PLA2R1 rs2667037: What Your Genotype Means
The genetic variant rs2667037 is a single nucleotide polymorphism located within an intronic region of the PLA2R1 gene on chromosome 2. Genome-wide association studies have identified this marker as a candidate locus linked to susceptibility to strabismus in individuals of African ancestry. While this variant highlights an emerging biological pathway in ocular alignment, it serves as a statistical association rather than a definitive diagnostic test.
What each genotype means
Typical risk profile
You carry two copies of the common G allele at this PLA2R1 locus. Genome-wide studies have not linked this genotype with an increased genetic susceptibility to strabismus. Having this baseline profile does not guarantee eye alignment will develop without issue, as vision traits depend on many genetic and environmental factors.
Carried by the vast majority of individuals across all global ancestries, including roughly 89% to 90% of individuals of African descent and over 99% of people of European and Admixed American ancestries.
Moderately elevated strabismus susceptibility
You carry one copy of the A variant allele in intron 1 of the PLA2R1 gene. Large-scale association research, notably in cohorts of African ancestry, has identified this variant as being statistically associated with higher susceptibility to childhood-onset strabismus (eye misalignment). This finding reflects a statistical association in population studies and is not a clinical diagnosis or a certain predictor of visual misalignment.
Carried by approximately 10% of individuals of African ancestry, while it occurs in fewer than 1% of Admixed American and European populations.
Elevated strabismus susceptibility
You carry two copies of the A variant allele in intron 1 of the PLA2R1 gene. In published genome-wide association studies of African ancestry populations, this variant locus is significantly associated with an increased statistical risk for developmental strabismus. This indicates an increased genetic susceptibility rather than a diagnosis, as strabismus is a multifactorial trait influenced by multiple genes and developmental factors.
Carried by roughly 1 in 300 to 1 in 400 individuals of African ancestry (approximately 0.3%), and it is exceedingly rare in populations of other ancestral backgrounds.
Genomic Location and Variant Characteristics
The rs2667037 polymorphism is situated within intron 1 of the PLA2R1 gene on the long arm of human chromosome 2. As an intronic single nucleotide variant, it does not alter the primary amino acid sequence of the encoded protein directly. Instead, intronic polymorphisms frequently influence organismal biology by altering regulatory elements, splicing efficiency, or local transcription factor binding motifs. In many instances, variants like rs2667037 act as tag SNPs, meaning they sit in high linkage disequilibrium with other untyped functional DNA sequences nearby. Genome mapping projects, including dbSNP and Ensembl, catalogue the alleles at this position across diverse global reference panels. While intronic variation often has subtle or context-specific cellular consequences, characterising these markers provides critical insight into the non-coding architecture of the human genome and helps pinpoint genomic intervals that regulate complex physiological processes such as visual pathway development and neuromuscular coordination in the eye.
The Biological Role of PLA2R1
The PLA2R1 gene encodes phospholipase A2 receptor 1, a large type I transmembrane receptor that belongs to the mannose receptor family. This receptor binds soluble secretory phospholipases A2 (sPLA2) to facilitate their internalization and clearance, thereby dampening downstream inflammatory signaling and lipid mediator production. Beyond receptor-mediated endocytosis, PLA2R1 participates in cellular senescence, cell migration, and tissue homeostasis through transmembrane signal transduction cascades. Although PLA2R1 is widely celebrated in nephrology as a primary autoantigen in autoimmune membranous nephropathy, expression profiling reveals that the receptor is also transcribed across multiple non-renal tissues, including nervous system structures and developing ocular components. In the visual system, tightly calibrated cellular signaling and extracellular matrix maintenance are essential during embryogenesis for the proper morphogenesis and innervation of extraocular muscles. Disruptions in lipid clearance or local signaling pathways governed by PLA2R1 could theoretically perturb tissue scaffolding or neuromuscular signaling required for coordinated binocular vision.
Current Research and Strabismus Associations
Strabismus is a common visual disorder defined by ocular misalignment, impacting roughly 2 to 4 percent of individuals worldwide. Recent genome-wide association studies (GWAS) investigating ocular traits have linked rs2667037, alongside neighboring intron 1 markers such as rs2247113 and rs2715926, to strabismus risk specifically within African ancestry cohorts. This association provides moderate statistical evidence linking the PLA2R1 locus to ocular misalignment phenotypes. However, strabismus is an intrinsically complex, polygenic trait shaped by dozens of subtle genetic influences acting in concert with developmental and environmental factors. Crucially, statistical signals observed in genome-wide association analyses identify elevated statistical odds at a population level rather than single-gene determinism. To date, this genetic signal has shown population-specific characteristics, emphasizing the need for multi-ancestry replication studies to ascertain whether the finding translates to other demographic groups or represents ancestry-specific linkage architecture.
Population Distribution and Genetic Diversity
Genomic databases such as gnomAD and the 1000 Genomes Project demonstrate that allele frequencies at rs2667037 vary noticeably across global ancestral groups. The variant is common in African and African-admixed populations, where its minor allele frequency routinely exceeds 1 percent (MAF > 0.01). In contrast, the frequency of the non-reference allele may be substantially lower or display distinct linkage disequilibrium patterns in European, East Asian, or Indigenous American populations. The divergence of allele distributions between populations underscores why genetic association findings cannot be universally generalized across ancestral lines. Because demographic history, selective pressures, and background haplotypes shape variant frequencies, an association uncovered in an African ancestry cohort requires focused validation in that specific genetic context. Understanding these population genetics differences helps geneticists build inclusive reference catalogs that avoid mischaracterizing common ancestral variations as pathogenic anomalies.
Clinical Utility and Practical Interpretation
Interpreting an individual's rs2667037 genotype requires understanding the boundary between statistical association and clinical diagnosis. Possessing a risk-associated genotype at this locus does not mean a person has or will inevitably develop strabismus, nor does the absence of the allele guarantee perfect binocular alignment. Most individuals carrying the statistical risk allele never develop misaligned eyes, and many who have strabismus do not harbor the variant. Because the overall effect size of any individual non-coding SNP is small, rs2667037 is not suitable as a standalone predictive or diagnostic tool. Routine genetic testing for rs2667037 is not part of standard ophthalmic practice. Visual screening and physical eye examinations conducted by an optometrist or ophthalmologist remain the sole established standards for diagnosing and managing ocular misalignment. Consumers who receive personal genomics reports should treat this information as educational background rather than medical instruction.
How common is this variant?
The rs2667037 variant is common in African and African-admixed ancestry cohorts with a minor allele frequency greater than 0.01, whereas its prevalence is markedly lower or exhibits different linkage patterns across other global populations.
Frequently asked questions
What is strabismus and how does it develop?
Strabismus is a condition in which the eyes do not align properly with each other when focusing on an object, often colloquially called crossed eyes. It arises when the neuromuscular control of the extraocular muscles or visual brain pathways fails to coordinate ocular movement. Both environmental variables and complex genetic factors contribute to its development.
Does having the rs2667037 risk genotype mean I will develop crossed eyes?
No, carrying the risk-associated genotype does not mean you will develop strabismus. Complex traits like ocular misalignment involve many interacting genes alongside environmental influences, and individual SNPs only exert small statistical effects. Many individuals who carry this variant maintain normal binocular vision throughout their lives.
Why is this PLA2R1 association only reported in African ancestry groups?
Genetic association signals frequently depend on the ancestral background of the study cohort because allele frequencies and linkage patterns vary across human populations. The specific GWAS identifying rs2667037 discovered the association in African ancestry cohorts, meaning further research is required to evaluate its effects in other ancestral backgrounds.
Can a genetic test for rs2667037 replace a clinical eye examination?
No, genetic testing for rs2667037 cannot replace an examination by an eye care specialist. Strabismus is diagnosed through direct physical assessments of ocular motility, alignment, and visual acuity. If you or your child experience issues with eye alignment, you should consult an optometrist or ophthalmologist for clinical evaluation.
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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