STAT6 rs1004425: What Your Genotype Means
rs1004425 is an intronic single nucleotide polymorphism located in the STAT6 gene, which encodes a key transcription factor in type 2 immune signaling. This variant has been investigated as a tag SNP for subtle differences in downstream signal transduction following IL-4 and IL-13 stimulation in atopic individuals. Current published evidence shows only limited, population-level statistical associations with atopic traits rather than direct causal effects.
What each genotype means
Typical STAT6 signaling baseline
This genotype represents the most frequently observed version of this genomic location. Research indicates that individuals with this genotype do not carry the specific allele associated with modulated STAT6 activity levels observed in some atopic studies.
Carried by the majority of individuals in many global populations, though specific frequencies vary significantly by ancestry.
Modulated STAT6 signaling potential
Carriers of this genotype possess one copy of the variant allele, which has been studied for its potential to modulate STAT6-mediated responses to IL-4 and IL-13 signaling. This variant is often investigated in the context of atopic traits; however, the clinical significance remains limited and associations are not consistently observed across all populations.
Carried by roughly 1 in 3 to 1 in 4 people of European ancestry, though prevalence is lower in many East Asian populations.
Altered STAT6 signaling potential
Individuals with this genotype carry two copies of the variant allele, which is associated with modulated downstream activity of the STAT6 protein. While this variant is studied in the context of atopic conditions, its influence is complex and evidence linking it to specific clinical outcomes remains limited; it should not be used to predict or diagnose atopic disease.
Carried by a smaller subset of the population, often observed in approximately 5% to 8% of individuals of European ancestry.
Genomic Context and Variant Characteristics
The single nucleotide polymorphism rs1004425 is situated within an intronic region of the STAT6 gene on chromosome 12q13.3. As a non-coding variant, it does not directly alter the amino acid sequence of the encoded protein. Instead, variants in this region often serve as genetic markers or tag SNPs that correlate with nearby regulatory elements influencing gene transcription or splicing. In genomic research, intronic variants in STAT6 are frequently evaluated to determine whether common genetic variation modulates baseline immune reactivity or expression levels of downstream inflammatory mediators.
The Biological Role of STAT6
STAT6 (Signal Transducer and Activator of Transcription 6) is a vital transcription factor in the immune system, particularly within the type 2 helper T-cell (Th2) response pathway. When extracellular cytokines such as interleukin-4 (IL-4) or interleukin-13 (IL-13) bind their respective receptor complexes, receptor-associated Janus kinases (JAKs) phosphorylate STAT6. Phosphorylated STAT6 forms dimers, translocates into the cell nucleus, and activates the transcription of target genes essential for B-cell class switching to immunoglobulin E (IgE) and allergic inflammation.
Current Scientific Evidence and Clinical Strength
Multiple genome-wide association studies (GWAS) and candidate gene studies have linked common genetic variations across the STAT6 locus with atopic dermatitis, asthma, elevated total serum IgE, and allergic rhinitis. For rs1004425 specifically, scientific evidence remains limited. While it acts as a tag marker for differential cytokine responsiveness in some cohorts, effect sizes are modest and findings can vary across ancestries. Unlike rare monogenic gain-of-function missense mutations that cause severe primary atopic disorders, common variants like rs1004425 convey only subtle statistical shifts in polygenic susceptibility.
Population Distribution and Allele Frequencies
Data from large population sequencing resources, including gnomAD and the 1000 Genomes Project, demonstrate that rs1004425 is a common polymorphism in multiple human populations. The minor allele frequency (MAF) typically ranges between 0.20 and 0.28 among European ancestries, meaning that heterozygous and homozygous alternate genotypes are frequently encountered in healthy individuals. Allele frequencies fluctuate across global populations, underscoring that background linkage disequilibrium patterns can alter how strongly this tag variant associates with traits in different ancestral groups.
Practical Implications for Consumers
A genotype result for rs1004425 cannot diagnose asthma, eczema, or any allergic condition, nor does it predict whether an individual will develop atopic symptoms. Environmental triggers, microbiome diversity, barrier function, and hundreds of other genetic loci collectively shape allergic disease risk. Consumers should treat this information strictly as an educational look into polygenic immune variation. Anyone experiencing allergic symptoms or evaluating targeted therapies—such as IL-4 receptor or JAK pathway inhibitors—must discuss their management and dosing directly with a qualified healthcare provider.
How common is this variant?
The minor allele frequency for rs1004425 ranges between approximately 0.20 and 0.28 in European ancestral populations, making both heterozygous and homozygous alternate genotypes common in the general population.
Frequently asked questions
Does having the rs1004425 variant mean I will get asthma or eczema?
No. rs1004425 is a common genetic marker with limited statistical association to atopic traits, not a deterministic cause of disease. The vast majority of people carrying the variant never develop severe allergic disorders, as lifestyle, environment, and many other genes also play critical roles.
How does rs1004425 differ from severe STAT6 mutations?
Severe primary atopic disorders are caused by rare, highly penetrant germline gain-of-function missense mutations in STAT6 that constitutively activate downstream pathways. In contrast, rs1004425 is a common non-coding variant that only subtly modulates signal transduction within normal physiological ranges.
Can rs1004425 tell me if I should take allergy medications?
No, this genetic variant cannot be used to determine whether you need allergy medications or how you will respond to them. Decisions regarding asthma inhalers, antihistamines, biologics, or any other therapies must be made in consultation with a physician or clinical pharmacist based on clinical symptoms.
Where is rs1004425 located in the human genome?
rs1004425 is located in an intronic (non-coding) sequence of the STAT6 gene on chromosome 12. Because it does not alter protein-coding sequence, researchers primarily study it as a marker that may correlate with gene expression or nearby regulatory elements.
Sources & further reading
Educational information only, last refreshed 9/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Intronic variant in STAT6 associated with elevated serum IgE levels and food allergy susceptibility.
An established intronic variant in STAT6 that enhances transcriptional activity and correlates with elevated serum total IgE levels and allergic rhinitis.
Intronic regulatory polymorphism in STAT6 associated with elevated serum IgE levels and mucosal allergic reactivity.
Non-coding variant in the key Th2 signaling transducer STAT6, frequently linked to elevated serum IgE levels and allergic rhinitis risk.
This variant is linked to the clinical phenotype of eosinophilic esophagitis, reflecting the role of immune regulation in the disease.