We have identified a novel factor H-related cDNA, which was isolated from a human liver cDNA library. The DOWN16 clone is 1269 base pairs in size and hybridized to a mRNA of 1.4 kilobases. Similar to the previously described factor H-related proteins, the predicted translation product of 331 amino acids contains a hydrophobic signal sequence followed by a stretch of five short consensus repeats (SCRs). These five SCRs display homology to SCRs of factor H: SCRs1-3 (DOWN16) are homologous to SCRs6-8 of factor H, while SCRs4 and -5 are related to SCRs19 and -20. In vitro translation demonstrated that the DOWN16 cDNA encodes a primary translation product of an apparent molecular mass of 37,500 Da which is directed to the secretory pathway and is glycosylated. Thus, we propose that the protein will be present in human serum. The relatedness of structural elements between this novel gene and factor H may suggest common functions of these proteins not yet determined.