Following immunoscreening, we have cloned and sequenced a human cDNA encoding a novel member of the expanding helicase family. The deduced protein, designated hZFH (human zinc-finger helicase), contains the seven domains conserved among the helicase superfamily II and four potential zinc-fingers motifs. In particular, hZFH shows significant similarity to some proteins of the Snf2-like family, known to act as transcriptional regulators for multiples genes. Furthermore, hZFH has 68.5% identity to a human Mi-2 autoantigen to which autoantibodies are produced by a subgroup of patients affected by dermatomyositis. Northern-blot analyses have revealed several hZFH mRNAs with quantitative differences in various human tissues. One alternative splice site of hZFH mRNA was demonstrated and others were predicted. We also report the chromosomal localization of gene hZFH to locus 17p13-17p12 by in situ hybridization. Thus, this novel gene appears as a candidate for several malignant and genetic diseases associated with this region of the genome. The combination of these features suggests that hZFH plays an important role in gene regulation.