Abstract. Utilizing a eDNA clone encoding the oligodendrocyte-myelin glycoprotein (OMgp) to screen a human genomic DNA library, we have obtained a clone that contains the OMgp gene. The genornic clone was restriction mapped and the OMgp gene and its 5' and 3' flanking regions were sequenced. A single intron is found in the 5' untranslated region of the gene, while the coding region is uninterrupted by an intron. This placement of a single intron in the OMgp gene is identical to that of the gene for the o~-chain of platelet glycoprotein Ib, which, along with OMgp, belongs to a family of proteins sharing two distinct structural domains: an NH2-terminal cysteine-rich domain and an adjacent domain of tandem leucine-rich repeats. Hence, it is possible that this family of proteins is not only related in terms of primary structure, but also through similar gene structure. Sequence comparison of the 5' and 3' flanking regions did not reveal striking similarities to other DNA sequences, and no obvious promoter elements were noted. By hybridization of the genomic clone to metaphase cells, we have localized the human OMgp gene to chromosome 17 bands qll-12, a region to which the neurofibromatosis type 1 gene has been previously mapped.T HE oligodendrocyte-myelin glycoprotein (OMgp) ~ is a highly glycosylated protein of oligodendrocytes and central nervous system myelin which appears to be localized at the paranodal region of the myelin sheath (Mikol and Stefansson, 1988). OMgp is anchored in the plasma membrane as a 120-kD glycoslyphosphatidylinositol-linked form that can be released from the membrane upon incubation with phospholipase C to generate a soluble 105-kD polypeptide. Based on eDNA sequence, the predicted primary structure of OMgp consists of four domains (Mikol et al., 1990). At the NH2-terminus there is a 32-amino acid cysteine-rich (CR) motif. This is followed by a domain consisting of 7 I/2 tandem leucine-rich repeats (LRs) of 24 amino acids each, and a domain of 4 1/2 repeats of 40 residues each that are rich in serines and threonines. A hydrophobic COOH-terminal segment is most likely cleaved concomitant with the attachment of a phosphatidylinositolcontaining glycan (Cross, 1990).