EFCAB10

EFCAB10 is a radial spoke protein of motile cilia that maintains ciliary motility by anchoring the adenylate kinase AK8 to the radial spoke (PMID:41055978). It physically interacts with both AK8 and the radial spoke component RSPH3B, contributing to the structural integrity of the radial spoke complex (PMID:41055978). The dependency is unidirectional: loss of EFCAB10 completely abolishes ciliary AK8, whereas loss of AK8 does not affect EFCAB10 localization, establishing EFCAB10 as the anchoring partner rather than the cargo (PMID:41055978). Consistent with this role, Efcab10 knockout mice display disrupted ciliary motility and primary ciliary dyskinesia-related phenotypes including respiratory defects and infertility (PMID:41055978). Beyond its radial spoke anchoring function defined in these mouse studies, no further mechanistic detail has been characterized in the available corpus.

1. 2025 High

   Whether EFCAB10 had a defined role in cilia was unknown; knockout mouse studies established it as a radial spoke protein that anchors AK8 and is required for motile cilia function, defining a directional anchoring relationship.

   Evidence Efcab10 and Ak8 knockout mouse models with ciliary localization analysis showing complete loss of ciliary AK8 upon EFCAB10 loss but no reciprocal effect

   PMID:41055978

   Open questions at the time

   • Molecular basis of how EFCAB10 tethers AK8 to the spoke is undefined
   • No structural model of the EFCAB10-AK8-RSPH3B assembly
   • Functional consequence of AK8 loss on local nucleotide handling within cilia not established
2. 2025 Medium

   How EFCAB10 integrates into the radial spoke was unclear; biochemical interaction with RSPH3B placed it physically within the radial spoke complex.

   Evidence Co-immunoprecipitation/pulldown in mouse cilia demonstrating EFCAB10-RSPH3B interaction

   PMID:41055978

   Open questions at the time

   • Interaction reported from a single lab without reconstitution or structural validation
   • Stoichiometry and binding interface within the radial spoke unknown
   • Whether RSPH3B binding is required for AK8 anchoring not dissected
3. 2025 High

   The physiological importance of EFCAB10 was untested; knockout mice linked its loss to ciliary motility defects and PCD-like disease phenotypes.

   Evidence Efcab10 knockout mouse with ciliary motility measurements and phenotypic analysis of respiratory defects and infertility

   PMID:41055978

   Open questions at the time

   • No human PCD patients with EFCAB10 mutations reported in the corpus
   • Mechanistic link between AK8 mislocalization and motility failure not directly demonstrated

• Whether EFCAB10 mutations cause primary ciliary dyskinesia in humans, and the structural mechanism by which it tethers AK8 to the radial spoke, remain unresolved.
• No human genetic evidence in the corpus
• No high-resolution structure of the anchoring complex
• Role of EFCAB10 EF-hand/calcium binding in function untested