rs20541 — IL13 R130Q

Missense variant in IL-13 that enhances Th2 cytokine signaling, elevating serum IgE and increasing risk for atopic dermatitis, allergic rhinitis, and eczema; the minor A allele (Q130) confers risk while the common G allele (R130) is protective for atopic disease

See your personal result for IL13

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

IL-13 R130Q — The Th2 Cytokine Amplifier at the Heart of Atopic Disease

Interleukin-13 is the central cytokine of type 2 immune responses11 type 2 immune responses
Th2 immunity orchestrates anti-parasitic defense and allergic inflammation; it is mediated by T-helper 2 cells, ILC2 innate lymphoid cells, and mast cells, and is characterized by IL-4, IL-5, IL-13, and IgE production. While IL-4 drives central T-cell differentiation, IL-13 executes the peripheral tissue damage that defines atopic dermatitis: it remodels the skin barrier, recruits eosinophils, stimulates IgE production, and alters the skin microbiome. The rs20541 variant lies in the IL13 coding sequence and changes a single amino acid at position 130 of the mature peptide. The minor A allele (Q130, present in ~20% of European chromosomes) produces an IL-13 protein with subtly altered receptor engagement, and this change has measurable consequences for IgE levels and atopic disease risk across multiple populations.

The Mechanism

rs20541 is a missense variant that substitutes glutamine (Q) for arginine (R)22 glutamine (Q) for arginine (R)
The substitution is at position 130 of the mature IL-13 peptide (position 144 in the full precursor including the 18-residue signal peptide); rs20541-A encodes Gln, rs20541-G encodes Arg at a site in helix D of the IL-13 four-helix bundle. IL-13 signals through a two-step receptor assembly: low-affinity binding to IL-13Rα1, then recruitment of IL-4Rα to form the high-affinity Type II receptor complex that drives STAT6 phosphorylation. The Q130 (A allele) variant alters the surface charge near the IL-13Rα1 binding interface; evidence from gene association studies indicates it produces functionally enhanced IL-13 signaling, as reflected in measurably elevated serum IgE across multiple ancestry groups. IL-13 acting through Type II receptors in keratinocytes suppresses the expression of filaggrin and other barrier proteins, directly connecting elevated IL-13 tone to the skin barrier defects central to atopic dermatitis. In the skin of AD patients, IL-13 is the dominant Th2 cytokine in the chronic phase, making the genetic amplification of its activity clinically consequential.

The Evidence

The IL13/5q31 locus is one of the most consistently replicated in allergy genetics, and rs20541 sits within it as the primary coding variant. A 2023 European and multi-ancestry GWAS meta-analysis33 2023 European and multi-ancestry GWAS meta-analysis
Budu-Aggrey et al., Nature Communications; European discovery: ~21,000 AD cases and ~95,000 controls; 23andMe European replication: 2.9 million individuals identified the 5q31 locus at P<10⁻³⁶ for atopic dermatitis, with the G allele (Arg-130) appearing as the protective effect allele (OR≈0.91). The effect is additive: each copy of the A allele (Gln-130) incrementally increases risk. Fine-mapping in Japanese cohorts (pilot n=939, replication n=2,377)44 Japanese cohorts (pilot n=939, replication n=2,377)
Hirota et al. 2020, JACI confirmed rs20541 significantly associated with total serum IgE (a biological measure of Th2 activation), while a separate 3'-UTR variant (rs1295685) tags independent regulatory effects on IL13 expression.

In a Singapore cohort of 1,322 ethnic Chinese55 1,322 ethnic Chinese
Andiappan et al. 2013, Gene, rs20541 was significantly associated with allergic rhinitis, with the homozygous AA genotype carrying OR=1.57 for allergic rhinitis compared to GG. Korean case-control data (631 AD patients, 458 controls)66 (631 AD patients, 458 controls)
Jo et al. 2011 found rs20541 particularly enriched in the allergic-type AD subgroup (elevated serum IgE). A Taiwanese nursing study77 Taiwanese nursing study
OR=3.38 for AA under recessive model; non-atopic hand eczema found the AA genotype carried OR=3.38 for non-atopic hand eczema under a recessive model. The COCOA birth cohort (1,637 Korean children)88 (1,637 Korean children)
Ha et al. 2014 and Lee et al. 2021 showed that GA/AA genotype combined with early antibiotic exposure raised the risk of early-persistent atopic dermatitis to aOR=4.73 — a striking gene-environment interaction indicating that the IL-13 genotype is especially consequential when the early-life microbiome is disrupted.

A 2024 Mendelian randomization study used rs20541 as a genetic instrument to mimic IL-13 inhibition in 563,946 individuals99 IL-13 inhibition in 563,946 individuals
Rukin et al. 2024. Genetically proxied IL-13 inhibition was associated with markedly elevated risk of psoriatic arthritis (OR 37.39) and psoriasis (OR 20.08) — confirming that the same cytokine that protects against psoriasis drives atopy. This finding supports the real-world observation that dupilumab (an IL-4Rα blocker suppressing both IL-4 and IL-13) occasionally triggers psoriasiform skin reactions in a subset of atopic dermatitis patients.

Practical Implications

Carriers of the AA genotype have the highest constitutive IL-13 signaling of the three genotypes. This translates to measurably higher baseline serum IgE, a greater tendency to mount Th2 responses to environmental allergens, and elevated lifetime risk for atopic dermatitis, allergic rhinitis, and eczema. Two biologics directly target the IL-13 pathway: tralokinumab1010 tralokinumab
Anti-IL-13 monoclonal antibody approved for moderate-severe atopic dermatitis; specifically neutralizes IL-13 protein, making it the most direct pharmacological intervention for carriers of the Q130 IL-13 variant (Adbry, anti-IL-13 monoclonal antibody) and dupilumab (Dupixent, anti-IL-4Rα, blocking both IL-4 and IL-13 signaling). Carriers of the A allele — particularly AA homozygotes — are biologically the ideal candidates for IL-13-targeted therapy when their atopic disease is inadequately controlled by conventional treatment. Baseline biomarker measurement (serum IgE, periostin, DPP-4) helps confirm elevated IL-13 pathway activity before initiating biologic therapy.

Interactions

rs20541 interacts with the filaggrin (FLG) null allele ecosystem: IL-13 directly suppresses filaggrin expression through STAT6 signaling, so carriers of both IL-13 Q130 (A allele) and FLG loss-of-function variants face compounding barrier defects — both structural (absent filaggrin) and inflammatory (elevated IL-13 suppressing residual barrier). A compound action should be considered for rs20541-AA combined with FLG null variants (rs61816761, rs558269137, rs372628716).

The rs1801275 variant (IL-4Rα R576Q) alters the IL-4Rα signal transduction unit shared by both IL-4 and IL-13 receptors. Individuals carrying both rs20541-A (enhanced IL-13 ligand) and rs1801275 risk allele (altered receptor) may face additive Th2 dysregulation — documented mechanistic interactions exist for both nodes of the same receptor complex. This interaction is relevant to dupilumab pharmacogenomics, as dupilumab targets IL-4Rα directly.

Drug Interactions

dupilumab dose_adjustment literature
tralokinumab dose_adjustment literature

Genotype Interpretations

What each possible genotype means for this variant.

GG Protective IL-13 Variant Normal

Common IL-13 form with standard Th2 signaling and typical atopy risk

You carry two copies of the G allele (Arg-130) at rs20541, the most common form of IL-13 in all major population groups. Your IL-13 protein functions at baseline Th2 tone — normal IgE production, standard skin barrier IL-13 activity, and population-average risk for atopic dermatitis and allergic rhinitis. This genotype is carried by approximately 62% of Europeans. The G allele appears protective against atopic disease in GWAS meta-analyses but is conversely associated with modestly elevated psoriasis risk compared to A allele carriers, reflecting the opposing roles of IL-13 in Th2 vs Th17-driven inflammatory diseases.

AG Elevated IL-13 Activity Intermediate

One copy of the IL-13 Q130 variant with moderately elevated Th2 signaling and atopic disease risk

IL-13 Q130 (A allele) produces a protein with slightly altered receptor-binding characteristics at the IL-13Rα1 interface. The net functional effect is enhanced STAT6 signaling in keratinocytes and immune cells, leading to measurably higher serum IgE — a reliable biological readout of Th2 immune tone. As a heterozygote you have one Q130 and one R130 allele; the elevated IL-13 activity is intermediate. GWAS data show the atopy risk allele dose-response is linear across GG → AG → AA, consistent with a codominant or additive model.

AA High IL-13 Activity High Risk

Two copies of IL-13 Q130 — highest Th2 signaling load with substantially elevated atopic dermatitis, rhinitis, and eczema risk

As an AA homozygote, both copies of your IL-13 gene produce the Q130 (Gln) protein form. Every IL-13 molecule you secrete carries the altered receptor-binding configuration, and serum IgE — the downstream readout of sustained IL-13-driven B-cell class-switching — is measurably elevated at baseline. In the skin, IL-13 acts through STAT6 on keratinocytes to suppress filaggrin, loricrin, and other structural barrier proteins. Homozygous Q130 activity amplifies this barrier suppression, creating conditions favourable for allergen penetration and sensitization. Gene-environment data from the COCOA birth cohort show the AA/GA combined effect becomes especially pronounced when combined with early antibiotic exposure (aOR=4.73 for early-persistent AD), consistent with the IL-13 genotype shaping how gut and skin microbiome disruption is immunologically interpreted. From a pharmacogenomics standpoint, the AA genotype represents the population most likely to have high-baseline IL-13-pathway biomarkers (IgE, periostin, DPP-4) and is biologically the primary target population for IL-13-directed biologics (tralokinumab) and IL-4Rα inhibitors (dupilumab) when atopic disease is moderate to severe.