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Gene and Protein Information  |
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| Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 6 | 1 | 932 | 6q13 | KCNQ5 | potassium voltage-gated channel subfamily Q member 5 | 13 |
| Mouse | 6 | 1 | 933 | 1 A4 | Kcnq5 | potassium voltage-gated channel, subfamily Q, member 5 | 12 |
| Rat | 6 | 1 | 951 | 9q13 | Kcnq5 | potassium voltage-gated channel subfamily Q member 5 | |
| Previous and Unofficial Names |
| Kcnq5l | potassium channel, voltage gated KQT-like subfamily Q, member 5 | potassium channel, voltage-gated KQT-like subfamily Q, member 5 | potassium voltage-gated channel |
| Database Links |
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| Alphafold | Q9NR82 (Hs), Q9JK45 (Mm) |
| ChEMBL Target | CHEMBL2925 (Hs) |
| Ensembl Gene | ENSG00000185760 (Hs), ENSMUSG00000028033 (Mm), ENSRNOG00000013781 (Rn) |
| Entrez Gene | 56479 (Hs), 226922 (Mm), 259273 (Rn) |
| Human Protein Atlas | ENSG00000185760 (Hs) |
| KEGG Gene | hsa:56479 (Hs), mmu:226922 (Mm), rno:259273 (Rn) |
| OMIM | 607357 (Hs) |
| Pharos | Q9NR82 (Hs) |
| RefSeq Nucleotide | NM_019842 (Hs), NM_023872 (Mm), NM_001134643 (Rn) |
| RefSeq Protein | NP_062816 (Hs), NP_076361 (Mm), NP_001128115 (Rn) |
| UniProtKB | Q9NR82 (Hs), Q9JK45 (Mm) |
| Wikipedia | KCNQ5 (Hs) |
| Associated Proteins |
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| Associated Protein Comments | ||||||||||||||||||||||||
| KCNE1 and KCNE3 are auxiliary subunits in skeletal muscle [18]. Gating and modulation: Ca2+-calmodulin reduces the currents produced by KCNQ2, KCNQ4 and KCNQ5, but not those of KCNQ1 and KCNQ3 [6]. PIP2 stabilizes the channel in the open state [7,14]. In mesenteric artery smooth muscle cells, protein kinase C phosphorylates both KCNQ4 and KCNQ5 heteromers, thereby reducing the KCNQ4/KCNQ5 currents in response to vasoconstriction [3]. |
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| Functional Characteristics |
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| M current as heteromeric KV7.3/KV7.5 | |
| Ion Selectivity and Conductance |
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| Ion Selectivity and Conductance Comments | ||||||
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| Voltage Dependence |
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Download all structure-activity data for this target as a CSV file 
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| Tissue Distribution
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| Physiological Functions
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| Clinically-Relevant Mutations and Pathophysiology Comments |
| Dysfunction of the heteromeric KCNQ3/KCNQ5 potassium channel is associated with autism spectrum disorders [9]. |
| General Comments |
| The M current is a slowly activating and deactivating potassium conductance that plays a critical role in determining the sub-threshold excitability of neurones as well as the responsiveness to synaptic inputs. The M current was first described in peripheral sympathetic neurones, and differential expression of this conductance produces subtypes of sympathetic neurones with distinct firing patterns. The M current is also expressed in many neurons in the central nervous system. The M-current is mediated by members of the Kv7 family, which form a heterotetrameric channel consisting of KCNQ3 subunits associated with either KCNQ2 or KCNQ5 subunits. Expression of KCNQ2, KCNQ3 and KCNQ5 proteins mostly overlaps with distribution of M current [13,19]. |
1. Bal M, Zhang J, Zaika O, Hernandez CC, Shapiro MS. (2008) Homomeric and heteromeric assembly of KCNQ (Kv7) K+ channels assayed by total internal reflection fluorescence/fluorescence resonance energy transfer and patch clamp analysis. J Biol Chem, 283 (45): 30668-76. [PMID:18786918]
2. Bentzen BH, Schmitt N, Calloe K, Dalby Brown W, Grunnet M, Olesen SP. (2006) The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology, 51 (6): 1068-77. [PMID:16904708]
3. Brueggemann LI, Mackie AR, Cribbs LL, Freda J, Tripathi A, Majetschak M, Byron KL. (2014) Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels. J Biol Chem, 289 (4): 2099-111. [PMID:24297175]
4. Brueggemann LI, Moran CJ, Barakat JA, Yeh JZ, Cribbs LL, Byron KL. (2007) Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells. Am J Physiol Heart Circ Physiol, 292 (3): H1352-63. [PMID:17071736]
5. Dupuis DS, Schrøder RL, Jespersen T, Christensen JK, Christophersen P, Jensen BS, Olesen SP. (2002) Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352. Eur J Pharmacol, 437 (3): 129-37. [PMID:11890900]
6. Gamper N, Li Y, Shapiro MS. (2005) Structural requirements for differential sensitivity of KCNQ K+ channels to modulation by Ca2+/calmodulin. Mol Biol Cell, 16 (8): 3538-51. [PMID:15901836]
7. Gamper N, Shapiro MS. (2007) Regulation of ion transport proteins by membrane phosphoinositides. Nat Rev Neurosci, 8 (12): 921-34. [PMID:17971783]
8. Gamper N, Stockand JD, Shapiro MS. (2003) Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase. J Neurosci, 23 (1): 84-95. [PMID:12514204]
9. Gilling M, Rasmussen HB, Calloe K, Sequeira AF, Baretto M, Oliveira G, Almeida J, Lauritsen MB, Ullmann R, Boonen SE et al.. (2013) Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders. Front Genet, 4: 54. [PMID:23596459]
10. Haitin Y, Attali B. (2008) The C-terminus of Kv7 channels: a multifunctional module. J Physiol (Lond.), 586 (7): 1803-10. [PMID:18218681]
11. Huang H, Trussell LO. (2011) KCNQ5 channels control resting properties and release probability of a synapse. Nat Neurosci, 14 (7): 840-7. [PMID:21666672]
12. Jensen HS, Callø K, Jespersen T, Jensen BS, Olesen SP. (2005) The KCNQ5 potassium channel from mouse: a broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes. Brain Res Mol Brain Res, 139 (1): 52-62. [PMID:15963599]
13. Lerche C, Scherer CR, Seebohm G, Derst C, Wei AD, Busch AE, Steinmeyer K. (2000) Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M-current diversity. J Biol Chem, 275 (29): 22395-400. [PMID:10787416]
14. Li Y, Gamper N, Hilgemann DW, Shapiro MS. (2005) Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J Neurosci, 25 (43): 9825-35. [PMID:16251430]
15. Li Y, Gamper N, Shapiro MS. (2004) Single-channel analysis of KCNQ K+ channels reveals the mechanism of augmentation by a cysteine-modifying reagent. J Neurosci, 24 (22): 5079-90. [PMID:15175377]
16. Manville RW, Abbott GW. (2018) Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels. Mol Pharmacol, 94 (4): 1155-1163. [PMID:30021858]
17. Ng FL, Davis AJ, Jepps TA, Harhun MI, Yeung SY, Wan A, Reddy M, Melville D, Nardi A, Khong TK et al.. (2011) Expression and function of the K+ channel KCNQ genes in human arteries. Br J Pharmacol, 162 (1): 42-53. [PMID:20840535]
18. Roura-Ferrer M, Etxebarria A, Solé L, Oliveras A, Comes N, Villarroel A, Felipe A. (2009) Functional implications of KCNE subunit expression for the Kv7.5 (KCNQ5) channel. Cell Physiol Biochem, 24 (5-6): 325-34. [PMID:19910673]
19. Schroeder BC, Hechenberger M, Weinreich F, Kubisch C, Jentsch TJ. (2000) KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents. J Biol Chem, 275 (31): 24089-95. [PMID:10816588]
20. Shah M, Mistry M, Marsh SJ, Brown DA, Delmas P. (2002) Molecular correlates of the M-current in cultured rat hippocampal neurons. J Physiol (Lond.), 544 (Pt 1): 29-37. [PMID:12356878]
21. Stott JB, Jepps TA, Greenwood IA. (2014) K(V)7 potassium channels: a new therapeutic target in smooth muscle disorders. Drug Discov Today, 19 (4): 413-24. [PMID:24333708]
22. Tzingounis AV, Heidenreich M, Kharkovets T, Spitzmaul G, Jensen HS, Nicoll RA, Jentsch TJ. (2010) The KCNQ5 potassium channel mediates a component of the afterhyperpolarization current in mouse hippocampus. Proc Natl Acad Sci USA, 107 (22): 10232-7. [PMID:20534576]
23. Wang L, Qiao GH, Hu HN, Gao ZB, Nan FJ. (2019) Discovery of Novel Retigabine Derivatives as Potent KCNQ4 and KCNQ5 Channel Agonists with Improved Specificity. ACS Med Chem Lett, 10 (1): 27-33. [PMID:30655942]
24. Xiong Q, Sun H, Li M. (2007) Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol, 3 (5): 287-96. [PMID:17435769]
