KvLQT2

KCNQ2
Identifiers
Aliases	KCNQ2 , BFNC, BFNS1, EBN, EBN1, EIEE7, ENB1, HNSPC, KCNA11, KV7.2, KVEBN1, potassium voltage-gated channel subfamily Q member 2, DEE7
External IDs	OMIM: 602235; MGI: 1309503; HomoloGene: 26174; GeneCards: KCNQ2; OMA:KCNQ2 - orthologs
Gene location (Human) Chr. Chromosome 20 (human) [1] Band 20q13.33 Start 63,400,208 bp [1] End 63,472,677 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2 H4|2 103.57 cM Start 180,717,372 bp [2] End 180,777,093 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum right frontal lobe right testis ganglionic eminence amygdala left testis nucleus accumbens dorsolateral prefrontal cortex superior frontal gyrus caudate nucleus Top expressed in Region I of hippocampus proper CA3 field perirhinal cortex entorhinal cortex subiculum dentate gyrus primary visual cortex nucleus accumbens facial motor nucleus superior frontal gyrus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ankyrin binding ion channel activity voltage-gated ion channel activity voltage-gated potassium channel activity potassium channel activity calmodulin binding protein binding delayed rectifier potassium channel activity Cellular component axon initial segment node of Ranvier membrane integral component of membrane integral component of plasma membrane voltage-gated potassium channel complex plasma membrane Biological process regulation of ion transmembrane transport ion transport transmembrane transport nervous system development chemical synaptic transmission potassium ion transport potassium ion transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3785 16536 Ensembl ENSG00000075043 ENSG00000281151 ENSMUSG00000016346 UniProt O43526 Q9Z351 RefSeq (mRNA) NM_004518 NM_172106 NM_172107 NM_172108 NM_172109 NM_001382235 NM_001003824 NM_001003825 NM_001006668 NM_001006669 NM_001006674 NM_001006675 NM_001006676 NM_001006677 NM_001006678 NM_001006679 NM_001006680 NM_010611 NM_001302888 RefSeq (protein) NP_004509 NP_742104 NP_742105 NP_742106 NP_742107 NP_001369164 NP_001003824 NP_001003825 NP_001006669 NP_001006670 NP_001006675 NP_001289817 NP_034741 Location (UCSC) Chr 20: 63.4 – 63.47 Mb Chr 2: 180.72 – 180.78 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

K_v7.2 (KvLQT2) is a voltage- and lipid-gated potassium channel protein coded for by the gene KCNQ2.

Mutations in the KCNQ2 gene are dominant autosomally inherited causes of benign familial neonatal epilepsy. ^[5]

Function

The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene. ^[6]

Ligands

ICA-069673

Compound #40 (Amato 2011)

• ICA-069673: channel opener at KCNQ2/Q3, 20-fold selective over KCNQ3/Q5, no measurable activity against a panel of cardiac ion channels (hERG, Nav1.5, L type channels, and KCNQ1) and no activity on GABA_A gated channels at 10 μM. A range of related benzamides exhibited activity, of which compound number 40 is shown here. ^[7]
• ML252: channel inhibitor, IC₅₀ = 70nM. ^[8]
• Phosphatidylinositol 4,5-bisphosphate (PIP₂)

See also

• KCNQ2 developmental and epileptic encephalopathy

References

1. ENSG00000281151 GRCh38: Ensembl release 89: ENSG00000075043, ENSG00000281151 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000016346 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Miceli F, Soldovieri MV, Weckhuysen S, Cooper E, Taglialatela M (1993). "KCNQ2-Related Disorders". In Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A (eds.). GeneReviews. University of Washington, Seattle. PMID   20437616 . Retrieved 8 September 2024– via National Library of Medicine.
6. "Entrez Gene: KCNQ2 potassium voltage-gated channel, KQT-like subfamily, member 2".
7. Amato G (2011). "N -Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy". ACS Medicinal Chemistry Letters. 2 (6): 481–484. doi:10.1021/ml200053x. PMC   4018159 . PMID   24900334.
8. Cheung YY, Yu H, Xu K, Zou B, Wu M, McManus OB, et al. (August 2012). "Discovery of a series of 2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as novel molecular switches that modulate modes of K(v)7.2 (KCNQ2) channel pharmacology: identification of (S)-2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)butanamide (ML252) as a potent, brain penetrant K(v)7.2 channel inhibitor". Journal of Medicinal Chemistry. 55 (15): 6975–9. doi:10.1021/jm300700v. PMC   3530927 . PMID   22793372.

Further reading

• Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, et al. (December 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacological Reviews. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID   16382104. S2CID   219195192.
• Yokoyama M, Nishi Y, Yoshii J, Okubo K, Matsubara K (October 1996). "Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles". DNA Research. 3 (5): 311–20. doi: 10.1093/dnares/3.5.311 . PMID   9039501.
• Singh NA, Charlier C, Stauffer D, DuPont BR, Leach RJ, Melis R, et al. (January 1998). "A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns". Nature Genetics. 18 (1): 25–9. doi:10.1038/ng0198-25. PMID   9425895. S2CID   30469895.
• Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, et al. (January 1998). "A potassium channel mutation in neonatal human epilepsy". Science. 279 (5349): 403–6. Bibcode:1998Sci...279..403B. doi:10.1126/science.279.5349.403. PMID   9430594.
• Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, et al. (July 1998). "Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy". The Journal of Biological Chemistry. 273 (31): 19419–23. doi: 10.1074/jbc.273.31.19419 . PMID   9677360.
• Tinel N, Lauritzen I, Chouabe C, Lazdunski M, Borsotto M (November 1998). "The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3". FEBS Letters. 438 (3): 171–6. Bibcode:1998FEBSL.438..171T. doi:10.1016/S0014-5793(98)01296-4. PMID   9827540. S2CID   33708352.
• Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, et al. (December 1998). "KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel". Science. 282 (5395): 1890–3. Bibcode:1998Sci...282.1890W. doi:10.1126/science.282.5395.1890. PMID   9836639.
• Schroeder BC, Kubisch C, Stein V, Jentsch TJ (December 1998). "Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy". Nature. 396 (6712): 687–90. Bibcode:1998Natur.396..687S. doi:10.1038/25367. PMID   9872318. S2CID   4417442.
• Biervert C, Steinlein OK (March 1999). "Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions". Human Genetics. 104 (3): 234–40. doi:10.1007/PL00008713. PMID   10323247. S2CID   30751027.
• Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Delmas P, Buckley NJ, et al. (September 1999). "Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell" (PDF). The Journal of Neuroscience. 19 (18): 7742–56. doi:10.1523/jneurosci.19-18-07742.1999. PMC   6782456 . PMID   10479678.
• Shapiro MS, Roche JP, Kaftan EJ, Cruzblanca H, Mackie K, Hille B (March 2000). "Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current". The Journal of Neuroscience. 20 (5): 1710–21. doi: 10.1523/jneurosci.20-05-01710.2000 . PMC   6772928 . PMID   10684873.
• Rundfeldt C, Netzer R (March 2000). "The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits". Neuroscience Letters. 282 (1–2): 73–6. doi:10.1016/S0304-3940(00)00866-1. PMID   10713399. S2CID   28431577.
• Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Jentsch TJ, Brown DA (February 2000). "Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors". The Journal of Physiology. 522 (3): 349–55. doi:10.1111/j.1469-7793.2000.t01-2-00349.x. PMC   2269765 . PMID   10713961.
• Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, et al. (April 2000). "Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy". Proceedings of the National Academy of Sciences of the United States of America. 97 (9): 4914–9. Bibcode:2000PNAS...97.4914C. doi: 10.1073/pnas.090092797 . PMC   18332 . PMID   10781098.
• Schwake M, Pusch M, Kharkovets T, Jentsch TJ (May 2000). "Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy". The Journal of Biological Chemistry. 275 (18): 13343–8. doi: 10.1074/jbc.275.18.13343 . PMID   10788442.
• Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA (August 2000). "Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine". Molecular Pharmacology. 58 (2): 253–62. doi:10.1124/mol.58.2.253. PMID   10908292. S2CID   11112809.
• Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK (September 2000). "Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels". Molecular Pharmacology. 58 (3): 591–600. doi:10.1124/mol.58.3.591. PMID   10953053.
• Tinel N, Diochot S, Lauritzen I, Barhanin J, Lazdunski M, Borsotto M (September 2000). "M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit". FEBS Letters. 480 (2–3): 137–41. Bibcode:2000FEBSL.480..137T. doi: 10.1016/S0014-5793(00)01918-9 . PMID   11034315. S2CID   8386123.
• Smith JS, Iannotti CA, Dargis P, Christian EP, Aiyar J (February 2001). "Differential expression of kcnq2 splice variants: implications to m current function during neuronal development". The Journal of Neuroscience. 21 (4): 1096–103. doi: 10.1523/jneurosci.21-04-01096.2001 . PMC   6762257 . PMID   11160379.
• Miraglia del Giudice E, Coppola G, Scuccimarra G, Cirillo G, Bellini G, Pascotto A (December 2000). "Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor". European Journal of Human Genetics. 8 (12): 994–7. doi: 10.1038/sj.ejhg.5200570 . PMID   11175290.

External links

• KCNQ2+Potassium+Channel at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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