KCNH1

KCNH1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5J7E
Identifiers
Aliases	KCNH1 , EAG, EAG1, Kv10.1, h-eag, TMBTS, ZLS1, hEAG1, potassium voltage-gated channel subfamily H member 1, hEAG
External IDs	OMIM: 603305 MGI: 1341721 HomoloGene: 68242 GeneCards: KCNH1
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1q32.2 Start 210,676,823 bp [1] End 211,134,165 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1|1 H6 Start 191,873,082 bp [2] End 192,192,467 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 9 prefrontal cortex cerebellar hemisphere cingulate gyrus caudate nucleus stromal cell of endometrium putamen nucleus accumbens islet of Langerhans corpus callosum Top expressed in secondary oocyte olfactory tubercle primary motor cortex nucleus accumbens molar superior frontal gyrus supraoptic nucleus choroid plexus prefrontal cortex visual cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphorelay sensor kinase activity voltage-gated potassium channel activity calmodulin binding cyclic nucleotide binding ion channel activity potassium channel activity voltage-gated ion channel activity protein binding lipid binding phosphatidylinositol bisphosphate binding delayed rectifier potassium channel activity identical protein binding protein kinase binding transmembrane transporter binding protein heterodimerization activity 14-3-3 protein binding Cellular component synapse integral component of membrane nucleus axon nuclear inner membrane presynaptic membrane membrane early endosome membrane dendrite plasma membrane endosome voltage-gated potassium channel complex postsynaptic density cell junction cell projection perikaryon intracellular membrane-bounded organelle postsynaptic membrane integral component of plasma membrane cell surface axolemma potassium channel complex neuronal cell body perinuclear region of cytoplasm integral component of presynaptic membrane Biological process transmembrane transport regulation of cell population proliferation potassium ion transport signal transduction phosphorelay signal transduction system regulation of ion transmembrane transport ion transport potassium ion transmembrane transport myoblast fusion regulation of membrane potential phosphatidylinositol-mediated signaling startle response ion transmembrane transport cellular response to calcium ion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3756 16510 Ensembl ENSG00000143473 ENSMUSG00000058248 UniProt O95259 Q60603 RefSeq (mRNA) NM_002238 NM_172362 NM_001038607 NM_010600 RefSeq (protein) NP_002229 NP_758872 NP_001033696 NP_034730 Location (UCSC) Chr 1: 210.68 – 211.13 Mb Chr 1: 191.87 – 192.19 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Potassium voltage-gated channel subfamily H member 1 is a protein that in humans is encoded by the KCNH1 gene. ^{[5] [6] [7]}

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms. ^[7]

Interactions

KCNH1 has been shown to interact with KCNB1. ^[8]

Function

The KCNH1 gene encodes a highly conserved voltage-gated potassium channel with predominant expression in the adult central nervous system. ^[9]

Pathologies

Gabbett and colleagues described Temple–Baraitser syndrome (TBS) in 2008, naming the condition after English clinical geneticists Profs Karen Temple and Michael Baraitser. ^[10] They then went on to demonstrate that de novo missense mutations in the KCNH1 gene cause deleterious gain of function in the voltage-gated potassium channel, resulting in the multisystem developmental disorder. TBS is categorized by intellectual disabilities, epilepsy, typical facial features, and aplasia of the nails. Simons et al. demonstrated that mutational mosaicism present in the mothers of some probands was responsible for their children's TBS phenotype. This is further evidence of the role that genetic mosaicism plays in the etiology of neurological disorders. ^[11]

Type 1 Zimmermann–Laband syndrome was later found to be caused by similar mutations in KCNH1. ^[12] This has led some researchers to believe that type 1 Zimmermann-Laband and Temple-Baraitser syndromes are different manifestations of the same disorder. ^{[13] [14]}

See also

• Voltage-gated potassium channel

References

1. GRCh38: Ensembl release 89: ENSG00000143473 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000058248 - 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. Occhiodoro T, Bernheim L, Liu JH, Bijlenga P, Sinnreich M, Bader CR, Fischer-Lougheed J (August 1998). "Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion". FEBS Letters. 434 (1–2): 177–182. doi: 10.1016/S0014-5793(98)00973-9 . PMID   9738473.
6. 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.
7. "Entrez Gene: KCNH1 potassium voltage-gated channel, subfamily H (eag-related), member 1".
8. Ottschytsch N, Raes A, Van Hoorick D, Snyders DJ (June 2002). "Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome". Proceedings of the National Academy of Sciences of the United States of America. 99 (12): 7986–7991. Bibcode:2002PNAS...99.7986O. doi: 10.1073/pnas.122617999 . PMC   123007 . PMID   12060745.
9. "603305 - Potassium channel, voltage-gated; subfamily H, member 1; KCNH1". Online Mendelian Inheritance in Man (OMIM).
10. Gabbett MT, Clark RC, McGaughran JM (February 2008). "A second case of severe mental retardation and absent nails of hallux and pollex (Temple-Baraitser syndrome)". American Journal of Medical Genetics. Part A. 146A (4): 450–452. doi:10.1002/ajmg.a.32129. PMID   18203178. S2CID   2532859.
11. Simons C, Rash LD, Crawford J, Ma L, Cristofori-Armstrong B, Miller D, et al. (January 2015). "Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy". Nature Genetics. 47 (1): 73–77. doi:10.1038/ng.3153. PMID   25420144. S2CID   52799681.
12. Kortüm F, Caputo V, Bauer CK, Stella L, Ciolfi A, Alawi M, et al. (June 2015). "Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome". Nature Genetics. 47 (6): 661–667. doi:10.1038/ng.3282. hdl: 2108/118197 . PMID   25915598. S2CID   12060592.
13. Mégarbané A, Al-Ali R, Choucair N, Lek M, Wang E, Ladjimi M, et al. (June 2016). "Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome: one clinical entity?". BMC Medical Genetics. 17 (1): 42. doi: 10.1186/s12881-016-0304-4 . PMC   4901505 . PMID   27282200.
14. Bramswig NC, Ockeloen CW, Czeschik JC, van Essen AJ, Pfundt R, Smeitink J, et al. (October 2015). "'Splitting versus lumping': Temple-Baraitser and Zimmermann-Laband Syndromes". Human Genetics. 134 (10): 1089–1097. doi:10.1007/s00439-015-1590-1. PMID   26264464. S2CID   14238362.

Further reading

• Warmke JW, Ganetzky B (April 1994). "A family of potassium channel genes related to eag in Drosophila and mammals". Proceedings of the National Academy of Sciences of the United States of America. 91 (8): 3438–3442. Bibcode:1994PNAS...91.3438W. doi: 10.1073/pnas.91.8.3438 . PMC   43592 . PMID   8159766.
• Hoshi N, Takahashi H, Shahidullah M, Yokoyama S, Higashida H (September 1998). "KCR1, a membrane protein that facilitates functional expression of non-inactivating K+ currents associates with rat EAG voltage-dependent K+ channels". The Journal of Biological Chemistry. 273 (36): 23080–23085. doi: 10.1074/jbc.273.36.23080 . PMID   9722534.
• Pardo LA, del Camino D, Sánchez A, Alves F, Brüggemann A, Beckh S, Stühmer W (October 1999). "Oncogenic potential of EAG K(+) channels". The EMBO Journal. 18 (20): 5540–5547. doi:10.1093/emboj/18.20.5540. PMC   1171622 . PMID   10523298.
• Schönherr R, Löber K, Heinemann SH (July 2000). "Inhibition of human ether à go-go potassium channels by Ca(2+)/calmodulin". The EMBO Journal. 19 (13): 3263–3271. doi:10.1093/emboj/19.13.3263. PMC   313935 . PMID   10880439.
• Cayabyab FS, Schlichter LC (April 2002). "Regulation of an ERG K+ current by Src tyrosine kinase". The Journal of Biological Chemistry. 277 (16): 13673–13681. doi: 10.1074/jbc.M108211200 . PMID   11834728.
• Schönherr R, Gessner G, Löber K, Heinemann SH (March 2002). "Functional distinction of human EAG1 and EAG2 potassium channels". FEBS Letters. 514 (2–3): 204–208. doi:10.1016/S0014-5793(02)02365-7. PMID   11943152. S2CID   8404036.
• Ottschytsch N, Raes A, Van Hoorick D, Snyders DJ (June 2002). "Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome". Proceedings of the National Academy of Sciences of the United States of America. 99 (12): 7986–7991. Bibcode:2002PNAS...99.7986O. doi: 10.1073/pnas.122617999 . PMC   123007 . PMID   12060745.
• Farias LM, Ocaña DB, Díaz L, Larrea F, Avila-Chávez E, Cadena A, et al. (October 2004). "Ether a go-go potassium channels as human cervical cancer markers". Cancer Research. 64 (19): 6996–7001. doi:10.1158/0008-5472.CAN-04-1204. PMID   15466192. S2CID   6791131.
• Kang J, Chen XL, Wang H, Ji J, Cheng H, Incardona J, et al. (March 2005). "Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel". Molecular Pharmacology. 67 (3): 827–836. doi:10.1124/mol.104.006577. PMID   15548764. S2CID   35049797.
• Ziechner U, Schönherr R, Born AK, Gavrilova-Ruch O, Glaser RW, Malesevic M, et al. (March 2006). "Inhibition of human ether à go-go potassium channels by Ca2+/calmodulin binding to the cytosolic N- and C-termini". The FEBS Journal. 273 (5): 1074–1086. doi:10.1111/j.1742-4658.2006.05134.x. PMID   16478480. S2CID   26926041.
• Weber C, de Queiroz FM, Downie BR, Suckow A, Stühmer W, Pardo LA (May 2006). "Silencing the activity and proliferative properties of the human EagI Potassium Channel by RNA Interference". The Journal of Biological Chemistry. 281 (19): 13030–13037. doi: 10.1074/jbc.M600883200 . PMID   16537547.
• Mello de Queiroz F, Suarez-Kurtz G, Stühmer W, Pardo LA (October 2006). "Ether à go-go potassium channel expression in soft tissue sarcoma patients". Molecular Cancer. 5: 42. doi: 10.1186/1476-4598-5-42 . PMC   1618397 . PMID   17022811.
• Ocorr K, Reeves NL, Wessells RJ, Fink M, Chen HS, Akasaka T, et al. (March 2007). "KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging". Proceedings of the National Academy of Sciences of the United States of America. 104 (10): 3943–3948. Bibcode:2007PNAS..104.3943O. doi: 10.1073/pnas.0609278104 . PMC   1820688 . PMID   17360457.
• Ding XW, Yan JJ, An P, Lü P, Luo HS (February 2007). "Aberrant expression of ether à go-go potassium channel in colorectal cancer patients and cell lines". World Journal of Gastroenterology. 13 (8): 1257–1261. doi: 10.3748/wjg.v13.i8.1257 . PMC   4147004 . PMID   17451210.
• Borowiec AS, Hague F, Harir N, Guénin S, Guerineau F, Gouilleux F, et al. (September 2007). "IGF-1 activates hEAG K(+) channels through an Akt-dependent signaling pathway in breast cancer cells: role in cell proliferation" (PDF). Journal of Cellular Physiology. 212 (3): 690–701. doi:10.1002/jcp.21065. PMID   17520698. S2CID   39833770.
• Simons C, Rash LD, Crawford J, Ma L, Cristofori-Armstrong B, Miller D, et al. (January 2015). "Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy". Nature Genetics. 47 (1): 73–77. doi:10.1038/ng.3153. PMID   25420144. S2CID   52799681.

External links

• KCNH1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Kv10.1+Potassium+Channel at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human Disease Genes - KCNH1

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