KCNH1

KCNH1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKCNH1, EAG, EAG1, Kv10.1, h-eag, TMBTS, ZLS1, hEAG1, potassium voltage-gated channel subfamily H member 1, hEAG
External IDsOMIM: 603305 MGI: 1341721 HomoloGene: 68242 GeneCards: KCNH1
Orthologs
SpeciesHumanMouse
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 MbChr 1: 191.87 – 192.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000143473 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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

External links

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