<i>CCDC9</i> is identified as a novel candidate gene of severe asthenozoospermia

Owing to less than 1% of motile spermatozoa in the ejaculated semen, severe asthenozoospermia is a serious threat to the male reproductive health. Herein, we identified a novel homozygous variant in <i>CCDC9</i> (NC_000019.9: g.47763960C&gt;T, NM_015603.3, NP_056418.1: p. Ser109Leu) in a patient from a consanguineous family. The variant was highly pathogenic and was predicted to be a candidate gene for asthenozoospermia through <i>in silico</i> analysis. The CCDC9 protein levels were significantly low and its morphology and ultrastructure were severely damaged in the spermatozoa containing the novel variant. Therefore, <i>CCDC9</i> may be a novel pathogenic gene associated with severe asthenozoospermia. <b>Abbreviations</b>: <i>CCDC9</i>: coiled-coil domain containing 9; AZS: asthenozoospermia; MP: midpiece; MS: mitochondrial sheath; ODF: outer dense fiber; CP: central pair; DMT: doublet microtubule; IDA: inner dynein arm; ODA: outer dynein arm.