CFAP57

CFAP57 (cilia- and flagella-associated protein 57; also known as WDR65) is a conserved axonemal protein of motile cilia and sperm flagella, with an N-terminal WD40-repeat beta-propeller region and a long C-terminal coiled-coil region. In Chlamydomonas the ortholog FAP57 (IDA8/BOP2) forms an extended structure along the doublet microtubule that interconnects inner dynein arms with regulatory complexes, including the I1 dynein and the nexin-dynein regulatory complex region, and targets or stabilizes the binding of a subset of single-headed inner dynein arms (notably dyneins g and d) at their sites in the 96-nm axonemal repeat. Orthologs occur only in organisms that assemble inner dynein arms. In human airway epithelium CFAP57 is distributed along the ciliary axoneme, and loss of axonemal CFAP57 reduces ciliary beat frequency and alters waveform. A long isoform is required in sperm: biallelic loss-of-function variants cause spermatogenic failure 95, a male infertility disorder with multiple morphological abnormalities of the sperm flagellum and loss of inner dynein arms, and mouse models reproduce this phenotype. Affected men generally lack respiratory symptoms, although a homozygous CFAP57 variant that prevents axonemal incorporation was reported in one individual with primary ciliary dyskinesia.

Disorders

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