Voltage-gated hydrogen channel 1 (HVCN1)

Voltage-gated hydrogen channel 1 (HVCN1) is a proton-selective ion channel that conducts outward proton currents in response to changes in membrane potential or intracellular acidification[2][3][5]. It lacks a canonical ion channel pore domain and mediates proton permeability via its voltage sensor domain[2][5]. HVCN1 is expressed in various cell types, most notably immune cells (such as B cells, T cells, and phagocytes), where it is essential for maintaining pH homeostasis and supporting the production of reactive oxygen species by NADPH oxidase during the respiratory burst[1][2]. In immune cells, HVCN1 plays a nonredundant role in regulating intracellular acidification, signaling, cell proliferation, effector function, and cell metabolism. It is also involved in sperm function by sustaining bicarbonate levels for capacitation and regulates airway epithelial pH[2][5]. Increased HVCN1 expression is associated with several cancers, where it may promote survival in acidic microenvironments[1][2]. Antagonists of HVCN1 are being explored clinically, but complete inhibition may risk immune deficiency or dysfunction due to its role in leukocyte physiology[1].\n\n**Note:** No approved drugs are currently on the market specifically targeting HVCN1, but antagonists are under investigation for cancer therapy and immune modulation[1]. HVCN1 is regarded as a valid ion channel therapeutic target, especially in cancer and immune regulation[1][2][5].

Other names

Hv1VSOPVoltage sensor domain-only proteinUNQ578/PRO1140MGC15619

Inhibition: Blocks proton efflux, leading to intracellular acidification and impaired ROS generation[1]. Potential modulation for immune suppression or anti-cancer effects[1].