DCX gene

The DCX gene (SCG stands for:doublecortin) is a protein-coding gene located on chromosome Xq23. The DCX gene encodes a member of the doublecortin family. This doublecortin protein is a cytoplasmic protein and contains two doublecortin domains that bind microtubules. Several transcript variants encoding different isoforms have been found for this gene. An important paralog of this gene is MAPKAPK2.

In the developing cerebral cortex, cortical neurons must migrate long distances to reach the site of their final differentiation. The encoded protein appears to control neuronal migration by regulating microtubule organization and stability. In addition, the encoded protein interacts with LIS1, the regulatory gamma subunit of platelet-activating factor acetylhydrolase. This interaction is important for the proper function of microtubules in the developing cortex. Mutations in this gene cause abnormal migration of neurons during development and disrupt the layering of the cortex, leading to epilepsy, cognitive impairment, subcortical band heterotopia ("double cortex" syndrome) in females and lissencephaly in males.

Diseases associated with DCX include:

• Lissencephaly, X-linked, 1 and
• Band heterotopia (Band heterotopia, also known as double cortex syndrome, is a form of diffuse gray matter heterotopia that almost exclusively affects females. Refractory epilepsy is present in almost all affected patients, with focal epilepsy being the most common phenotype).

1. Mauffrey P et al. (2019) Progenitors from the central nervous system drive neurogenesis in cancer. Nature 569:672-678.
2. Wang W et al. (2024) DCX knockout ferret reveals a neurogenic mechanism in cortical development. Cell Rep 43:114508.