Cibar1, also known as FAM92A and BARMR1/FAM92A1, is a gene encoding a protein with a Bin/Amphiphysin/Rvs (BAR) domain. BAR domain proteins are involved in sensing and sculpting curved lipid membranes, playing key roles in various cellular processes, including ciliogenesis, cell proliferation, and migration [2,4]. Cibar1 is part of a complex with other proteins like Chibby3 (Cby3) and is associated with pathways related to sperm flagellum development and cilia-related functions [1,2].

Gene knockout studies in mice have provided significant insights into Cibar1's functions. Ablation of Cibar1 in mice leads to male fertility defects due to kinked sperm flagella with mispositioned annulus in the principal piece of the sperm flagellum, suggesting its role in sperm flagellum compartmentalization [1]. CiBAR1-KO mice also exhibit ciliopathy phenotypes, such as ∼28% embryonic lethality due to randomized left-right asymmetry, exocrine pancreatic lesions, and impaired glucose tolerance, indicating its critical role in ciliogenesis depending on the tissue and cell type [2]. Additionally, a novel homozygous Cibar1 (FAM92A) variant has been associated with non-syndromic postaxial polydactyly type A9, further confirming its role in limb development and patterning [3].

In conclusion, model-based research, especially using Cibar1 KO mouse models, has revealed that Cibar1 is essential for sperm flagellum development, ciliogenesis in different tissues, and limb development. Its functions are crucial in understanding male fertility, laterality development, pancreatic function, and limb patterning-related diseases.

References:

1. Hoque, Mohammed, Li, Feng-Qian, Weber, William David, Visconti, Pablo E, Takemaru, Ken-Ichi. 2024. The Cby3/ciBAR1 complex positions the annulus along the sperm flagellum during spermiogenesis. In The Journal of cell biology, 223, . doi:10.1083/jcb.202307147. https://pubmed.ncbi.nlm.nih.gov/38197861/

2. Kim, Eunice N, Li, Feng-Qian, Takemaru, Ken-Ichi. 2024. ciBAR1 loss in mice causes laterality defects, pancreatic degeneration, and altered glucose tolerance. In Life science alliance, 8, . doi:10.26508/lsa.202402916. https://pubmed.ncbi.nlm.nih.gov/39622622/

3. Umair, Muhammad, Ahmed, Zaheer, Shaker, Bilal, Jawad Khan, Muhammad, Alfadhel, Majid. 2024. A novel homozygous FAM92A gene (CIBAR1) variant further confirms its association with non-syndromic postaxial polydactyly type A9 (PAPA9). In Clinical genetics, 106, 488-493. doi:10.1111/cge.14572. https://pubmed.ncbi.nlm.nih.gov/38853702/

4. Zhi Ruan, Xu, Rong Guo, Xin, Bin Wang, Xuan, Yun Ji, Fu. 2020. BARMR1/FAM92A1, a novel gene encoding BAR domain protein with multi-functions. In Gene, 765, 145074. doi:10.1016/j.gene.2020.145074. https://pubmed.ncbi.nlm.nih.gov/32891772/