KCNQ4

Potassium voltage-gated channel subfamily KQT member 4, also known as voltage-gated potassium channel subunit K_v7.4, is a protein that in humans is encoded by the KCNQ4 gene.

KCNQ4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2OVC, 4GOW
Identifiers
Aliases	KCNQ4, DFNA2, DFNA2A, KV7.4, potassium voltage-gated channel subfamily Q member 4
External IDs	OMIM: 603537; MGI: 1926803; HomoloGene: 78107; GeneCards: KCNQ4; OMA:KCNQ4 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p34.2 Start 40,783,787 bp End 40,840,452 bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4|4 D2.1 Start 120,553,335 bp End 120,605,809 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in retinal pigment epithelium muscle layer of sigmoid colon right coronary artery gastric mucosa parotid gland popliteal artery tibial arteries thoracic aorta ascending aorta left coronary artery Top expressed in digastric muscle lumbar spinal ganglion extraocular muscle muscle of thigh knee joint retinal pigment epithelium temporal muscle vastus lateralis muscle sternocleidomastoid muscle thoracic diaphragm More reference expression data BioGPS More reference expression data
Gene ontology Molecular function potassium channel activity voltage-gated ion channel activity ion channel activity protein binding voltage-gated potassium channel activity delayed rectifier potassium channel activity calmodulin binding Cellular component integral component of membrane membrane voltage-gated potassium channel complex plasma membrane basal plasma membrane Biological process regulation of ion transmembrane transport ion transport hearing potassium ion transport transmembrane transport potassium ion transmembrane transport inner ear morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9132 60613 Ensembl ENSG00000117013 ENSMUSG00000028631 UniProt P56696 Q9JK97 RefSeq (mRNA) NM_004700 NM_172163 NM_001081142 RefSeq (protein) NP_004691 NP_751895 NP_001074611 Location (UCSC) Chr 1: 40.78 – 40.84 Mb Chr 4: 120.55 – 120.61 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene.

Clinical significance

The current generated by this channel is inhibited by muscarinic acetylcholine receptor M1 and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene.

Ligands

• ML213: KCNQ2/Q4 channel opener.

See also

• Voltage-gated potassium channel

Further reading

• Coucke PJ, Van Hauwe P, Kelley PM, et al. (1999). "Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families". Hum. Mol. Genet. 8 (7): 1321–8. doi:10.1093/hmg/8.7.1321. PMID 10369879.
• Talebizadeh Z, Kelley PM, Askew JW, et al. (2000). "Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss". Hum. Mutat. 14 (6): 493–501. doi:10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P. PMID 10571947. S2CID 13288075.
• Selyanko AA, Hadley JK, Wood IC, et al. (2000). "Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors". J. Physiol. 522 (3): 349–55. doi:10.1111/j.1469-7793.2000.t01-2-00349.x. PMC 2269765. PMID 10713961.
• Van Hauwe P, Coucke PJ, Ensink RJ, et al. (2000). "Mutations in the KCNQ4 K+ channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region". Am. J. Med. Genet. 93 (3): 184–7. doi:10.1002/1096-8628(20000731)93:3<184::AID-AJMG4>3.0.CO;2-5. PMID 10925378.
• Beisel KW, Nelson NC, Delimont DC, Fritzsch B (2001). "Longitudinal gradients of KCNQ4 expression in spiral ganglion and cochlear hair cells correlate with progressive hearing loss in DFNA2". Brain Res. Mol. Brain Res. 82 (1–2): 137–49. doi:10.1016/S0169-328X(00)00204-7. PMID 11042367.
• Søgaard R, Ljungstrøm T, Pedersen KA, et al. (2001). "KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology". Am. J. Physiol., Cell Physiol. 280 (4): C859–66. doi:10.1152/ajpcell.2001.280.4.C859. PMID 11245603. S2CID 7891527.
• Van Camp G, Coucke PJ, Akita J, et al. (2002). "A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment". Hum. Mutat. 20 (1): 15–9. doi:10.1002/humu.10096. PMID 12112653. S2CID 22495155.
• Stern RE, Lalwani AK (2003). "Audiologic evidence for further genetic heterogeneity at DFNA2". Acta Otolaryngol. 122 (7): 730–5. doi:10.1080/003655402/000028059. PMID 12484650.
• Schwake M, Jentsch TJ, Friedrich T (2003). "A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly". EMBO Rep. 4 (1): 76–81. doi:10.1038/sj.embor.embor715. PMC 1315815. PMID 12524525.
• Li Y, Langlais P, Gamper N, et al. (2004). "Dual phosphorylations underlie modulation of unitary KCNQ K(+) channels by Src tyrosine kinase". J. Biol. Chem. 279 (44): 45399–407. doi:10.1074/jbc.M408410200. PMID 15304482.
• Chambard JM, Ashmore JF (2005). "Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway". Pflügers Arch. 450 (1): 34–44. doi:10.1007/s00424-004-1366-2. PMID 15660259. S2CID 21570482.
• Van Laer L, Carlsson PI, Ottschytsch N, et al. (2006). "The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss". Hum. Mutat. 27 (8): 786–95. doi:10.1002/humu.20360. PMID 16823764. S2CID 25357017.
• Van Eyken E, Van Laer L, Fransen E, et al. (2006). "KCNQ4: a gene for age-related hearing impairment?". Hum. Mutat. 27 (10): 1007–16. doi:10.1002/humu.20375. PMID 16917933. S2CID 8912727.
• Su CC, Yang JJ, Shieh JC, et al. (2007). "Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic deafness from Taiwan". Audiol. Neurootol. 12 (1): 20–6. doi:10.1159/000096154. PMID 17033161. S2CID 25256223.
• Jensen HS, Grunnet M, Olesen SP (2007). "Inactivation as a New Regulatory Mechanism for Neuronal Kv7 Channels". Biophys. J. 92 (8): 2747–56. Bibcode:2007BpJ....92.2747J. doi:10.1529/biophysj.106.101287. PMC 1831682. PMID 17237198.
• Howard RJ, Clark KA, Holton JM, Minor DL (2007). "Structural Insight into KCNQ (Kv7) Channel Assembly and Channelopathy". Neuron. 53 (5): 663–75. doi:10.1016/j.neuron.2007.02.010. PMC 3011230. PMID 17329207.
• Iannotti FA, Panza E, Barrese V, Viggiano D, Soldovieri MV, Taglialatela M (March 2010). "Expression, localization, and pharmacological role of Kv7 potassium channels in skeletal muscle proliferation, differentiation, and survival after myotoxic insults". J. Pharmacol. Exp. Ther. 332 (3): 811–20. doi:10.1124/jpet.109.162800. PMID 20040580. S2CID 17248733.
• Iannotti FA, Barrese V, Formisano L, Taglialatela M (Feb 2013). "Specification of skeletal muscle differentiation by repressor element-1 silencing transcription factor (REST)-regulated Kv7.4 potassium channels". Mol Biol Cell. 24 (3): 274–84. doi:10.1091/mbc.E11-12-1044. PMC 3564528. PMID 23242999.

External links

• GeneReviews/NCBI/NIH/UW entry on Deafness and Hereditary Hearing Loss Overview
• KCNQ4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• GeneReviews/NCBI/NIH/UW entry on DFNA2 Nonsyndromic Hearing Loss

This article incorporates text from the United States National Library of Medicine, which is in the public domain.