KCNH1 Membrane Protein Introduction

Introduction of KCNH1

KCNH1, also known as H-Eag, HEAG1, EAG1, EAG, TMBTS, ZLS1, Ether-a-go-go, Drosophila, homolog of KV10.1, or potassium channel, voltage-gated Eag related subfamily H, member 1, is a transmembrane protein of 111.4 k Da and comprises 678 amino acids. In humans, it is encoded by the KCNH1 gene which is located on the chromosome 1q32.2. KCNH1 was originally termed ether à go-go (Eag) as its mutation in Drosophila melanogaster induced a rhythmic leg-shaking phenotype under ether anesthesia. This protein is expressed in different regions of central nervous systems, such as the hippocampus. KCNH1 contains tetrameric α subunits and each subunit consists of 6 membrane-spanning α-helices (S1-S6), of which S1-S4 segments work as voltage sensor domains, and S5, S6 form a pore-lining loop.

Basic Information of KCNH1
Protein Name Potassium voltage-gated channel subfamily H member 1
Gene Name KCNH1
Aliases Ether-a-go-go potassium channel 1, EAG channel 1, h-eag, hEAG1, Voltage-gated potassium channel subunit Kv10.1
Organism Homo sapiens (Human)
UniProt ID O95259
Transmembrane Times 6
Length (aa) 989

Function of KCNH1 Membrane Protein

KCNH1, as voltage-gated potassium (Kv) channel, has the canonical tetrameric structure and six-transmembrane domain topology. In humans, at least 12 (Kv) subfamilies (Kv1 to Kv12) contribute to neuronal signaling in nervous systems. In mammals, the expression of KCNH1 is almost completely limited to the brain, but no specific neuronal function yet is described. Thus far, the only physiological effect ascribed to the vertebrate KCNH1 channel is a promoting role at the onset of myoblast fusion. KCNH channels are essential regulators of cellular excitability and reported to be correlated with cancer, epilepsy, schizophrenia, and cardiac long QT syndrome type 2. An important pathophysiological impact for KCNH1 in the cancer formation has been proposed since the human KCNH1 gene is overexpressed in a broad spectrum of cancers and the channel inhibition can reduce cell proliferation. Additionally, a recent study revealed that missense mutations in KCNH1 cause deleterious gain of function, leading to a multisystem developmental disorder Temple-Baraitser syndrome (TBS).

The membrane topology and domain structure of a single Kcnh1 subunit.Fig.1 The membrane topology and domain structure of a single Kcnh1 subunit. (Stengel, 2012)

Application of KCNH1 Membrane Protein in Literature

  1. Niday Z and Tzingounis A.V. Potassium Channel Gain of Function in Epilepsy: An Unresolved Paradox. Neuroscientist. 2018, 24(4): 368-380. PubMed ID: 29542386

    The article describes the current state of the field in regard of the gain-of-function potassium channel variants related to epilepsy (KCNT1, KCNA2, KCNB1, KCND2, KCNH1, KCNH5, KCNJ10, KCNMA1, KCNQ2, and KCNQ3) and speculated on possible mechanisms behind the development of seizures and epilepsy in patients.

  2. Mastrangelo M., et al. Epilepsy in KCNH1-related syndromes. Epileptic Disord. 2016, 18(2): 123-136. PubMed ID: 27267311

    KCNH1 mutations have been identified in patients with Temple-Baraitser syndrome and Zimmermann-Laband syndrome, and patients with indefinite syndromes with intellectual disability and overlapping characteristics. Epilepsy is a critical phenotypic feature in a large number of individuals with KCNH1-related syndromes, advising a direct role of KCNH1 in epileptogenesis.

  3. Fukai R., et al. De novo KCNH1 mutations in four patients with syndromic developmental delay, hypotonia and seizures. J Hum Genet. 2016, 61(5): 381-387. PubMed ID: 26818738

    De novo missense mutations of KCNH1 have recently been identified in 6 patients with Zimmermann-Laband syndrome and in 4 patients with Temple-Baraitser syndrome. This report confirms that KCNH1 mutations are related to the syndromic neurodevelopmental disorder, and also supported the functional importance of the S4 domain.

  4. Kortüm F., et al. Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome. Nat Genet. 2016, 47(6): 661-667. PubMed ID: 25915598

    Zimmermann-Laband syndrome (ZLS) is a developmental disorder and this study reported that heterozygous missense mutations in KCNH1 are responsible for a considerable proportion of ZLS. The findings indicate that KCNH1 mutations result in ZLS and document genetic heterogeneity for this type of disorder.

  5. Simons C., et al. Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy. Nat Genet. 2015, 47(1): 73-77. PubMed ID: 25420144

    The article discoveries that two mothers of children with Temple-Baraitser syndrome (TBS), who have epilepsy but healthy, are low-level (10% and 27%) mosaic carriers of pathogenic KCNH1 mutations. Consistent with current reports, this result demonstrates that the etiology of lots of unresolved CNS disorders may be explained by pathogenic mosaic mutations.

KCNH1 Preparation Options

To harvest a soluble and natural protein, we have already built mature reconstitution forms and active formats for these membrane proteins. Our efficient Magic™ membrane protein production platform can provide a number of versatile options for all customers, from which they lastly can pick the optimal one to suit their needs. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-KCNH1 antibody development services.

As a seasoned expert in the biotechnological filed, Creative Biolabs has won high reputation from global scientists for successfully accomplished challenging projects. Importantly, we are skilled at offering flexible one-step, customized membrane protein preparation services in required formats. Please feel free to contact us for more information.


  1. Stengel R, et al. (2012). Kcnh1 voltage-gated potassium channels are essential for early zebrafish development. J Biol Chem. 287(42): 35565-35575.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic or any in vivo human use.

Online Inquiry

Verification code
Click image to refresh the verification code.


USA: 45-1 Ramsey Road, Shirley, NY 11967, USA
Europe: Heidenkampsweg 58, 20097 Hamburg, Germany
Call us at:
USA: 1-631-381-2994
Europe: 44-207-097-1828
Fax: 1-631-207-8356
Our customer service representatives are available 24 hours a day, 7 days a week. Contact Us