rs12722489

badMag 4.5

This is a intron variant variant in the IL2RA gene.

Key Literature Trait Associations

Multiple Sclerosis Risk

Intronic variant in IL2RA (CD25), the high-affinity IL-2 receptor alpha chain critical for regulatory T-cell function. The T allele is associated with reduced Treg activity and increased MS risk. IL2RA variants are also associated with type 1 diabetes, suggesting shared autoimmune pathways.

Rangani F et al. “Association of IL2RA and multiple sclerosis risk: A case control, systematic review, and meta-analysis study.” Journal of the Neurological Sciences (2025)

Allele T

OR —

p 4.0e-2

N 51,882

Meta-analysis

multi-ancestry

De Jager PL et al. “Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.” Nature Genetics 41(7):776-782 (2009)

Allele T

OR 1.25

p 1.0e-15

Large GWAS

Hafler DA et al. “Risk alleles for multiple sclerosis identified by a genomewide study.” The New England Journal of Medicine 357(9):851-862 (2007)

Allele T

OR 1.25

p 3.0e-8

N 12,360

Large GWAS

European

Wang LM et al. “Interleukin 2 receptor α gene polymorphism and risk of multiple sclerosis: a meta-analysis.” The Journal of International Medical Research (2011)

Allele T

OR —

p —

N 12,058

Meta-analysis

European

Wang XX et al. “Meta-analysis of the association of IL2RA polymorphisms rs2104286 and rs12722489 with multiple sclerosis risk.” Immunological Investigations (2018)

Allele T

OR 1.20

p 1.0e-3

N 9,679

Meta-analysis

European

Weber F et al. “IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations.” Genes and Immunity (2008)

Allele T

OR —

p —

Candidate gene study

European

Zhou W et al. “Meta-analysis of the Selected Genetic Variants in Immune-Related Genes and Multiple Sclerosis Risk.” Molecular Neurobiology (2024)

Allele T

OR —

p —

Meta-analysis

multi-ancestry

Soluble IL-2 receptor alpha levels

rs12722489 is a significant cis-regulatory variant influencing circulating soluble IL-2 receptor alpha (sIL-2RA) levels. In healthy control subjects, the rs12722489 and rs2104286 variants together account for approximately 15–18% of the variance in log-transformed sIL-2RA concentration. This quantitative effect is substantially attenuated in multiple sclerosis patients (explaining only 2–5% of variance), suggesting that disease-related biological alterations in IL-2 signaling partially override genetic predisposition. This functional link provides a plausible mechanism connecting rs12722489 to immune-mediated disease risk.

Maier LM et al. “Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL-2RA on immune responses.” Journal of Immunology (baltimore, Md. : 1950) (2009)

Allele C

OR —

p —

Candidate gene study

European

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GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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Research that mentions this SNP (2)

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Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

AssociationN=7,260Anne Hinks et al.(2009)· Arthritis & Rheumatism

This association study identifies IL2RA/CD25 as a susceptibility locus for juvenile idiopathic arthritis (JIA). SNP rs2104286 showed significant association with JIA in UK cases (n=654, OR 0.76 [95% CI 0.66-0.88], P=0.0002), which was replicated in North American cases (n=747, OR 0.84 [95% CI 0.65-0.99], P=0.05). Meta-analysis confirmed highly significant association (OR 0.76 [95% CI 0.62-0.88], P=4.9×10⁻⁵). A second SNP (rs41295061) showed modest evidence for association. The gene encodes the IL-2 receptor α chain and plays a critical role in regulatory T cell development.

Traits studied:Graves' diseaseJuvenile idiopathic arthritisMultiple sclerosisRheumatoid arthritisType 1 diabetes mellitus

PubMed DOI Metascience Observatory

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Haplotypic analysis of Wellcome Trust Case Control Consortium data

AssociationN=17,179Brian L. Browning et al.(2008)· Human Genetics

Applied multilocus localized haplotype clustering to Wellcome Trust Case Control Consortium data (14,000 cases of 7 common diseases + 3,000 controls) to identify disease-associated loci with stronger evidence than single-marker tests. Identified three highly significant associations: 10p15.1 with type 1 diabetes (p=5.1×10⁻⁹), 12q15 with type 2 diabetes (p=1.9×10⁻⁷), and 15q26.2 with hypertension (p=2.8×10⁻⁸), plus 9p21.3 with type 2 diabetes (p=2.8×10⁻⁸). Stringent genotype quality filtering effectively removed false positives from genotyping artifacts.

Traits studied:Bipolar disorderCoronary artery diseaseCrohn's diseaseHypertensionRheumatoid arthritisType 1 diabetesType 2 diabetes

rs12722489

Key Literature Trait Associations

Multiple Sclerosis Risk

Soluble IL-2 receptor alpha levels

GWAS Catalog Trait Associations (2)

Research that mentions this SNP (2)

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