Capicua (protein)

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Capicua is a human protein produced from the CIC gene. It acts mainly as a transcriptional repressor, helping control which genes are turned on or off. Capicua binds DNA using two conserved domains (HMG-box and C1) and has a signal that lets it enter the cell nucleus. There are two forms of Capicua, called CIC-S (short) and CIC-L (long), which differ at the N-terminal end.

Capicua is highly conserved across species, including fruit flies, where it was first studied. The name Capicua comes from the Catalan phrase for "head and tail."

In the brain, Capicua forms a complex with ataxin 1 (the CIC-ATXN1 complex). This complex helps keep normal cell function, but when ataxin 1 is mutated, the altered complex can damage cerebellar cells. In mouse models, blocking this complex can reduce symptoms.

Capicua also acts as a tumor suppressor in many cancers. Mutations in CIC have been found in oligodendroglioma, a type of brain tumor, and a fusion between CIC and DUX4 (CIC-DUX4) can drive an aggressive Ewing-like sarcoma by activating genes.

A rare, autosomal dominant intellectual developmental disorder called ADDI 45 has been linked to CIC mutations (first described in 2017).

Some research suggests CIC mutations may contribute to cerebral folate deficiency as well (reported in 2021).

Overall, Capicua is a conserved transcriptional repressor with important roles in development, brain function, and cancer.