Cation channel sperm-associated protein 3 (CATSPER3)

Cation channel sperm-associated protein 3 (CATSPER3) is a pore-forming subunit of the CatSper channel, a sperm-specific calcium ion channel complex essential for male fertility[1][2][5]. CATSPER3 is exclusively expressed in testis, localized to the sperm flagellum, and is required for sperm hyperactivation and acrosome reaction, both critical for successful fertilization[1][3][5]. The CatSper channel is activated by alkalinization, progesterone, and prostaglandins, and disruption of any CatSper subunit—including CATSPER3—results in male infertility due to defects in sperm motility[1][3][5]. CATSPER3 is a potential target for male contraceptives and a biomarker for certain forms of male infertility[1][3]. No clinically approved therapeutic targeting CATSPER3 exists; research focuses on infertility diagnosis and male contraceptive interventions. CATSPER3 is the human gene encoding this subunit (UniProt Q86XQ3), and all four CatSper subunits (CatSper1-4) are required to assemble a functional channel; their expression is co-dependent in sperm[5]. The CatSper family is unique to sperm and does not have widespread tissue distribution, limiting systemic side effects for specific inhibitors[1][5].

Other names

CatSper3CACRCCa(v)-like proteinOne-repeat calcium channel-like proteincalcium channel repeat containing 1putative ion channel CatSper3

Activation by progesterone/prostaglandins shifts voltage dependence, promoting channel opening and calcium influx in sperm—facilitates motility and acrosome reaction. Blockade by divalent cations or specific inhibitors prevents calcium influx, suppressing sperm motility and function.