ZIC3 encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. Clones corresponding to the ZIC3 gene were isolated from a human differentiated teratocarcinoma cDNA library. The deduced 467-residue protein shows 98% amino acid similarity to the mouse protein.Zic3 expression occurred in the primitive streak as early as embryonic day 7.0 and in structures in which malformations occasionally arise among human males with situs ambiguus. All of the Zic proteins contain 5 C2H2 zinc fingers within a domain that shows homology with the Drosophila pair-rule gene, 'odd paired' (opa).