KCNH1 (potassium voltage-gated channel, subfamily H (eag-related), member 1)

2008-01-01 Luis A Pardo Affiliation

Max-Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany

Identity

HGNC

KCNH1

LOCATION

1q32.2

LOCUSID

3756

ALIAS

EAG,EAG1,Kv10.1,TMBTS,ZLS1,h-eag,hEAG,hEAG1

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

450 Kb, 11 exons.

Transcription

Main RNA species with 9Kb. An alternatively spliced variant with 81 additional bp.

Proteins

Description

Tetramer consisting of subunits with 969 aminoacids each. The protein contains a PAS domain at the N-terminus, "Channel" domain with typical features of K channels (six putatively transmembrane segments and a pore loop between fifth and sixth). Large C-terminal domain with cyclic-nucleotide-binding domain, calmodulin binding site, tetramerizing coiled-coil. The sequence has many potential posttranslational modification sites, but only glycosylation has been reported.

Expression

Abundant in many brain regions, virtually absent from extracranial tissues. Detected in gastric gland chief cells, pancreatic acini, spermatogenic cells, endocervix, secretory endometrium, reactive lymph nodes (germinal centre), mast cells, macrophages, anterior pituitary, adrenal gland.

Localisation

Plasma membrane. Abundant in intracellular pools both in neurons and tumor cells.

Function

Voltage-gated potassium channel.

Homology

Homologous to the "six-transmembrane, one pore" potassium channel superfamily.

Implicated in

Entity name

Sarcomas (71% positivity).

Disease

Fibrosarcoma, leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, synovial sarcoma.

Prognosis

Indicative of worse outcome in liposarcoma.

Entity name

Solid epithelial tumors (70% positivity).

Disease

Esophageal, gastric, colon, hepatocellular, gallbladder, pancreatic, renal cell, transitional, prostate, cervical, endometrial, breast and bronchus carcinoma ; cystadenocarcinoma of the ovary, thyroid papillary carcinoma, basalioma, spinalioma, malignant melanoma.

Bibliography

Pubmed ID	Last Year	Title	Authors
11426295	2001	Physiology of EAG K+ channels.	Bauer CK et al
9763622	1998	An ether -à-go-go K+ current, Ih-eag, contributes to the hyperpolarization of human fusion-competent myoblasts.	Bijlenga P et al
17451210	2007	Aberrant expression of ether à go-go potassium channel in colorectal cancer patients and cell lines.	Ding XW et al
15466192	2004	Ether a go-go potassium channels as human cervical cancer markers.	Farias LM et al
17671204	2007	Monoclonal antibody blockade of the human Eag1 potassium channel function exerts antitumor activity.	Gómez-Varela D et al
12172639	2002	Effects of imipramine on ion channels and proliferation of IGR1 melanoma cells.	Gavrilova-Ruch O et al
17022810	2006	Overexpression of Eag1 potassium channels in clinical tumours.	Hemmerlein B et al
12554641	2003	C-terminal domains implicated in the functional surface expression of potassium channels.	Jenke M et al
9400421	1997	Carboxy-terminal domain mediates assembly of the voltage-gated rat ether-à-go-go potassium channel.	Ludwig J et al
7925287	1994	Functional expression of a rat homologue of the voltage gated either á go-go potassium channel reveals differences in selectivity and activation kinetics between the Drosophila channel and its mammalian counterpart.	Ludwig J et al
17022811	2006	Ether à go-go potassium channel expression in soft tissue sarcoma patients.	Mello de Queiroz F et al
15964838	2005	Glycosylation of Eag1 (Kv10.1) potassium channels: intracellular trafficking and functional consequences.	Napp J et al
9738473	1998	Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion.	Occhiodoro T et al
11697078	2001	Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether.a-gogo K+ channel.	Ouadid-Ahidouch H et al
9813096	1998	Cell cycle-related changes in the conducting properties of r-eag K+ channels.	Pardo LA et al
10523298	1999	Oncogenic potential of EAG K(+) channels.	Pardo LA et al
15364405	2004	Expression of ether à go-go potassium channels in human gliomas.	Patt S et al
10880439	2000	Inhibition of human ether à go-go potassium channels by Ca(2+)/calmodulin.	Schönherr R et al
17135369	2007	Voltage-gated K+ channels support proliferation of colonic carcinoma cells.	Spitzner M et al
1840699	1991	A distinct potassium channel polypeptide encoded by the Drosophila eag locus.	Warmke J et al
16537547	2006	Silencing the activity and proliferative properties of the human EagI Potassium Channel by RNA Interference.	Weber C et al
16478480	2006	Inhibition of human ether à go-go potassium channels by Ca2+/calmodulin binding to the cytosolic N- and C-termini.	Ziechner U et al

Other Information

Locus ID:

NCBI: 3756
MIM: 603305
HGNC: 6250
Ensembl: ENSG00000143473

Variants:

dbSNP: 3756
ClinVar: 3756
TCGA: ENSG00000143473
COSMIC: KCNH1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000143473	ENST00000271751	O95259
ENSG00000143473	ENST00000367007	A0A1X7SBS6
ENSG00000143473	ENST00000638357	A0A1W2PRZ5
ENSG00000143473	ENST00000638498	A0A1W2PNI2
ENSG00000143473	ENST00000638960	O95259
ENSG00000143473	ENST00000639952	O95259
ENSG00000143473	ENST00000640044	A0A1W2PPA2
ENSG00000143473	ENST00000640243	A0A1W2PRV9
ENSG00000143473	ENST00000640522	A0A1W2PP68
ENSG00000143473	ENST00000640528	O95259
ENSG00000143473	ENST00000640566	A0A0S1TJ81
ENSG00000143473	ENST00000640625	A0A1W2PRD8
ENSG00000143473	ENST00000640710	O95259

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Neuronal System	REACTOME	R-HSA-112316
Potassium Channels	REACTOME	R-HSA-1296071
Voltage gated Potassium channels	REACTOME	R-HSA-1296072

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
24336491	2014	The roles of K(+) channels in cancer.	126
17360457	2007	KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging.	114
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
18927085	2008	Eag1 expression interferes with hypoxia homeostasis and induces angiogenesis in tumors.	56
16537547	2006	Silencing the activity and proliferative properties of the human EagI Potassium Channel by RNA Interference.	45
20201926	2010	Human variation in alcohol response is influenced by variation in neuronal signaling genes.	45
25915598	2015	Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome.	45
15548764	2005	Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel.	44
17022811	2006	Ether à go-go potassium channel expression in soft tissue sarcoma patients.	40
25420144	2015	Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy.	37

Citation

Luis A Pardo

KCNH1 (potassium voltage-gated channel, subfamily H (eag-related), member 1)

Atlas Genet Cytogenet Oncol Haematol. 2008-01-01

Online version: http://atlasgeneticsoncology.org/gene/41048/kcnh1