We have determined the DNA sequence and genomic organization of D12S53E (Pmel 17), the human homologue of the mouse silver (si) locus. D12S53E encodes a melanosomal matrix protein whose expression is closely correlated with cellular melanin content and which is a frequent melanoma tumor antigen recognized by cytotoxic T lymphocytes. D12S53E is a likely candidate gene for some cases of human oculocutaneous albinism not associated with known albinism loci.