KCNH1

Protein-coding gene in the species Homo sapiens

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]
Band	1q32.2	End	211,134,165 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 1 (mouse)^[2]

Band	1\|1 H6	Start	191,873,082 bp^[2]
Band	1\|1 H6	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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000143473 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000058248 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ ^a ^b "Entrez Gene: KCNH1 potassium voltage-gated channel, subfamily H (eag-related), member 1".
^ 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.
^ "603305 - Potassium channel, voltage-gated; subfamily H, member 1; KCNH1". Online Mendelian Inheritance in Man (OMIM).
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

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

Classification	D OMIM: 603305

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

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3
Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ
Proton-gated	Amiloride-sensitive cation channel 1 2 3 4
Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺: Proton channel	HVCN1
M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm: Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin