Hypothetical model of the human leucocyte antigen (HLA)-H protein based upon its homology with major histocompatibility complex (MHC) class I molecules. The HLA-H protein is a single polypeptide with three extracellular domains, which would be analogous to the α1, α2 and α3 domains of other MHC class I proteins. In contrast to other members of the MHC class I family, the α1 and α2 domains in the HLA-H protein are nonpolymorphic. _b2-microglobulin is a separate protein and interacts with the HLA-gene product in a noncovalent manner in the α3 homologous region. In addition, the protein contains a membrane-spanning region and a short cytoplasmic tail. The approximate locations of Cys282Tyr and His63Asp are indicated. (With permission from Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, et al. A novel MHC class-I like gene is mutated in patients with hereditary haemochromatosis. Nat Genet, 1996; 13: 399–408. (4))