CFAP119

Cilia effects upon perturbation of CFAP119

Loss-of-function effect:

Short, coiled or absent sperm flagella with missing central pair and disorganized microtubule doublets (mouse knockout)

Phenotypes

Mouse phenotype:

decreased vertical activity, decreased locomotor activity, increased circulating hdl cholesterol level, increased circulating cholesterol level

Subcellular localization

flagella, axoneme, acrosome

References: PMID:25613900, doi:10.1093/biolre/ioae112, PMID:37601242

Functional category

• Ciliary assembly/disassembly
• Reproduction & sperm

Function

CFAP119 (CCDC189) is a sperm flagellar protein. Immunoelectron microscopy places it at the radial spoke of the first peripheral microtubule doublet of the sperm axoneme, where it interacts with CABCOCO1, the radial spoke protein RSPH1 and the IFT proteins IFT20 and IFT88. Ccdc189-knockout male mice are infertile, with fewer and poorly motile sperm, most of which have short, coiled or curved flagella and abnormal heads; mutant spermatids have a longer manchette and diffuse IFT88 (Wang et al., 2023, Natl Sci Rev, PMID 37601242). In an independent knockout, antibody staining shows CCDC189 in spermatocytes and round and elongating spermatids and in the acrosome and flagellum of mouse sperm. Loss of Ccdc189 causes oligo-astheno-teratozoospermia: sperm flagella have disorganized or missing peripheral microtubule doublets and outer dense fibers, the central pair is consistently absent, the end piece often lacks an axoneme, and the connecting piece and mitochondrial sheath are disorganized. CCDC189 binds the poly(A)-binding proteins PABPC1 and PABPC2, and IFT20 protein, but not Ift20 mRNA, is increased in knockout testes, suggesting a role in translational control during spermiogenesis (Zhou et al., 2024, Biol Reprod 111(4):800-814, doi 10.1093/biolre/ioae112). A splice donor variant in bovine CCDC189 is associated with asthenospermia (Iso-Touru et al., 2019, BMC Genomics, PMID 30975085).