Potassium voltage-gated channel subfamily H member 4 (KCNH4)

Potassium voltage-gated channel subfamily H member 4 (KCNH4) is a pore-forming (alpha) subunit of voltage-gated delayed rectifier potassium channels, part of the larger KCNH (eag/ELK/ERG) family[2][3][4][7]. KCNH4 channels are tetrameric, each subunit containing six transmembrane segments and specialized voltage-sensing and pore domains[2][3][5]. These channels activate at more negative voltages and exhibit fast, prepulse-independent kinetics, contributing to the repolarization phase of the membrane potential and modulating action potential firing in neurons[2][4]. KCNH4 is expressed predominantly in the brain and is involved in setting the electrical excitability of neurons and shaping action potential characteristics[7]. While other KCNH family members like KCNH2 (hERG) are established drug targets in cardiac and oncological indications, specific drugs or disease associations for KCNH4 remain unreported. Despite the lack of direct small-molecule ligands or clinical biomarkers, KCNH4’s structural and functional properties implicate it as an important modulator within neural circuits[2][3][7]. Additional context: - KCNH4 channels do not bind cyclic nucleotides directly, instead containing a “cyclic nucleotide-binding homology domain” regulated by an intrinsic ligand within their C-terminal region[3]. - They are categorized within the *Kv12* subfamily (Kv12.3), which are slowly activating voltage-gated potassium channels[5]. - Dysfunction in related KCNH channels is implicated in long QT syndrome and cancer, but direct disease links for KCNH4 are not described in the literature[3][7]. Note: - No therapeutically approved drugs, clinical biomarkers, or specific patient safety concerns have been reported for KCNH4 as of the current knowledge base[4][7]. - Disease and functional roles are inferred from family characteristics and expression profile; caution should be used when extrapolating to clinical significance for KCNH4 specifically.

Other names

Voltage-gated delayed rectifier potassium channel KCNH4BEC2ELK channel 1ELK1Kv12.3brain-specific eag-like channel 2ether-a-go-go-like potassium channel 1voltage-gated potassium channel subunit Kv12.3potassium channel, voltage gated eag related subfamily H, member 4