merely tracking a nearby functional variant.
Population Frequency and Ancestry Differences
Allele frequencies for rs11145465 exhibit clear differences across global ancestral populations, which is an important consideration when evaluating genetic risk scores. In populations of European ancestry, the minor allele frequency (MAF) is high, typically hovering between 0.40 and 0.50, meaning both alleles are widely and almost evenly distributed among individuals. In contrast, data from continental genomics repositories indicate that the minor allele occurs at significantly lower frequencies across East Asian and certain African populations. Because linkage disequilibrium architecture varies between distinct ancestral groups, a marker that associates strongly with a trait in European cohorts may not tag the same causal regulatory variation in other backgrounds. Researchers caution that findings for rs11145465 cannot be generalized uniformly across all ancestral groups without multi-ancestry fine-mapping and validation.
Clinical Interpretation and Limitations
It is critical to distinguish between rare Mendelian mutations in PRSS56 and common polymorphisms like rs11145465. Rare coding mutations in PRSS56 cause rare developmental conditions like nanophthalmos, which present with major structural abnormalities and extreme hyperopia detectable early in childhood. In contrast, common variants like rs11145465 simply represent natural human genetic diversity and do not diagnose any clinical disorder. A person’s refractive error—whether they develop myopia, hyperopia, or maintain 20/20 vision—is heavily influenced by visual behaviors, such as time spent outdoors during childhood, sustained close-work activities, and lighting conditions, along with cumulative polygenic background. Learning one’s rs11145465 genotype cannot replace standard clinical refraction testing, nor does it predict the precise prescription an optometrist or ophthalmologist might measure. Routine comprehensive eye examinations remain the standard of care for assessing ocular health and correcting vision.
How common is this variant?
The minor allele frequency for rs11145465 ranges between approximately 0.40 and 0.50 in populations of European descent, while it is observed at substantially lower frequencies in East Asian and African populations.
Frequently asked questions
Does having the rs11145465 variant mean I will need glasses?
No. rs11145465 is associated only with minor, population-level statistical differences in ocular axial length and refractive metrics. Refractive errors such as myopia and hyperopia are shaped by hundreds of genetic variants combined with visual habits and environment, so this single variant cannot predict whether you need corrective lenses.
Is rs11145465 related to severe eye diseases like nanophthalmos?
While severe, rare coding mutations in the PRSS56 gene can cause nanophthalmos or posterior microphthalmos, rs11145465 is a common non-coding variant that is not pathogenic. It is associated with normal continuous variation in eye growth rather than structural malformations.
Can an eye doctor use my rs11145465 genotype to determine my prescription?
No. Genetic testing for variants like rs11145465 has no clinical role in determining or adjusting eyeglasses or contact lens prescriptions. Refractive error is directly measured during a standard comprehensive eye exam using physical optical equipment.
Why do allele frequencies for rs11145465 differ across populations?
Natural human genetic variation naturally drifts and diverges across different geographical ancestries over millennia. The rs11145465 variant is very common in European ancestry groups (40-50% frequency) but occurs less frequently in East Asian and African cohorts, reflecting typical population genetic divergence.
Sources & further reading
Educational information only, last refreshed 9/13/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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