• Gene: CD226 (DNAX Accessory Molecule-1)

• Chromosome: 18q22.3

• Position (GRCh38): Chr18: 67600833

• Location Within Gene: Exon 7 (missense variant)

• T allele

• Causes a Glycine-to-Serine substitution at position 307 (G307S)

• Alters the cytoplasmic tail of the CD226 receptor

• Modifies phosphorylation dynamics, possibly changing downstream signaling behavior

• Impacts how CD226 interacts with other costimulatory or inhibitory receptors (e.g., TIGIT, CD96)

• Affects T-cell and NK cell activation thresholds

• Enhances cytotoxic immune responses

• Alters immune synapse formation

• Reduces balance with competing inhibitory receptors (e.g., TIGIT), tipping toward inflammatio

• European (EUR): T allele ~40–45%

• Asian (EAS): T allele ~20–30%

• African (AFR): T allele ~35%

  (Source: gnomAD, 1000 Genomes)

• CD226, TIGIT, CD96, PVR (ligand)

• Costimulatory/inhibitory receptor balance

• T-cell activation

• NK-mediated cytotoxicity

• Immune checkpoint regulation

• Autoimmune Addison’s Disease

• Type 1 Diabetes

• Multiple Sclerosis

• Rheumatoid Arthritis

• Graves’ Disease

• Systemic Lupus Erythematosus

• rs763361 T allele is consistently associated with higher autoimmune risk in large GWAS cohorts

• Functional studies show altered phosphorylation patterns in the CD226 receptor tail

• Important in Treg/effector cell balance and autoimmune cytotoxicity targeting

• Contributes to heightened immune aggression in genetically susceptible individuals

• Relevant in conditions involving organ-specific targeting, such as adrenal cortex destruction in Addison’s

• Emerging as a target for immunomodulation research, especially in balancing CD226/TIGIT signaling axis

• Contributes to heightened immune aggression in genetically susceptible individuals

• Relevant in conditions involving organ-specific targeting, such as adrenal cortex destruction in Addison’s

• Emerging as a target for immunomodulation research, especially in balancing CD226/TIGIT signaling axis

rs763361 (G307S) in CD226 is a missense variant that tips the balance of immune costimulation toward overactivation. Its strong link to Addison’s and other autoimmune conditions makes it a valuable marker for immune profiling and risk prediction.

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