MICA Gene - Structure, Function, and Clinical Significance | NCBI, UniProt, OMIM

MICA encodes a highly polymorphic MHC class I-like molecule that functions as a stress-induced ligand for the NKG2D receptor on natural killer (NK) cells, CD8+ T cells, and γδ T cells. Unlike classical MHC class I molecules, MICA does not bind β2-microglobulin or present peptides. Its expression is upregulated in response to cellular stress, infection, and malignant transformation, enabling immune recognition and elimination of stressed or transformed cells. Polymorphisms in MICA are associated with susceptibility to autoimmune diseases, viral infections, and cancer, and influence outcomes in hematopoietic stem cell transplantation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• NKG2D signaling in NK cells (Reactome: R-HSA-199168)

• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome: R-HSA-198933)

• Class I MHC mediated antigen processing & presentation (Reactome: R-HSA-983169)

MICA is a transmembrane glycoprotein of 383 amino acids (UniProt Q29983) with three extracellular domains (α1, α2, α3), a transmembrane region, and a cytoplasmic tail. It is structurally similar to MHC class I molecules but does not bind β2-microglobulin or present antigens. MICA is expressed at low levels on the surface of normal cells but is upregulated under stress conditions (e.g., heat shock, viral infection, DNA damage). It binds the NKG2D receptor, activating NK cells and T cells to eliminate stressed or malignant cells. The protein is highly polymorphic, with over 100 alleles, and can be shed from the cell surface by ADAM proteases, generating soluble MICA that inhibits NKG2D signaling and promotes immune evasion in cancer.