CC2D1A

Cilia effects upon perturbation of CC2D1A

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Decrease

Ciliogenesis screen results (2 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Human ciliopathy phenotype:

Intellectual disability, cardiac heterotaxy, cystic kidneys, abnormal CSF circulation

Ciliopathy associations

• Renal dysplasia (heterotaxy spectrum)
• Visceral Heterotaxy / Situs Inversus

Subcellular localization

cilia, nucleus

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• T cell biology

Function

CC2D1A has localized in cilia. Western blot analysis of fibroblast cell line lysates shows elimination of detectable CC2D1A expression in the two patient fibroblasts compared with the control fibroblasts and the father’s fibroblasts (Fig 5A). To analyze the cilia in fibroblasts, we immunostained for acetylated tubulin to show cilia and phalloidin to show the cytoskeleton. Under normal conditions, control fibroblasts showed a monocilium with an average length of 3.50 ± 1.15 μm (n = 590). In our index patients, either there were fewer ciliated cells (Fig 5B) or the ciliary length was significantly diminished (Fig 5C–F) (DOI: 10.26508/lsa.202402708). Xenopus: cc2d1a expressed in LRO, epidermis, pronephric duct, nephrostomes, and brain ventricular zone. Loss causes cardiac heterotaxy, cystic kidneys, and abnormal CSF circulation via defective ciliogenesis. Patient fibroblasts: defective ciliogenesis confirmed. Human: 4 patients with biallelic variants showing intellectual disability, cardiac heterotaxy, cystic kidneys, abnormal CSF (PMID:39168639).

Model organism evidence