PLA2R1 rs2247113: Genetics and Strabismus Risk
The single nucleotide polymorphism rs2247113 is an intronic DNA variation located within the PLA2R1 gene on chromosome 2. Recent large-scale genome-wide association studies have identified this variant as being significantly associated with the risk of developing strabismus in individuals of African ancestry. Rather than serving as a direct diagnosis, this variant acts as a statistical genetic marker that sheds light on the complex biological architecture of childhood ocular alignment.
What each genotype means
Typical risk profile
You carry two copies of the common G allele at this locus in the PLA2R1 gene. Large-scale multi-ancestry association studies have not identified an increased statistical likelihood of strabismus associated with this genotype compared to general population averages. Because vision alignment is complex and influenced by many developmental and lifestyle factors, having this typical genotype does not prevent vision disorders.
Carried by approximately 89% to 90% of individuals of African ancestry and greater than 99% of individuals of European or Admixed American ancestry.
Moderately increased strabismus association
You carry one copy of the A allele at this PLA2R1 intronic locus. Research from diverse cohorts, including the All of Us Research Program, has statistically linked this minor allele with an increased risk of strabismus specifically in populations of African ancestry. This finding represents a modest statistical association rather than a clinical diagnosis, and many people with this genotype never develop ocular alignment issues.
Carried by approximately 10% of individuals of African ancestry, but found in fewer than 1% of individuals of Admixed American or European ancestry.
Increased strabismus association
You carry two copies of the A allele at rs2247113 in the PLA2R1 gene. Published multi-ancestry genome-wide studies associate this allele with a higher statistical risk of developing strabismus, an association established primarily in cohorts of African ancestry. Genetic variants contribute only a small fraction of overall risk, and this result does not indicate or diagnose any visual impairment.
Found in less than 1% of individuals of African ancestry and is exceptionally rare in other populations.
Genomic Location and Variant Characteristics
The single nucleotide polymorphism rs2247113 is situated on chromosome 2 within the first intron of the PLA2R1 gene, which encodes phospholipase A2 receptor 1. At this specific genomic position (GRCh38 coordinate chr2:160046487), the standard reference allele is guanine (G), which can alternate with adenine (A). Because it resides in an intronic non-coding region rather than an exon, rs2247113 does not directly alter the amino acid sequence of the encoded PLA2R1 protein. Instead, non-coding variations like this often act by subtly influencing transcriptional regulation, pre-mRNA alternative splicing, or chromatin structure. In genomic association mapping, rs2247113 is also found in strong linkage disequilibrium with nearby non-coding markers in the same locus, such as rs2667037 and rs2715926, meaning these variants are frequently inherited together across generations.
Function of the PLA2R1 Gene
The PLA2R1 gene provides instructions for producing phospholipase A2 receptor 1, a multi-domain transmembrane receptor belonging to the mannose receptor family. This receptor functions primarily to bind and clear extracellular secretory phospholipases (sPLA2 enzymes), thereby modulating lipid signaling cascades, cell proliferation, senescence, and inflammatory pathways. While PLA2R1 is widely celebrated in clinical medicine as the primary autoimmune target in idiopathic membranous nephropathy—a distinct kidney disorder—it is also expressed in diverse tissues throughout the body, including neural and vascular systems. Its potential involvement in ocular development is an emerging area of research, where lipid mediator signaling and extracellular matrix regulation are hypothesized to contribute to the fine-tuned neuromuscular development required for coordinated extraocular muscle alignment.
Scientific Evidence and the Link to Strabismus
Strabismus is a common visual condition characterized by ocular misalignment, where the eyes do not focus synchronously on the same point. Although strabismus has long been known to possess significant heritability, pinpointing clear common genetic risk factors across diverse ancestral groups has historically been difficult. In an extensive genome-wide association study utilizing diverse cohort data from the All of Us Research Program, researchers evaluated common and rare variants across multiple ancestral backgrounds. The study identified the PLA2R1 locus—specifically marked by rs2247113 alongside linked SNPs rs2667037 and rs2715926—as reaching genome-wide statistical significance (P = 2.77 × 10^-8) for strabismus susceptibility specifically within the African ancestry cohort. Because this signal emerged from an initial discovery cohort, geneticists classify the evidence strength as moderate, emphasizing the need for independent replication in other diverse cohorts.
Population Frequency and Ancestry Differences
A critical finding of recent association research is that the risk allele for rs2247113 exhibits substantial frequency differences among global populations. In individuals of African genetic ancestry, the minor A allele occurs at an estimated frequency of approximately 5.5% (MAF ≈ 0.055), making it a well-represented common variant. By contrast, the A allele is extremely rare in other populations; it is present at around 0.5% in Admixed American cohorts and falls below 0.03% in European ancestry populations. Because the allele frequency was under the 1% threshold required for robust genome-wide testing in European cohorts, cross-ancestry statistical replication could not be performed in those groups. These population-specific differences illustrate why including diverse populations in genetic discovery is essential for detecting clinically relevant variants.
Clinical Meaning and Practical Takeaways
Finding that your genotype carries the rs2247113 A allele does not mean that you or your child will inevitably develop strabismus. Strabismus is a multifactorial trait influenced by polygenic architecture, cranial nerve development, refractive errors such as hyperopia, and environmental influences. The statistical association identified for rs2247113 indicates a modest increase in relative risk rather than deterministic causality. Genetic results for this variant cannot diagnose an eye condition or dictate medical treatment. If you have concerns regarding ocular alignment, double vision, or visual milestones in children, you should consult an ophthalmologist or optometrist for a comprehensive, standard clinical eye examination.
How common is this variant?
The minor A allele occurs at a frequency of approximately 5.5% in populations of African ancestry, but is rare in other groups, with frequencies of roughly 0.5% in Admixed Americans and less than 0.03% in Europeans.
Frequently asked questions
What is the rs2247113 genetic variant?
The rs2247113 variant is an intronic single nucleotide polymorphism located in the PLA2R1 gene on chromosome 2. It involves a single DNA letter change from guanine (G) to adenine (A) that serves as a statistical marker for ocular alignment studies.
Does having the rs2247113 A allele mean I will develop strabismus?
No. Strabismus is a complex condition shaped by multiple genetic and environmental factors. Carrying the A allele only confers a modest statistical association in specific ancestry groups and is not deterministic.
Why was rs2247113 only identified in people of African ancestry?
The minor A allele is relatively common in individuals of African genetic descent (around 5.5%), but occurs at frequencies well below 1% in most other ancestries. Because genome-wide association studies typically analyze common variants, it could only be reliably evaluated in the African ancestry cohort.
Is rs2247113 related to kidney disease caused by PLA2R1?
While PLA2R1 is widely known as a major autoantigen in membranous nephropathy, rs2247113 was specifically highlighted in recent research for its association with strabismus. Separate, distinct coding and non-coding variants in PLA2R1 have been investigated for autoimmune kidney phenotypes.
Can a genetic test for rs2247113 replace an eye exam?
No, DNA testing cannot diagnose strabismus or evaluate visual function. Eye alignment and visual acuity must be evaluated directly through clinical examination by an eye care specialist, such as an ophthalmologist or optometrist.
Sources & further reading
Educational information only, last refreshed 9/12/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Variant identified in the PLA2R1 intronic region linked to genetic susceptibility for strabismus in individuals of African ancestry.
Strabismus-associated intronic variant located within the PLA2R1 locus identified through large-scale diversity cohort analysis.