• Gene: MICA (MHC Class I Polypeptide–Related Sequence A)

• Chromosome: 6p21.33

• Position (GRCh38): Chr6: 31324726

• Location Within Gene: Exon 3 (missense variant)

• G allele
  Results in a Valine to Methionine substitution at position 129 (Val129Met)

• Affects the binding affinity of MICA to NKG2D, a key receptor on NK and CD8+ T cells

• The G (Val) allele is linked to stronger binding, leading to increased immune activation

• Also impacts cell-surface stability and shedding of soluble MICA, which modulates immune surveillance

• MICA is a stress-inducible ligand that signals immune activation in infected or damaged cells

• Stronger interaction with NKG2D promotes innate immune activation and cytotoxicity
  Plays a dual role in tissue protection and immune-triggered autoimmunity
  
  

• European (EUR): G allele ~30–40%

• East Asian (EAS): G allele ~60–70%

• African (AFR): G allele ~25–35%
  (Source: gnomAD, HapMap)

• MICA, NKG2D (KLRK1), HLA Class I

• Stress-induced immune surveillance

• NK cell– and CD8+ T cell–mediated cytotoxicity

• MHC-related immune modulation

• Autoimmune Addison’s Disease

• Type 1 Diabetes

• Celiac Disease

• Rheumatoid Arthritis

• Psoriasis

• Autoimmune Thyroid Disease

• Vitiligo

• rs1051794 has been associated with MICA-NKG2D hyperactivity in autoimmune conditions

• Val129 variant shows increased binding affinity and potentiated immune signaling

• Strong link to organ-specific autoimmune attack, especially adrenal cortex and gut epithelium

• G allele carriers may have overactive immune surveillance, especially in tissues under stress

• Elevates risk of targeted tissue destruction in autoimmune contexts

• May influence immune checkpoint modulation 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

rs1051794 in MICA encodes a high-affinity variant that intensifies immune cell activation via the NKG2D pathway. It contributes to Addison’s and other autoimmune diseases by lowering the threshold for cytotoxic attack on self-tissues.

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