Description: potassium voltage-gated channel, subfamily H (eag-related), member 3
Gene: Kcnh3     Synonyms: Kv12.2

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Kv12.2, also known as ether-a-go-go-like 2 (Elk2) or KCNH3, belongs to the ether-a-go-go (EAG) family, which comprises the ether-a-go-go (Eag, Kv10.x), ether-a-go-go-related gene (Erg, Kv11.x), and ether-a-go-go like (Elk, Kv12.x) subfamilies [812], [778]. Unlike Kv5.x, Kv6.x, Kv8.x, and Kv9.x, which function as modifiers for other Kv channels [606], Kv12.2 can produce a functional channel on its own when heterologously expressed [809], [808], [813]. (From [802])

Kv12.2 is potassium voltage-gated channel subfamily H member 3, a protein that in humans is encoded by the KCNH3 gene [606], [810]. It is also known as BEC1; ELK2; Kv12.2; KIAA1282.

Experimental data



RGD ID Chromosome Position Species
71070 7 137984618-138002553 Rat
736943 15 99055407-99073248 Mouse
733984 12 49932940-49952077 Human

Kcnh3 : potassium voltage-gated channel, subfamily H (eag-related), member 3



Acc No Sequence Length Source
NM_017108 n/A n/A NCBI
NM_010601 n/A n/A NCBI
NM_012284 n/A n/A NCBI



Accession Name Definition Evidence
GO:0016020 membrane Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins. IEA
GO:0016021 integral to membrane Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane. IEA

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Glycosylation in CHO Cells

N-glycosylation effects the function of Kv12.2, inasmuch as that removal of sugar chains causes a depolarizing shift in the steady-state activation without a significant reduction in current amplitude. Unlike the previously reported shift for Shaker-type Kv channels, this shift does not appear to be due to negatively charged sialic acid residues in the sugar chains. Kv12.2 is N-glycosylated in Chinese hamster ovary (CHO) cells and in cultured neurons as well as in the mouse brain. Only glycosylated Kv12.2 channels show proper voltage dependence and are utilized in vivo. [802]


KCNE1 and KCNE3 beta-subunits regulate membrane surface expression of kv12.2 channels in vitro and form tripartite complex in vivo [801]


RELK1 and RELK2 currents were not blocked by 10 μm E4031 (n = 5), which blocks HERG channels, nor by 10 μm linopirdine (n = 5), which blocks M-channels [809]



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There is a light oxygen voltage (LOV) and cyclic nucleotide binding (CNB) domain in the N and C terminus, respectively. [606]

Kv12.2 features the longest S5-P loop among all known mammalian Kv channels with the most N-linked glycosylation sites (three sites). [802]





Kv12.2 was found in infant brain, lung (small cell carcinoma), eye (retinoblastoma), sciatic nerve, cortex, amygdala, hippocampus (mainly in CA1 and CA3 pyramidal cell body layers and in the granule cell layers of the dentate gyrus); in the striatal regions, including the putamen and caudate nucleus, lymphocytes, leukemias, and NG108-15 cell line. [327], [793], [810], [809], [811]. (Summary from [606])

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In addition, human Kv12.2 may be implicated in epilepsy [814].


ELK2 channels are very effective at dampening the neuronal excitability, but less so at producing adaptation of action potential firing frequency. In addition, we suggest experimental ways to recognize HELK2 currents in vivo and raise the issue of the possible function of these channels in astrocytoma [813]

Hyppocampal Hyperexcitability and Epilepsy

We show here that the voltage-gated K+ channel Kv12.2 is a potent regulator of excitability in hippocampal pyramidal neurons. Genetic deletion and pharmacologic block of Kv12.2 significantly reduced firing threshold in these neurons. Kv12.2−/− mice displayed signs of persistent neuronal hyperexcitability including frequent interictal spiking, spontaneous seizures and increased sensitivity to the chemoconvulsant pentylenetetrazol [803]

Cognitive Function

Disruption of the Ether-à-go-go K+ Channel Gene Kv12.2/KCNH3 Enhances Cognitive Function [1786]

Transcription of KCNH3

The transcription of KCNH3 the gene coding for Kv12.2 may be activated by the transcription factor FOXG1 in mature neurons of the CNS suggesting a possible link to the FOXG1 syndrome pathology [2086]

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Rat Kv12.2 channels very similar to HERG

RELK2 channels gave rise to slowly activating K+ currents. At more positive potentials, the evoked currents inactivated rapidly. Recovery from inactivation at negative potentials was reminiscent of that seen for HERG channels [809]

Mouse Kv12.2 in CHO cells display Current with EGFP

Kv.11.1 Here we present the evidence that Kv12.2 channels are expressed and N-glycosylated in the mouse brain and that N-glycosylation is essential for proper function of EGFP-Kv12.2 expressed in Chinese hamster ovary (CHO) cells. Furthermore, by a systematic mutational analysis of the three glycosylation sites of Kv12.2, our study provides insight into how glycosylation regulates the trafficking of Kv channels. To improve the reproducibility of our measurements, we fused EGFP to the N terminus of Kv12.2. When cells were transfected with EGFP-Kv12.2, almost all EGFP-positive cells showed voltage-dependent transient outward currents and characteristic tail currents, which were absent in mock-transfected cells. The currents were similar to those of untagged Kv12.2 channels which were previously reported. We, therefore, concluded that EGFP-Kv12.2 could be used for further characterization of the channel [802] For other scenarios in CHO cells EGFP was also used [809]

pH sensitivity of Kv12.1,Kv12.2 and Kv12.3

Kv.12.2 Whole cell patch clamp recordings made on HEK293 cells transfected with Elk channels hKv12.1, hKv12.2, and hKv12.3 demonstrated that external acidification inhibits their activation. High sensitivity to physiological changes in pH may be a general feature of the EAG superfamily of K+ channels as it was also observed for Kv10.1 and Kv11.1.[1832]





Miyake A et al. New ether-à-go-go K(+) channel family members localized in human telencephalon.
J. Biol. Chem., 1999 Aug 27 , 274 (25018-25).


Meves H et al. Separation of M-like current and ERG current in NG108-15 cells.
Br. J. Pharmacol., 1999 Jul , 127 (1213-23).


Smith GA et al. Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells.
J. Biol. Chem., 2002 May 24 , 277 (18528-34).


Ganetzky B et al. The eag family of K+ channels in Drosophila and mammals.
Ann. N. Y. Acad. Sci., 1999 Apr 30 , 868 (356-69).


Bauer CK et al. Physiology of EAG K+ channels.
J. Membr. Biol., 2001 Jul 1 , 182 (1-15).


Engeland B et al. Cloning and functional expression of rat ether-à-go-go-like K+ channel genes.
J. Physiol. (Lond.), 1998 Dec 15 , 513 ( Pt 3) (647-54).


Zou A et al. Distribution and functional properties of human KCNH8 (Elk1) potassium channels.
Am. J. Physiol., Cell Physiol., 2003 Dec , 285 (C1356-66).


Becchetti A et al. The functional properties of the human ether-à-go-go-like (HELK2) K+ channel.
Eur. J. Neurosci., 2002 Aug , 16 (415-28).

Miyake A et al. Disruption of the ether-a-go-go K+ channel gene BEC1/KCNH3 enhances cognitive function.
J. Neurosci., 2009 Nov 18 , 29 (14637-45).



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