KCNE5 (Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 5), also known as KCNE1L (KCNE1-like), is a gene that encodes a regulatory subunit of voltage-gated potassium (Kv) channels. While historically associated primarily with cardiac physiology, emerging research suggests important roles in neuronal function and potential implications for neurodegenerative diseases[1].
| KCNE5 Gene | |
|---|---|
| Gene Symbol | KCNE5 |
| Alternative Names | KCNE1L, MinK-related peptide 1 |
| Full Name | Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 5 |
| Chromosomal Location | Xq23 |
| NCBI Gene ID | [286058](https://www.ncbi.nlm.nih.gov/gene/286058) |
| OMIM | [300638](https://omim.org/entry/300638) |
| Ensembl ID | ENSG00000124145 |
| UniProt ID | [Q9NZZ6](https://www.uniprot.org/uniprot/Q9NZZ6) |
| Protein Size | 144 amino acids |
The KCNE family consists of five members (KCNE1-5), each serving as a regulatory subunit for various potassium channels:
| KCNE | Gene | Partner Channels | Primary Tissue |
|---|---|---|---|
| KCNE1 | KCNE1 | KCNQ1 | Heart, inner ear |
| KCNE2 | KCNE2 | KCNQ1, hERG | Heart, brain |
| KCNE3 | KCNE3 | KCNQ2/3 | Brain, stomach |
| KCNE4 | KCNE4 | Kv1, Kv2 | Brain, other |
| KCNE5 | KCNE5 | Kv1, Kv3, KCNQ | Brain, heart |
KCNE proteins share a common topology:
KCNE5 modulates potassium channel function in several ways:
In the heart, KCNE5:
In the brain[2]:
KCNE5 associates with multiple neuronal Kv channels:
| Channel | Current | Function in Neurons |
|---|---|---|
| Kv1.x | IA, IK | Repolarization, action potential shape |
| Kv3.x | IK | High-frequency firing |
| KCNQ2/3 | M-current | Subthreshold excitability |
KCNE5 mutations are linked to cardiac disorders[4]:
| Tissue | Expression Level | Notes |
|---|---|---|
| Heart | High | Ventricular myocardium |
| Brain | Moderate | Cortex, hippocampus, cerebellum |
| Inner ear | Moderate | Hair cells |
| Kidney | Low | Tubular cells |
| Lung | Low | Alveolar cells |
| Target | Approach | Status |
|---|---|---|
| Kv channel activators | Openers to increase K+ efflux | Preclinical |
| KCNE5 modulators | Target the regulatory subunit | Discovery |
| Calcium channel blockers | Reduce Ca2+ influx | Clinical |
| Interactor | Type | Relationship |
|---|---|---|
| KCNQ2 | Channel | Functional partner |
| Kv1.x | Channel | Functional partner |
| Kv3.x | Channel | Functional partner |
| KCNE2 | Protein | Family member interaction |
Stocker M, et al. Calcium-activated potassium channels: molecular diversity and function. Physiological Reviews. 2004. ↩︎
Kohler M, et al. Small-conductance, calcium-activated potassium channels from mammalian brain. Science. 1996. ↩︎
Chen L, et al. Potassium channels in Alzheimer's disease: emerging therapeutic targets. Neuropharmacology. 2017. ↩︎
Abbott GW. KCNE5 and cardiac arrhythmia: molecular mechanisms and therapeutic implications. Journal of Molecular and Cellular Cardiology. 2012. ↩︎