HLA-DRA Gene - Structure, Function, and Clinical Significance

HLA-DRA encodes the alpha chain of the HLA-DR heterodimer, a cell surface glycoprotein belonging to the MHC class II family. This molecule is essential for presenting exogenous peptide antigens to CD4+ T helper cells, thereby initiating and regulating adaptive immune responses. The alpha chain is invariant, while the beta chain (encoded by HLA-DRB1) provides polymorphism. HLA-DRA is constitutively expressed on antigen-presenting cells such as dendritic cells, macrophages, and B cells, and can be induced by interferon-gamma on other cell types.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Antigen processing and presentation (KEGG hsa04612)

• Phagosome (KEGG hsa04145)

• Th1 and Th2 cell differentiation (KEGG hsa04658)

• Th17 cell differentiation (KEGG hsa04659)

• Intestinal immune network for IgA production (KEGG hsa04672)

The HLA-DRA protein (UniProt P01903) is a 254-amino-acid type I transmembrane glycoprotein. It forms a heterodimer with HLA-DRB to create the functional HLA-DR molecule. The alpha chain consists of two extracellular domains (α1 and α2), a transmembrane region, and a short cytoplasmic tail. The α1 domain contributes to the peptide-binding groove, while the α2 domain contains a conserved N-glycosylation site. The protein is essential for loading antigenic peptides onto MHC class II molecules in endosomal compartments, facilitated by the chaperone invariant chain (CD74) and HLA-DM.