Target intelligence / Profile preview

Potassium voltage-gated channel subfamily Q member 4 (KCNQ4) (KCNQ4)

Target
KCNQ4
Molecular classification
Ion channel, Voltage-gated potassium channel, Kv7 family
01

Overview

Potassium voltage-gated channel subfamily Q member 4 (KCNQ4), also known as Kv7.4, is a transmembrane protein that forms voltage-gated potassium channels, primarily as homotetramers in the inner ear (UniProt P56696). It is localized to the outer hair cells of the cochlea, where it plays a vital role in potassium ion recycling and maintaining the electrical environment necessary for auditory transduction (PubMed: 10072428). Mutations in the KCNQ4 gene are the underlying cause of DFNA2, an autosomal dominant form of progressive nonsyndromic hearing loss (PubMed: 10712414). Beyond the auditory system, KCNQ4 is expressed in vascular smooth muscle cells and contributes to the regulation of vascular tone and blood pressure (PubMed: 24928851). Pharmacological research focuses on developing selective KCNQ4 activators, such as ML213, to treat hearing loss and tinnitus while minimizing off-target effects on other Kv7 subtypes (PubMed: 21653227). However, the high structural similarity between Kv7 family members poses a challenge for achieving the necessary drug selectivity to avoid central nervous system side effects.

Other names
Kv7.4Potassium channel subunit alpha Kv7.4DFNA2KQT-like 4
02

Mechanism of action

Positive allosteric modulation (opening) of the channel to increase potassium efflux and stabilize membrane potential.

03

Biological functions

Potassium ion transportRegulation of membrane potentialSensory perception of soundAuditory signal transduction
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Disease associations

Nonsyndromic hearing lossDFNA2ATinnitusHypertension
05

Safety considerations

Off-target CNS effects (dizziness, somnolence)Potential hypotensionUrinary retention
06

Interacting drugs

Retigabine

7 more in the full profile.

07

Biomarkers

KCNQ4 gene mutationsAudiometric thresholds

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