Cfap46-KO Mouse

CFAP46, or Cilia and Flagella Associated Protein 46, is involved in ciliary function, specifically as a component of the C1d projection of the ciliary central apparatus. Mucociliary clearance, which is crucial for the innate defense mechanism of the respiratory system against inhaled pathogens, depends on the rhythmic movement of epithelial cilia where CFAP46 plays a part [1,2].

Pathogenic variants in CFAP46 have been identified as a cause of primary ciliary dyskinesia, a rare genetic disorder leading to chronic airway infections due to insufficient mucociliary clearance. C1d-defective primary ciliary dyskinesia associated with CFAP46 pathogenic variants shows normal situs composition, nasal nitric oxide production rates, ciliary ultrastructure, and ciliary beating, but affected individuals still exhibit insufficient ciliary clearance [1]. In phylogenetically distant birds, the concurrent loss of CFAP46 and WDR93, another ciliary gene, has been observed, suggesting potential implications in host-pathogen interactions [2]. Additionally, in hepatocellular carcinoma, a novel fusion transcript VTI1A-CFAP46 was discovered, with the link to autophagy in HCC patients worthy of further investigation [3].

In conclusion, CFAP46 is essential for ciliary function and its disruption can lead to primary ciliary dyskinesia. The discovery of the gene's involvement in various biological scenarios such as in host-pathogen interactions in birds and in a novel fusion transcript in hepatocellular carcinoma provides new insights into its biological functions and potential disease associations.

References:

1. Wohlgemuth, Kai, Hoersting, Niklas, Koenig, Julia, Dworniczak, Bernd, Omran, Heymut. 2024. Pathogenic variants in CFAP46, CFAP54, CFAP74 and CFAP221 cause primary ciliary dyskinesia with a defective C1d projection of the central apparatus. In The European respiratory journal, 64, . doi:10.1183/13993003.00790-2024. https://pubmed.ncbi.nlm.nih.gov/39362668/

2. Salve, Buddhabhushan Girish, Kurian, Amia Miriam, Vijay, Nagarjun. 2023. Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds. In Royal Society open science, 10, 230801. doi:10.1098/rsos.230801. https://pubmed.ncbi.nlm.nih.gov/37621660/

3. Tsuge, Shunichi, Saberi, Behnam, Cheng, Yulan, Gurakar, Ahmet, Meltzer, Stephen J. 2019. Detection of Novel Fusion Transcript VTI1A-CFAP46 in Hepatocellular Carcinoma. In Gastrointestinal tumors, 6, 11-27. doi:10.1159/000496795. https://pubmed.ncbi.nlm.nih.gov/31602373/