ZIC2

ZIC2 is a gene in humans that encodes Zic family member 2, a transcription factor characterized by multiple C2H2 zinc finger domains. It is part of the ZIC gene family, which plays essential roles in embryonic development and central nervous system formation. The gene is conserved across vertebrates and is expressed in the developing neural tube and forebrain.

The ZIC2 protein is a nuclear transcription factor that binds DNA and regulates the expression of genes involved in neural development. It contains five C2H2-type zinc finger motifs, a characteristic feature of ZIC family proteins that enables DNA interaction. ZIC2 participates in processes such as neural tube closure, forebrain patterning, and the formation of midline structures; in model organisms, disruptions of Zic2 can lead to impaired forebrain development and midline differentiation.

Clinically, pathogenic variants in ZIC2 are associated with holoprosencephaly spectrum disorders, ranging from severe holoprosencephaly to milder forebrain defects, often with facial anomalies. ZIC2 haploinsufficiency contributes to these malformations, and ZIC2 sequencing is considered in genetic evaluations of unexplained forebrain anomalies.

Research in mouse and other vertebrate models underscores the conserved role of ZIC2 in neural development and midline formation. The gene's activity may intersect with signaling pathways involved in developmental patterning, and zebrafish and other systems have provided additional insight into its regulatory networks.