Coiled-coil domain-containing protein 88C (CCDC88C)

Coiled-coil domain-containing protein 88C (CCDC88C, commonly known as Daple) is a **cytosolic scaffold protein** encoded by the human CCDC88C gene and distinguished by its interaction with Dishevelled proteins and Frizzled receptors in the Wnt signaling pathway[1][6]. CCDC88C contains specialized motifs—including a PDZ-domain binding motif and a G-protein binding and activating (GBA) motif—that enable complex regulation of both canonical and non-canonical Wnt signaling. It acts as a **non-receptor guanine nucleotide exchange modulator (GEM)** by directly activating Gαi subunits upon Wnt receptor stimulation, thereby influencing key cellular processes such as proliferation, migration, invasion, apical constriction, and EMT[3][6]. Mutations in CCDC88C cause **congenital hydrocephalus** and **spinocerebellar ataxia 40**; the gene’s expression levels and isoform balance are prognostic in several cancer types, especially in metastatic melanoma and colorectal cancer, where it can serve both as a tumor suppressor and a driver of metastatic progression depending on isoform expression and cellular context[3][5][6].

Other names

DapleKIAA1509HKRP2SCA40HYC1Dishevelled-associating protein with a high frequency of leucine residuesHook-related protein 2Spinocerebellar ataxia 40

Modulation of Wnt signaling via interaction with Frizzled receptors and G-proteins (Gi alpha); inhibits canonical pathway and activates non-canonical pathway leading to diverse cellular responses (see above functions)[3][5][6]. Guanine nucleotide exchange modulation on heterotrimeric G-proteins. Influences cell behavior by regulating EMT and cell invasion