Coiled-coil and C2 domain-containing protein 2A (CC2D2A)

Coiled-coil and C2 domain-containing protein 2A (CC2D2A) is a structural protein required for the formation and function of primary cilia, encoded by the *CC2D2A* gene located on chromosome 4p15.32. It contains a coiled-coil region as well as a C2 domain that is likely involved in calcium-dependent membrane targeting[7]. CC2D2A localizes to the transition zone at the base of primary cilia and is essential for the assembly of ciliary subdistal appendages and the establishment of a barrier between the ciliary membrane and the general cell membrane[2][4]. Functional loss of CC2D2A disrupts ciliogenesis and impairs Sonic Hedgehog signaling, leading to developmental defects typically seen in the ciliopathies Meckel syndrome (type 6) and Joubert syndrome (type 9)[5][1][4]. Disease-causing variants in this gene display genotype-phenotype correlation: null alleles are associated with the lethal Meckel syndrome, while missense/hypomorphic variants more often result in Joubert syndrome, which is compatible with life[5][4][7]. The protein may also interact with CEP290, another critical ciliary protein, within multiprotein complexes that regulate ciliary membrane composition and signaling[2][7][5]. There are currently no known drugs that directly target CC2D2A, and its clinical significance is as a diagnostic or prognostic marker in relevant syndromes rather than a therapeutic target.

Other names

JBTS9MKS6KIAA1345COACH2RP93Meckel syndrome, type 6Joubert syndrome 9