A clone from a lambda gt11 cDNA expression library of HeLa cells was isolated, sequenced, and shown to encode a new human zinc finger protein. The cDNA of the gene termed ZFP161 has an open reading frame of 1347 bp. The predicted protein comprises 449 amino acid residues and contains five zinc finger motifs of the Krüppel type near the C-terminus and a BTB/POZ domain in the N-terminal region. The protein is 98% homologous to a murine zinc finger protein, ZF5 (M. Numoto et al., 1993, Nucleic Acids Res. 21: 3767-3775), which is a putative transcriptional repressor of c-myc and exhibits growth-suppressive activity in mouse cell lines. Through the use of a panel of somatic cell hybrids for chromosomal assignment and DNAs of somatic cell hybrids containing a deleted chromosome 18 for fine mapping, the human gene ZFP161 was localized to 18p11.21-pter. Therefore, ZFP161 is a candidate gene by position for the holoprosencephaly type 4 gene, HPE4, which is involved in congenital malformations. With DNAs from an interspecific backcross, two homologous mouse genes, Zfp161 and Zfp161-rs1, were mapped to chromosome 17 and the X chromosome, respectively. Mapping of Zfp161 confirms and extends a region of homology between distal mouse chromosome 17 and human 18p.