CYBRD1

CYBRD1 is a human gene that encodes the duodenal cytochrome b (Dcytb), a ferrireductase located on the apical membrane of enterocytes in the small intestine. The protein is a transmembrane enzyme that transfers electrons from cellular reductants, such as ascorbate, to ferric iron (Fe3+), reducing it to ferrous iron (Fe2+) for uptake by the metal transporter DMT1 (SLC11A2). This reductive step is an essential part of dietary iron absorption and supports systemic iron homeostasis.

In addition to its intestinal role, Dcytb-like ferrireductase activity has been reported in other tissues, but the best-established function is in the intestinal iron pathway. Dcytb cooperates with other components of iron handling, including ferroportin and the ferroxidase hephaestin, to ensure efficient iron uptake and export into the circulation.

Expression of CYBRD1 is highest in the duodenum, reflecting its primary role in dietary iron absorption, with detectable but lower levels in other tissues. Expression is influenced by iron status and physiological conditions, aligning with the body’s needs for iron regulation.

Clinical and genetic aspects of CYBRD1 focus on its contribution to iron metabolism. Variants and altered CYBRD1 function have been investigated for associations with iron parameters and anemia risk, though findings across studies can be inconclusive. In animal models, loss of CYBRD1 function impairs iron absorption and can lead to iron-restricted hematologic status, supporting its important role in iron metabolism.

CYBRD1 is also known as duodenal cytochrome b (Dcytb) and is part of the ferrireductase family involved in the initial steps of iron uptake at the intestinal mucosa.