cDNA cloning and genomic structure of three genes localized to human chromosome band 5q31 encoding potential nuclear proteins

Loss of a whole chromosome 5, or a del(5q), is a recurring abnormality in m alignant myeloid diseases. By cytogenetic and molecular analyses, we deline ated previously a 1- to 1.5-Mb region that is deleted in all patients with a del(Bq). In our efforts to identify a myeloid tumor suppressor gene withi n the commonly deleted segment (CDS), we have cloned and characterized the genes encoding three putative nuclear proteins, each of which contains a bi partite nuclear localization signal (NLS). In addition, C5ORF5 contains a p utative rhoGAP domain at the N-terminus, C5ORF6 has a proline-rich sequence near the N-terminus, and C5ORF7 has a zinc-finger domain that partially ov erlaps the NLS. All three genes are ubiquitously expressed and encode novel proteins. The C5ORF5 cDNA is 5.47 kb encoding a protein of 915 amino acids (aa) with a predicted molecular mass of similar to 105 kDa. C5ORF5 has 23 exons spanning over 27 kb. The C5ORF6 transcript is 4.1 kb encoding a prote in of 392 aa with a predicted molecular mass of similar to 43 kDa. C5ORF6 h as 5 exons and spans similar to 11 kb. The C5ORF7 cDNA is 6.3 kb and encode s a protein of 1417 aa with a predicted molecular mass of similar to 155 kD a. C5ORF7 has 24 exons spanning similar to 64 kb. All three genes were loca lized to the distal half of the CDS between D5S1983 and D5S500. We evaluate d each as a candidate tumor suppressor gene by the analysis of myeloid leuk emia cells from patients with -5/del(5q), but no inactivating mutations wer e identified. (C) 2000 Academic Press.