KCNQ4 Gene: Potassium Voltage-Gated Channel Subfamily Q Member 4
Genetic insights into KCNQ4-related hearing loss and channelopathies
Gene Information Card
| Symbol | KCNQ4 |
|---|---|
| Full Name | Potassium Voltage-Gated Channel Subfamily Q Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.2 |
| NCBI Gene ID | 9133 ncbi.nlm.nih.gov/gene/9133 |
| Ensembl ID | ENSG00000158321 |
| UniProt ID | P56696 |
| OMIM ID | 603537 |
| HGNC ID | 6294 |
| Aliases | DFNA2, KQT-like 4, Kv7.4, potassium channel KQT-like 4 |
Description
The KCNQ4 gene encodes the potassium voltage-gated channel subfamily Q member 4 (Kv7.4), a voltage-gated potassium channel critical for maintaining potassium ion homeostasis in the inner ear and central nervous system. Mutations in KCNQ4 are a well-established cause of autosomal dominant nonsyndromic hearing loss, specifically DFNA2. The channel is also expressed in other tissues, including the brain and smooth muscle, where it contributes to neuronal excitability and vascular tone regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal Dominant Nonsyndromic Hearing Loss (DFNA2) | Missense or splice-site mutations in KCNQ4 lead to reduced potassium conductance in cochlear outer hair cells, causing progressive hearing loss. | ClinVar, OMIM |
| Progressive High-Frequency Hearing Loss | Dominant-negative mutations impair channel function, leading to hair cell degeneration. | ClinVar, OMIM |
| Possibly related to cardiovascular phenotypes | Altered KCNQ4 expression in vascular smooth muscle may affect blood pressure regulation, but evidence is limited. | UniProt, literature (not fully validated) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cochlea | Not available (nTPM not applicable) | High expression in outer hair cells (protein level) |
| Brain | ~10.2 | Moderate expression in multiple regions (GTEx) |
| Kidney | ~5.3 | Low expression |
| Heart | ~3.1 | Low expression |
| Skeletal Muscle | ~1.5 | Very low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Not available | Used for heterologous expression studies |
| SH-SY5Y | Not available | Endogenous expression reported in neuronal cell lines |
| HL-1 (cardiomyocyte) | Not available | Expression detected in cardiac myocytes (low) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.211C>T (p.Arg71Trp) | Missense | Rare (found in DFNA2 families) | Dominant-negative effect, reduces potassium current |
| c.883G>A (p.Gly295Ser) | Missense | Rare | Loss of function, trafficking defect |
| c.1022T>C (p.Leu341Pro) | Missense | Rare | Dominant-negative, reduced channel activity |
| c.1492C>T (p.Arg498Ter) | Nonsense | Rare | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated non-functional channels, causing haploinsufficiency.
Gain of Function (GOF)
Not commonly reported; most pathogenic mutations are loss-of-function or dominant-negative.
Dominant Negative (DN)
Many missense mutations exert dominant-negative effects by co-assembling with wild-type subunits and impairing channel function.
View complete mutation data：
Gene Ontology (GO)
| • Voltage-gated potassium channel activity | • Potassium ion transmembrane transport |
| • Ion channel complex | • Plasma membrane |
| • Cellular response to electrical stimulus |
Pathways
• Potassium channel signaling
• Ion transport
• Hearing and ear morphogenesis
Protein Summary
The KCNQ4 protein (Kv7.4) is a six-transmembrane-domain voltage-gated potassium channel that forms homotetrameric or heterotetrameric complexes with other KCNQ subunits. It mediates the M-current in neurons and regulates potassium efflux in inner ear hair cells, essential for maintaining the endocochlear potential. The channel is activated by membrane depolarization and modulated by PIP2 and calmodulin. Mutations causing hearing loss typically disrupt channel gating, trafficking, or assembly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KCNQ4 Knockout HEK293 Cell Line | EDJ-KQ6469 | Human | 9132 | Details Get a Quote |
| KCNQ4 Knockout HCT 116 Cell Line | EDJ-KQ30561 | Human | 9132 | Details Get a Quote |
| KCNQ4 Knockout HeLa Cell Line | EDJ-KQ55091 | Human | 9132 | Details Get a Quote |
| KCNQ4 Knockout A-549 Cell Line | EDJ-KQ63570 | Human | 9132 | Details Get a Quote |
| KCNQ4(p.G285S, c.853G>A)Point Mutation in HEK293T Cell Line | EDC90024 | Human | 9132 | Details Get a Quote |
| Kcnq4 Overexpression HEK293T Stable Cell Line | EDC01714 | Human | 60613 | Details Get a Quote |
