Voltage-gated hydrogen channel 1 (Hv1) (HVCN1)

The Voltage-gated hydrogen channel 1 (Hv1), encoded by the HVCN1 gene, is a unique ion channel that lacks a traditional pore domain, instead conducting protons through its voltage-sensor domain (VSD) (UniProt Q96D96). It is primarily expressed in immune cells, where it facilitates the efflux of protons to compensate for the electrogenic activity of NADPH oxidase (NOX) during the respiratory burst, thereby maintaining intracellular pH and sustaining reactive oxygen species (ROS) production (PubMed: 36640925). Beyond immunity, Hv1 plays critical roles in sperm capacitation, airway pH regulation, and B-cell signaling (PubMed: 20144758). In disease, Hv1 is frequently overexpressed in various cancers, including breast and colorectal cancer, where it promotes tumor cell survival, migration, and invasion by regulating the acidic microenvironment (PubMed: 25101684). It is also implicated in neuroinflammatory damage following ischemic stroke and in Parkinson's disease due to its role in microglial ROS production (PubMed: 22466566, 35501344). Pharmacological inhibition of Hv1 using small molecules like 2-guanidinobenzimidazole (2-GBI) or novel inhibitors like YHV98-4 is being explored as a therapeutic strategy for malignancy, chronic pain, and neurodegeneration (PubMed: 35501344, 38850134). While no Hv1-targeted drugs have reached clinical approval, the channel remains a promising target for modulating pH-dependent cellular processes in pathological states (Wikipedia).

Other names

HVCN1Hv1Hydrogen voltage-gated channel 1Voltage-sensor domain-only proteinVSOP

Inhibition of proton efflux to modulate intracellular pH and suppress NADPH oxidase-dependent reactive oxygen species production.