KCNQ4

KCNQ4
Available structures PDB Ortholog search:PDBeRCSB 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 40,783,787bp End 40,840,452bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4|4 D2.1 Start 120,553,335bp End 120,605,809bp
RNA expressionpattern 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 PubMedsearch
Wikidata
View/Edit Human View/Edit Mouse

Potassium voltage-gated channel subfamily KQT member 4,also known asvoltage-gated potassium channel subunit K_v7.4,is aproteinthat in humans is encoded by theKCNQ4gene.

Function

The protein encoded by this gene forms apotassium channelthat is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of thecochlea.The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by theKCNQ3gene.

Clinical significance

The current generated by this channel is inhibited bymuscarinic acetylcholine receptor M1and activated byretigabine,a novel anti-convulsant drug. Defects in this gene are a cause ofnonsyndromic sensorineural deafnesstype 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.PMID10369879.
• 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.PMID10571947.S2CID13288075.
• 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.PMC2269765.PMID10713961.
• 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.PMID10925378.
• 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.PMID11042367.
• 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.PMID11245603.S2CID7891527.
• 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.PMID12112653.S2CID22495155.
• Stern RE, Lalwani AK (2003). "Audiologic evidence for further genetic heterogeneity at DFNA2".Acta Otolaryngol.122(7): 730–5.doi:10.1080/003655402/000028059.PMID12484650.
• 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.PMC1315815.PMID12524525.
• 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.PMID15304482.
• 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.PMID15660259.S2CID21570482.
• 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.PMID16823764.S2CID25357017.
• 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.PMID16917933.S2CID8912727.
• 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.PMID17033161.S2CID25256223.
• 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.PMC1831682.PMID17237198.
• 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.PMC3011230.PMID17329207.
• 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.PMID20040580.S2CID17248733.
• 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.PMC3564528.PMID23242999.

External links

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

This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.