We have recently characterized a novel mammalian gene family, encoding membrane glycoproteins with four trans-membrane domains. This gene family includes the previously studied PMP22, which is involved in the Charcot-Marie-Tooth neuropathy, and three novel genes: TMP, XMP, and YMP (HGMW-approved symbols EMP1, EMP2 and EMP3, respectively). The Tmp (tumor-associated membrane protein) gene was isolated from a c-myc induced mouse brain tumor and is expressed in several highly proliferative cell types. We have now isolated cDNAs of the mouse Xmp and Ymp genes and determined the chromosomal localization of mouse Tmp, Xmp, and Ymp. Tmp was mapped to mouse chromosome 6, Xmp was mapped to chromosome 16, and Ymp was mapped to chromosome 7. Tmp and Ymp map to paralogous chromosomal regions, whereas Xmp maps to a chromosomal region that is putatively paralogous to a region on chromosome 11, to which Pmp22 was previously mapped. These data suggest that this family of membrane glycoproteins evolved as a result of chromosomal duplications.