rs1061235

This is a regulatory variant in the HLA-A gene.

Key Literature Trait Associations

Carbamazepine Hypersensitivity

This variant tags HLA-A*31:01, which is associated with carbamazepine-induced hypersensitivity including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). This association is most relevant in European and Japanese populations. CPIC recommends HLA-A*31:01 testing before carbamazepine initiation and considering alternative anticonvulsants for carriers.

McCormack M et al. “HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.” The New England Journal of Medicine 364(12):1134-1143 (2011)

Allele A

OR —

p 1.0e-12

Large GWAS

Carbamazepine Hypersensitivity (HLA-A*31:01 Tag)

rs1061235 is a proxy SNP for HLA-A*31:01, which is associated with carbamazepine-induced hypersensitivity reactions in Europeans (McCormack et al. 2011, NEJM). The A allele tags HLA-A*31:01 with ~100% sensitivity and 84-96% specificity in Europeans. A known 5-16% false positive rate exists due to cross-reactivity with HLA-A*33:03. Performance is reduced in South/West Asian and Native American populations where different HLA haplotype structures predominate.

McCormack M et al. “HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.” The New England Journal of Medicine 364(12):1134-1143 (2011)

Allele A

OR 8.00

p 1.7e-8

Large GWAS

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ClinVar annotation

Risk Factor

1 submitter3 publications

Carbamazepine hypersensitivity

View on ClinVar →

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Research that mentions this SNP (1)

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Risk for myasthenia gravis maps to a ¹⁵¹ Pro→Ala change in TNIP1 and to human leukocyte antigen‐B*08

AssociationN=3,245Peter K. Gregersen et al.(2012)· Annals of Neurology

A two-stage genome-wide association study of 649 early-onset myasthenia gravis patients identified HLA-B*08 as the major genetic risk factor (OR=6.41, p=2.87×10⁻¹¹³) and TNIP1 Pro151Ala (rs2233290, OR=1.92, p=3.4×10⁻⁹) as a novel non-HLA locus. Together with PTPN22 (rs2476601, OR=1.71, p=8.2×10⁻¹⁰), these loci account for 62.9% of population attributable risk, implicating dysregulation of NF-κB signaling pathways in myasthenia gravis pathogenesis.

Traits studied:Autoimmune thyroid diseaseEarly-onset myasthenia gravis (EOMG)PsoriasisRheumatoid arthritisSystemic lupus erythematosusSystemic sclerosisType 1 diabetes