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Gene Review

KCNE4  -  potassium channel, voltage gated subfamily...

Homo sapiens

Synonyms: MiRP3, MinK-related peptide 3, Minimum potassium ion channel-related peptide 3, Potassium channel subunit beta MiRP3, Potassium voltage-gated channel subfamily E member 4
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High impact information on KCNE4

  • Compared to non-failing tissue, failing hearts showed higher expression of Kv4.3-L and KCNE1 and lower of Kv4.3-S, KChIP2, KCNE4, and KCNE5 [1].
  • Having the broad distribution of Kv1 channels in mind, the demonstrated inhibitory property of KCNE4-subunits could locally and/or transiently have a dramatic influence on cellular excitability and on setting resting membrane potentials [2].
  • Co-expression of KCNQ1 and KCNE4 in Xenopus oocytes completely inhibited the KCNQ1 current [3].
  • This notion was supported by immunocytochemical studies and Western blotting, showing no significant difference in plasma membrane expression of KCNQ1 channels in the presence or absence of KCNE4 [3].
  • RT-PCR studies revealed high KCNE4 expression in embryos and adult uterus, where significant expression of KCNQ1 channels has also been demonstrated [3].

Biological context of KCNE4

  • Recently, this finding has been challenged by Teng et al., stating that the human variant of KCNE4 does not attenuate the KCNQ1 current but does slightly modulate the activation kinetics of the channel after expression in Xenopus laevis oocytes [Biochem. Biophys. Res. Commun. 303 (2003) 808] [4].
  • The hKCNE4 gene encodes 170 amino acid protein and is localized to chromosome 2q35-36 [5].

Anatomical context of KCNE4


Regulatory relationships of KCNE4

  • We have previously published that the murine variant of KCNE4 inhibits the human KCNQ1 current [J. Physiol. 542 (2002) 119] [4].

Other interactions of KCNE4

  • In the present study, a detailed investigation on the ability of human and murine KCNE4 to affect either human or murine KCNQ1 currents has been performed [4].
  • The protein sequence shows 90% homology to mouse KCNE4 and 38% identity to human KCNE1 [5].
  • No mutation was found in three plausibly candidate genes: the KCNE4 gene, the TUBA1 gene and a predicted gene located in genomic contig NT_005403 [6].


  1. Functional modulation of the transient outward current Ito by KCNE beta-subunits and regional distribution in human non-failing and failing hearts. Radicke, S., Cotella, D., Graf, E.M., Banse, U., Jost, N., Varró, A., Tseng, G.N., Ravens, U., Wettwer, E. Cardiovasc. Res. (2006) [Pubmed]
  2. KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels. Grunnet, M., Rasmussen, H.B., Hay-Schmidt, A., Rosenstierne, M., Klaerke, D.A., Olesen, S.P., Jespersen, T. Biophys. J. (2003) [Pubmed]
  3. KCNE4 is an inhibitory subunit to the KCNQ1 channel. Grunnet, M., Jespersen, T., Rasmussen, H.B., Ljungstrøm, T., Jorgensen, N.K., Olesen, S.P., Klaerke, D.A. J. Physiol. (Lond.) (2002) [Pubmed]
  4. hKCNE4 inhibits the hKCNQ1 potassium current without affecting the activation kinetics. Grunnet, M., Olesen, S.P., Klaerke, D.A., Jespersen, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  5. Novel gene hKCNE4 slows the activation of the KCNQ1 channel. Teng, S., Ma, L., Zhen, Y., Lin, C., Bähring, R., Vardanyan, V., Pongs, O., Hui, R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  6. A second locus mapping to 2q35-36 for familial pseudohyperkalaemia. Carella, M., d'Adamo, A.P., Grootenboer-Mignot, S., Vantyghem, M.C., Esposito, L., D'Eustacchio, A., Ficarella, R., Stewart, G.W., Gasparini, P., Delaunay, J., Iolascon, A. Eur. J. Hum. Genet. (2004) [Pubmed]
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