Solute carrier family 9 member C1 (SLC9C1)

Solute carrier family 9 member C1 (SLC9C1), also known as NHE-10 or sNHE, is a transporter protein primarily expressed in sperm and testis, encoded by the SLC9C1 gene. SLC9C1 is a unique member of the sodium-hydrogen exchanger (NHE) family that functions as a voltage- and cyclic nucleotide-regulated Na+/H+ exchanger, promoting intracellular alkalinization by extruding protons in exchange for sodium ions. Unlike other NHEs, SLC9C1 contains both a voltage-sensing domain (VSD) and a cyclic-nucleotide binding domain (CNBD), facilitating rapid and regulated changes in intracellular pH critical for sperm motility and male fertility. SLC9C1 activation is essential for hyperactivation and fertilization, and mutations disrupting its function can cause male infertility. Additionally, SLC9C1 expression in osteoclasts suggests a role in bone metabolism, and experimental antibodies targeting SLC9C1 have been explored to inhibit bone resorption. Pathogenic mutations in SLC9C1 have been linked to reproductive disorders in humans, such as asthenozoospermia, and may also be associated with other diseases like Dent’s disease.

Other names

SLC9A10NHE-10Na(+)/H(+) exchanger 10Sodium/hydrogen exchanger 10Solute carrier family 9 member 10Sperm-specific Na(+)/H(+) exchangersNHEsperm-NHE

Inhibition of SLC9C1 function (e.g., by antibody) reduces bone resorption\nModulation of sodium/proton exchange by affecting voltage and cAMP gating