IL1RL1 rs58453446: Understanding This Regulatory Variant
The rs58453446 variant is an intronic genetic change located within the IL1RL1 gene cluster. It is primarily studied for its potential role in modulating the expression of the ST2 receptor, which is a key component of the IL-33 immune signaling pathway.
What each genotype means
Typical ST2 receptor expression
You carry two copies of the common C allele at rs58453446 in the IL1RL1 locus. Research indicates this genotype is associated with baseline levels of the ST2 receptor and an average population risk profile for allergic airway inflammation and asthma. Because this variant acts as an intronic regulatory signal with modest effect, it does not diagnose any respiratory condition.
Carried by approximately 75% to 80% of individuals of European ancestry, and the majority of non-European populations.
Slightly altered ST2 expression
You carry one copy of the minor T allele at rs58453446. Genetic studies show that carrying this single variant allele is associated with subtle differences in IL1RL1/ST2 expression and a modest shift in statistical risk for allergic airway traits. This is an exploratory, limited-evidence association and does not cause or diagnose respiratory disease on its own.
Found in approximately 20% to 22% of individuals of European ancestry; less common in East Asian and African populations.
Altered ST2 receptor expression
You carry two copies of the minor T allele at rs58453446 in the IL1RL1 region. Published findings suggest this homozygous genotype is linked to altered expression of the ST2 receptor pathway involved in type 2 allergic airway inflammation. The overall clinical impact remains limited and exploratory, meaning it reflects a statistical predisposition rather than a definitive medical outcome.
Present in roughly 1% to 2% of people of European ancestry and rare in most other global populations.
What is rs58453446?
The rs58453446 variant is a single nucleotide polymorphism (SNP) situated within the IL1RL1 gene. In genetics, an intronic variant like this one is located in a non-coding region of the gene, meaning it does not directly provide instructions for building a protein. Instead, such variants often function as regulatory elements. These elements act like switches, influencing how much of a specific protein is produced or when that production occurs. Because rs58453446 sits within the IL1RL1 locus, researchers investigate it to see if it alters the expression of the ST2 receptor. By studying these regulatory regions, scientists aim to understand how subtle changes in our DNA sequence can influence biological processes, such as the body's inflammatory response, without changing the structure of the proteins themselves.
The Role of the IL1RL1 Gene
The IL1RL1 gene provides instructions for creating the ST2 receptor, which is essential for the IL-33 signaling pathway. This pathway is a critical mediator that links environmental stress signals to type 2 immune responses. The gene produces two main forms of the receptor: a membrane-bound form (ST2L) and a soluble form (sST2). The membrane-bound form acts as a receptor for IL-33, promoting immune activity, while the soluble form acts as a decoy receptor. By binding to IL-33, the soluble decoy receptor can dampen excessive inflammation. Because of this dual role, the IL1RL1 gene is a major focus in studies regarding immune regulation, tissue homeostasis, and repair. Variations in this gene can potentially shift the balance between these two forms, thereby influencing how the body manages inflammation and responds to immune triggers.
Research Associations and Evidence
Current research into the IL1RL1 locus has identified various SNPs that function as expression quantitative trait loci (eQTLs), meaning they are statistically associated with the levels of sST2 protein in the blood. While some variants in this cluster have been linked to asthma and Alzheimer's disease in large-scale genome-wide association studies (GWAS), the evidence for rs58453446 specifically remains limited. Most research in this area highlights that the IL1RL1 region is highly complex, with many variants working together to influence protein levels. It is important to note that statistical associations found in research do not imply a direct cause-and-effect relationship for every individual. Much of the current data is derived from population-level studies, and the functional impact of this specific variant is still being explored by the scientific community to determine its precise biological significance.
What You Can Do With This Information
Genetic information regarding variants like rs58453446 is primarily intended for educational and research purposes. Because the evidence linking this specific variant to clinical outcomes is limited, it cannot be used to predict personal health risks or diagnose conditions. If you have received genetic testing results that mention this variant, it is important to view them in the context of your overall health and family history. You should not make any changes to your lifestyle, diet, or medical treatments based on this information. If you have concerns about your immune health or specific inflammatory conditions, the best course of action is to consult with a qualified healthcare professional. They can provide guidance based on clinical evidence rather than individual genetic markers, which are often only one small piece of a much larger biological puzzle.
How common is this variant?
The rs58453446 variant has a minor allele frequency of approximately 0.12 in European populations according to gnomAD data.
Frequently asked questions
Is rs58453446 associated with a specific disease?
While the IL1RL1 gene is associated with immune-related conditions like asthma and Alzheimer's disease, the evidence for rs58453446 specifically is limited. Current research focuses on its role in regulating protein levels rather than direct disease causation.
Can I use this variant to predict my health?
No, this variant cannot be used to predict your health. Genetic associations are based on population averages and do not account for the complex interplay of environment, lifestyle, and other genetic factors.
What does it mean if I have the G allele?
Having a specific allele is a normal part of human genetic diversity. It simply means you carry a different version of the DNA sequence at that location compared to the reference genome.
Should I talk to my doctor about this SNP?
Generally, there is no need to discuss this specific SNP with your doctor unless it is part of a broader clinical evaluation. If you have health concerns, focus on symptoms and medical history rather than individual genetic variants.
Sources & further reading
Educational information only, last refreshed 10/11/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant in the IL1RL1/IL18R1 locus influences ST2 receptor expression and modifies individual susceptibility to allergic sensitization and asthma.
An intergenic regulatory variant upstream of IL1RL1 that influences circulating soluble ST2 levels and severity of allergic rhinitis.
ST2/interleukin-1 receptor-like 1 variant associated with altered IL-33 signaling and heightened risk for allergic asthma and atopy.
A regulatory variant within the IL1RL1 (ST2) gene locus associated with allergic rhinitis, eosinophil count regulation, and atopic asthma susceptibility.
Intronic regulatory SNP in IL1RL1/ST2 associated with sST2 expression levels and susceptibility to allergic sensitization and asthma.
Variant in IL1RL1 (ST2) associated with allergic inflammation and cytokine production.