CCDC73

CCDC73 is a component of the inner dynein arm f (IDAf) complex in motile cilia, where it associates with DNAH10, CFAP57, and DYNLL1 and is required for proper IDAf complex assembly (PMID:40898283). Loss of DNAH10 reduces CCDC73 levels alongside CFAP57 and DYNLL1, placing CCDC73 within an interdependent IDAf assembly module (PMID:40898283). Despite this ciliary role and its conservation, individual knockout of Ccdc73 in mice is dispensable for spermatogenesis and male fertility under laboratory conditions (PMID:29563520). Beyond these observations, no further mechanistic detail—including molecular activity or direct structural role within the dynein arm—has been characterized in the available corpus.

1. 2018 Medium

   To test whether CCDC73 is required for male reproduction, its loss-of-function consequence in vivo was needed; the result established that single-gene loss is dispensable for fertility.

   Evidence CRISPR/Cas9 Ccdc73 knockout mouse with testis weight, sperm count, and histology readouts

   PMID:29563520

   Open questions at the time

   • Does not address function in non-reproductive ciliated tissues
   • Possible functional redundancy with paralogs not tested
   • No molecular or biochemical role assigned
2. 2025 Medium

   To define CCDC73's molecular context, its protein partners and assembly role were determined, establishing it as an IDAf complex component dependent on DNAH10.

   Evidence Co-IP, immunostaining, proteomics, and Dnah10 knockout mouse with expression readouts

   PMID:40898283

   Open questions at the time

   • Direct binding partner versus indirect complex member not fully resolved
   • No molecular/enzymatic activity assigned to CCDC73
   • Ciliary motility phenotype of CCDC73 loss not measured

• The molecular function of CCDC73 within the IDAf complex and the physiological consequence of its loss in motile-cilia-dependent processes remain undefined.
• No structural model of CCDC73 within the dynein arm
• No measurement of ciliary beat or axonemal defects upon CCDC73 loss
• Mechanism of recruitment into the IDAf complex unknown