• Gene: HLA-DRB1 (Human Leukocyte Antigen, Class II, DR Beta 1)

• Chromosome: 6p21.32

• Position (GRCh38): Chr6: 32552129

• Location Within Gene: Exon 2 (missense coding region)

• Also acts as a tag SNP for specific HLA-DRB1 haplotypes

• A allele

Causes a Glycine to Valine substitution at position 86 (Gly86Val) in the peptide-binding groove

• Changes the shape and binding properties of the MHC class II antigen-binding cleft

• Alters how self and foreign peptides are presented to CD4+ T cells

• Increases risk of mistaken self-recognition, leading to autoimmune activation

• Influences T-cell receptor engagement and autoantigen presentation

• Specific DRB1 variants tagged by rs1051792 are associated with loss of immune tolerance

• Alters the landscape of central and peripheral tolerance, especially in the thymus

• European (EUR): A allele ~15–20%

• East Asian (EAS): A allele ~5–10%

• African (AFR): A allele ~20–25%
  (Source: gnomAD, 1000 Genomes)

• HLA-DRB1, CD4, CIITA, HLA-DQ/DP

• MHC class II antigen presentation

• T-cell selection and activation

• Adaptive immune specificity

• Autoimmune Addison’s Disease

• Rheumatoid Arthritis

• Multiple Sclerosis

• Type 1 Diabetes

• Hashimoto’s Thyroiditis

• Celiac Disease

• Myasthenia Gravis

• rs1051792 is widely used as a proxy for high-risk HLA-DRB1 alleles, especially **DRB1*03, 04, 15
  
  

• This single SNP can predict antigen-presentation skew that drives autoimmune recognition

• Repeatedly replicated in Addison’s GWAS studies across European and multi-ethnic cohorts

• rs947474 contributes to an aggressive T-cell activation profile

• Helps define individuals with a Th1-biased immune architecture, relevant to organ-targeting autoimmune diseases

• Being explored as a target in immunosuppressive therapies

• A allele carriers may present self-peptides with higher affinity, triggering T-cell–mediated destruction

• Crucial for predictive genetic panels in autoimmune disease susceptibility

• A defining player in HLA-based polygenic risk scores

rs1051792 in HLA-DRB1 tags a high-risk autoimmune haplotype by altering peptide presentation to CD4+ T cells. It represents one of the most powerful common genetic variants in Addison’s Disease and systemic autoimmunity, bridging innate genetics with adaptive dysregulation.

ItemThis SNP report is intended for informational and educational purposes only. It should not be used to diagnose or treat any health condition. All genetic findings must be interpreted by qualified medical professionals in the context of clinical and family history. description