CFAP410, also known as C21orf2, is a protein-coding gene. It localizes at the basal body of cilia/flagella and plays essential roles in ciliogenesis, neuronal development, and DNA damage repair [3,4]. Cilia are important organelles, and defects in ciliary structure or function can lead to ciliopathies, highlighting the biological importance of CFAP410.

In terms of disease associations, variants in CFAP410 have been found to cause retinal dystrophy, including cone-rod dystrophy and retinitis pigmentosa (RP), often with features like posterior staphyloma and double hyperautofluorescence rings [1]. Pathogenic missense variants in CFAP410 can cause cone-rod dystrophy with macular staphyloma, and the pathogenic mechanisms may be related to alterations in protein stability and degradation through the ubiquitin-proteasome pathway [2]. A homozygous in-frame duplication in CFAP410 has been associated with cone-rod dystrophy, macular staphyloma, and short stature [5]. Also, coding and non-coding variants in CFAP410 are linked to early-onset non-syndromic retinal degeneration [6].

In conclusion, CFAP410 is crucial for ciliogenesis and other cellular processes. Its dysfunction, as seen in various disease-associated variants, is mainly related to retinal dystrophies. Understanding CFAP410's role through these disease-related findings helps in uncovering the mechanisms of ciliopathies, especially those related to the retina, providing potential insights for future treatment strategies.

References:

1. Li, Xueqing, Wang, Yingwei, Wang, Junwen, Wang, Panfeng, Zhang, Qingjiong. . Double Hyperautofluorescence Rings as a Sign of CFAP410-related Retinopathy. In Investigative ophthalmology & visual science, 64, 44. doi:10.1167/iovs.64.15.44. https://pubmed.ncbi.nlm.nih.gov/38153748/

2. Yang, Shaoqing, Li, Ya, Yang, Lin, You, Ya, Lei, Bo. 2023. Pathogenicity and functional analysis of CFAP410 mutations causing cone-rod dystrophy with macular staphyloma. In Frontiers in medicine, 10, 1216427. doi:10.3389/fmed.2023.1216427. https://pubmed.ncbi.nlm.nih.gov/37901396/

3. Stadler, Alexander, De Liz, Laryssa V, Gabriel, Heloisa B, Sunter, Jack D, Dong, Gang. 2024. The C-terminus of CFAP410 forms a tetrameric helical bundle that is essential for its localization to the basal body. In Open biology, 14, 240128. doi:10.1098/rsob.240128. https://pubmed.ncbi.nlm.nih.gov/39255848/

4. Stadler, Alexander, Gabriel, Heloisa B, De Liz, Laryssa V, Sunter, Jack D, Dong, Gang. 2025. CFAP410 has a bimodular architecture with a conserved surface patch on its N-terminal leucine-rich repeat motif for binding interaction partners. In Frontiers in cell and developmental biology, 13, 1507470. doi:10.3389/fcell.2025.1507470. https://pubmed.ncbi.nlm.nih.gov/40018707/

5. Chiu, Ning, Lee, Winston, Liu, Pei-Kang, Tsai, Shawn H, Wang, Nan-Kai. 2021. A homozygous in-frame duplication within the LRRCT consensus sequence of CFAP410 causes cone-rod dystrophy, macular staphyloma and short stature. In Ophthalmic genetics, 43, 378-384. doi:10.1080/13816810.2021.2010773. https://pubmed.ncbi.nlm.nih.gov/34915818/

6. Sangermano, Riccardo, Gupta, Priya, Price, Cherrell, Huckfeldt, Rachel M, Bujakowska, Kinga M. 2024. Coding and non-coding variants in the ciliopathy gene CFAP410 cause early-onset non-syndromic retinal degeneration. In Research square, , . doi:10.21203/rs.3.rs-3871956/v1. https://pubmed.ncbi.nlm.nih.gov/38405922/