KCNH1 (Potassium Voltage-Gated Channel Subfamily H Member 1), also known as Kv10.1 or EAG1 (Ether-à-go-go 1), is a voltage-gated potassium channel with unique properties in neuronal excitability, cell proliferation, and synaptic transmission. It is implicated in neurodevelopmental disorders, epilepsy, and potentially in neurodegenerative diseases[1][2].
| Property | Value |
|---|---|
| Gene Symbol | KCNH1 |
| Full Name | Potassium Voltage-Gated Channel Subfamily H Member 1 |
| Chromosomal Location | 1p36.33 |
| NCBI Gene ID | 3756 |
| OMIM | 603305 |
| Ensembl ID | ENSG00000128408 |
| UniProt ID | Q14721 |
KCNH1 is a 958-amino acid voltage-gated potassium channel[3]:
KCNH1 regulates neuronal membrane potential and excitability[4][5]:
KCNH1 modulates synaptic function through multiple mechanisms[6]:
KCNH1 mutations cause epileptic encephalopathies[7][8]:
Disease Mechanisms
Clinical Phenotypes
KCNH1 is associated with neurodevelopmental conditions[9]:
Emerging evidence suggests KCNH1 involvement in neurodegeneration[10]:
Targeting KCNH1 has therapeutic potential[11][12]:
| Approach | Target | Status |
|---|---|---|
| KCNH1 blockers | Antiepileptic | Preclinical |
| KCNH1 openers | Memory enhancement | Research |
| Gene therapy | Kv10.1 modulation | Experimental |
Jentsch TJ. Neuronal KCNQ potassium channels: physiology and role in disease. 2000. ↩︎
Bialer M, Johannessen SI, Levy RH, et al. Progress report on new antiepileptic drugs: a summary of the EILAT X and EILAT X3. 2013. ↩︎
Long SB, Campbell EB, Mackinnon R. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. 2005. ↩︎
Varga AW, Yuan LL, Anderson AE, et al. [Calcium-activated potassium channels](https://doi.org/10.1016/S0896-6273(04). 2004. ↩︎
Storm JF. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells. 1987. ↩︎
Hu H, Vervaeke K, Storm JF. [M-channels (Kv7/KCNQ channels) regulate synaptic integration](https://doi.org/10.1016/S0896-6273(02). 2002. ↩︎
Torkamani A, Bersell K, Jorge BS, et al. De novo KCNH1 mutations cause epileptic encephalopathy. 2014. ↩︎
Ufongene C, Raynes-Greenow C, Mcgrath N, et al. KCNH1-related neurodevelopmental disorders. 2023. ↩︎
Barth AS, Tomaselli GF. KCNH1 mutations associated with neurodevelopmental disorders: clinical features and therapeutic implications. 2016. ↩︎
Plant LD, Dementieva IS, Markova O, et al. KCNH1 channels in Alzheimer's disease. 2020. ↩︎
Brown BM, Shim H, Christopherson P, et al. Kv channel modulators for the treatment of neurological disorders. 2018. ↩︎
Barcia G, Fleming MR, Deligniere L, et al. De novo missense mutations in the Kv10.1 channel cause early infantile epileptic encephalopathy. 2014. ↩︎