Cfap58, or cilia and flagella associated protein 58, is a testis-enriched gene. It is crucial for sperm flagellogenesis and may be involved in the intra-manchette transport/intra-flagellar transport pathway. It also has potential connections with the Notch signaling pathway in ciliogenesis [1,3].

Gene knockout mouse models have shown that loss of Cfap58 leads to severe sperm tail defects, abnormal sperm head shaping due to manchette structure impairment, and increased spermatozoa apoptosis. Biochemically, it interacts with IFT88 and CCDC42 and may stabilize other cargo proteins like CCDC42 in relevant transport pathways [1]. In humans, biallelic mutations or loss-of-function variants in CFAP58 are associated with multiple morphological abnormalities of the sperm flagella (MMAF), a severe form of asthenoteratozoospermia, presenting with flagellar axoneme and mitochondrial sheath defects [2,4]. Exome sequencing in patients with severe sperm motility disorders also identified a patient with a pathogenic variant in CFAP58 [5].

In summary, Cfap58 is essential for spermatogenesis. The study of Cfap58 knockout mouse models has provided crucial insights into male infertility caused by MMAF-associated asthenoteratozoospermia, highlighting the gene's significance in sperm development and male reproductive health [1,2,4,5].

References:

1. Wei, Xiaochao, Wang, Xiuge, Yang, Chunhong, Gao, Yundong, Huang, Jinming. 2024. CFAP58 is involved in the sperm head shaping and flagellogenesis of cattle and mice. In Development (Cambridge, England), 151, . doi:10.1242/dev.202608. https://pubmed.ncbi.nlm.nih.gov/38602507/

2. Sha, Yankun, Sha, Yanwei, Liu, Wensheng, Wang, Yifeng, Zhou, Huiliang. 2020. Biallelic mutations of CFAP58 are associated with multiple morphological abnormalities of the sperm flagella. In Clinical genetics, 99, 443-448. doi:10.1111/cge.13898. https://pubmed.ncbi.nlm.nih.gov/33314088/

3. Li, Zheng-Zheng, Zhao, Wen-Long, Wang, Gui-Shuan, Gu, Ni-Hao, Sun, Fei. . The novel testicular enrichment protein Cfap58 is required for Notch-associated ciliogenesis. In Bioscience reports, 40, . doi:10.1042/BSR20192666. https://pubmed.ncbi.nlm.nih.gov/31904090/

4. He, Xiaojin, Liu, Chunyu, Yang, Xiaoyu, Zhang, Feng, Cao, Yunxia. 2020. Bi-allelic Loss-of-function Variants in CFAP58 Cause Flagellar Axoneme and Mitochondrial Sheath Defects and Asthenoteratozoospermia in Humans and Mice. In American journal of human genetics, 107, 514-526. doi:10.1016/j.ajhg.2020.07.010. https://pubmed.ncbi.nlm.nih.gov/32791035/

5. Oud, M S, Houston, B J, Volozonoka, L, Chemes, H E, Sheth, H. . Exome sequencing reveals variants in known and novel candidate genes for severe sperm motility disorders. In Human reproduction (Oxford, England), 36, 2597-2611. doi:10.1093/humrep/deab099. https://pubmed.ncbi.nlm.nih.gov/34089056/