RP58, a sequence-specific transcriptional repressor sharing homology with the POZ domain of a number of zinc-finger proteins, is highly synthesized in brain and localized in condensed chromatin regions, suggesting a role in transcriptional repression in the central nervous system. In the present study, genomic clones of the human rp58 gene were isolated to determine the complete genomic organization. Sequence analyses indicated that the human rp58 gene encoding the functional protein is uninterrupted over its entire 4.2 kb length. Comparison of the human and mouse rp58 genes revealed that they share not only a high homology in the amino acid sequences of their encoded proteins, but also a high degree of structural similarity at the genomic level. RT-PCR analysis also demonstrated the existence of an alternatively spliced form of rp58 similar to the previously reported zinc-finger cDNA, C2H2-171. Chromosomal mapping by fluorescence in situ hybridization analysis allowed localization of the rp58 gene to human chromosome 1q44 ter, a genetic region associated with a number of human malignancies and neurological disorders.