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Gene Review

KCNE2  -  potassium channel, voltage gated subfamily...

Homo sapiens

Synonyms: ATFB4, LQT5, LQT6, MIRP1, MiRP1, ...
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Disease relevance of KCNE2

  • Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation [1].
  • We identified a novel missense mutation, V65 M, in the KCNE2 gene of a 17-year-old female with syncope and LQTS [2].
  • Mechanisms whereby mutations of KCNE2 produce fatal cardiac arrhythmias characteristic of long-QT syndrome remain unclear [3].
  • Here, we disrupted the murine kcne2 gene and found that kcne2 (-/-) mice have a severe gastric phenotype with profoundly reduced parietal cell proton secretion, abnormal parietal cell morphology, achlorhydria, hypergastrinemia, and striking gastric glandular hyperplasia arising from an increase in the number of non-acid secretory cells [4].
  • A potassium channel protein KCNE2, identified as a down-regulated gene in gastric cancer, was chosen for further study [5].

High impact information on KCNE2


Chemical compound and disease context of KCNE2


Biological context of KCNE2

  • Furthermore, four novel single-nucleotide polymorphisms (SNPs) and one amino acid polymorphism (R1047L) were identified in KCNH2, and one novel SNP and one previously known amino acid polymorphism (T8A) were found in KCNE2 [11].
  • METHODS: We developed a robust single-strand conformation polymorphism-heteroduplex screening analysis, with identical thermocycling conditions for all PCR reactions, covering all of the coding exons in KCNH2 and KCNE2 [11].
  • Identification and functional characterization of a novel KCNE2 (MiRP1) mutation that alters HERG channel kinetics [2].
  • In this study, the frequency of mutations in KCNE2 of 150 unrelated LQTS patients without known genotype and of 100 controls was analyzed using single-strand conformation polymorphism analysis and direct sequencing [2].
  • In this study, we characterize functional interactions between HERG and KCNE2 with a view to defining underlying mechanisms for action potential prolongation and long-QT syndrome [3].

Anatomical context of KCNE2


Associations of KCNE2 with chemical compounds

  • An arginine-to-cysteine mutation at position 27 (R27C) of KCNE2, the beta subunit of the KCNQ1-KCNE2 channel responsible for a background potassium current, was found in 2 of the 28 probands [1].
  • Mutation of arginine to histidine (R --> H) to yield R83H-MiRP2 is associated with periodic paralysis; the analogs K69H-MinK and K75H-MiRP1 were also studied [15].
  • Here, we examine KCNE2 in 98 patients with drug-induced LQTS, identifying three individuals with sporadic mutations and a patient with sulfamethoxazole-associated LQTS who carried a single-nucleotide polymorphism (SNP) found in approximately 1.6% of the general population [16].
  • The KCNQ1/KCNE1/KCNE2 current had a more depolarized activation voltage, a faster deactivation kinetics, and a less sensitivity to activation by mefenamic acid [17].
  • One KCNE2 mutation (R77W) identified in a patient treated with flecainide did not alter I(Kr) [18].

Physical interactions of KCNE2

  • The summation of cAMP-mediated effects is a net diminution of the effective current, but when HERG is complexed with with the K(+) channel accessory proteins MiRP1 or minK, the stimulatory effects of cAMP are favored [19].

Co-localisations of KCNE2


Regulatory relationships of KCNE2

  • In both cell types, co-expressed KCNE2 enhanced HCN4-generated current amplitudes, slowed the activation kinetics and shifted the voltage for half-maximal activation of currents to more negative voltages [12].
  • When HERG was co-expressed with the accessory subunit KCNE2, an IC50 value of 52 microM was determined [21].

Other interactions of KCNE2

  • KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel [8].
  • Missense forme frust mutations were identified in four aLQTS patients: D85N in KCNE1 (two cases), T8A in KCNE2, and P347S in KCNH2 [22].
  • We demonstrate that KCNE2 associates with KCNQ2 and/or KCNQ3 subunits [23].
  • However, the identification of common nonsynonymous single nucleotide polymorphisms (nSNPs; i.e., amino-acid coding variants) with functional phenotypes in the SCN5A Na(+) channel and MiRP1 K(+) channel beta-subunit have challenged this viewpoint [24].
  • No significant EPI-MID differences were observed in the expression of the other channel proteins studied (Kir2.1, alpha1C, HERG and MiRP1) [25].

Analytical, diagnostic and therapeutic context of KCNE2

  • Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) techniques, we studied the reactivity of specific antibodies to the 37-kilodalton (kDa) major iron-regulated protein (MIRP) of gonococci grown under iron-limiting conditions [26].
  • Electroimmunoblotting experiments confirmed that outer-membrane protein III (PIII) and the major iron-regulated protein (MIRP), two conserved gonococcal proteins, were cleaved by cathepsin G [27].


  1. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Yang, Y., Xia, M., Jin, Q., Bendahhou, S., Shi, J., Chen, Y., Liang, B., Lin, J., Liu, Y., Liu, B., Zhou, Q., Zhang, D., Wang, R., Ma, N., Su, X., Niu, K., Pei, Y., Xu, W., Chen, Z., Wan, H., Cui, J., Barhanin, J., Chen, Y. Am. J. Hum. Genet. (2004) [Pubmed]
  2. Identification and functional characterization of a novel KCNE2 (MiRP1) mutation that alters HERG channel kinetics. Isbrandt, D., Friederich, P., Solth, A., Haverkamp, W., Ebneth, A., Borggrefe, M., Funke, H., Sauter, K., Breithardt, G., Pongs, O., Schulze-Bahr, E. J. Mol. Med. (2002) [Pubmed]
  3. Molecular interactions between two long-QT syndrome gene products, HERG and KCNE2, rationalized by in vitro and in silico analysis. Mazhari, R., Greenstein, J.L., Winslow, R.L., Marbán, E., Nuss, H.B. Circ. Res. (2001) [Pubmed]
  4. The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion. Roepke, T.K., Anantharam, A., Kirchhoff, P., Busque, S.M., Young, J.B., Geibel, J.P., Lerner, D.J., Abbott, G.W. J. Biol. Chem. (2006) [Pubmed]
  5. KCNE2, a down-regulated gene identified by in silico analysis, suppressed proliferation of gastric cancer cells. Yanglin, P., Lina, Z., Zhiguo, L., Na, L., Haifeng, J., Guoyun, Z., Jie, L., Jun, W., Tao, L., Li, S., Taidong, Q., Jianhong, W., Daiming, F. Cancer Lett. (2007) [Pubmed]
  6. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Abbott, G.W., Sesti, F., Splawski, I., Buck, M.E., Lehmann, M.H., Timothy, K.W., Keating, M.T., Goldstein, S.A. Cell (1999) [Pubmed]
  7. Long QT syndromes and torsade de pointes. Viskin, S. Lancet (1999) [Pubmed]
  8. KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel. Tinel, N., Diochot, S., Borsotto, M., Lazdunski, M., Barhanin, J. EMBO J. (2000) [Pubmed]
  9. Requirement of subunit expression for cAMP-mediated regulation of a heart potassium channel. Kurokawa, J., Chen, L., Kass, R.S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. Posttranslational control of a cardiac ion channel transgene in vivo: clarithromycin-hMiRP1-Q9E interactions. Perlstein, I., Burton, D.Y., Ryan, K., Defelice, S., Simmers, E., Campbell, B., Connolly, J.M., Hoffman, A., Levy, R.J. Hum. Gene Ther. (2005) [Pubmed]
  11. Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRP1 ion channel: implications for acquired and congenital long Q-T syndrome. Larsen, L.A., Andersen, P.S., Kanters, J., Svendsen, I.H., Jacobsen, J.R., Vuust, J., Wettrell, G., Tranebjaerg, L., Bathen, J., Christiansen, M. Clin. Chem. (2001) [Pubmed]
  12. KCNE2 modulates current amplitudes and activation kinetics of HCN4: influence of KCNE family members on HCN4 currents. Decher, N., Bundis, F., Vajna, R., Steinmeyer, K. Pflugers Arch. (2003) [Pubmed]
  13. Electrophysiological and molecular identification of hepatocellular volume-activated K+ channels. Lan, W.Z., Abbas, H., Lemay, A.M., Briggs, M.M., Hill, C.E. Biochim. Biophys. Acta (2005) [Pubmed]
  14. Colocalization of KCNQ1/KCNE channel subunits in the mouse gastrointestinal tract. Dedek, K., Waldegger, S. Pflugers Arch. (2001) [Pubmed]
  15. Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism. Abbott, G.W., Goldstein, S.A. FASEB J. (2002) [Pubmed]
  16. A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Sesti, F., Abbott, G.W., Wei, J., Murray, K.T., Saksena, S., Schwartz, P.J., Priori, S.G., Roden, D.M., George, A.L., Goldstein, S.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  17. Modulation of functional properties of KCNQ1 channel by association of KCNE1 and KCNE2. Toyoda, F., Ueyama, H., Ding, W.G., Matsuura, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  18. Torsades de pointes complicating atrioventricular block: Evidence for a genetic predisposition. Chevalier, P., Bellocq, C., Millat, G., Piqueras, E., Potet, F., Schott, J.J., Baró, I., Lemarec, H., Barhanin, J., Rousson, R., Rodriguez-Lafrasse, C. Heart rhythm : the official journal of the Heart Rhythm Society (2007) [Pubmed]
  19. Cyclic AMP regulates the HERG K(+) channel by dual pathways. Cui, J., Melman, Y., Palma, E., Fishman, G.I., McDonald, T.V. Curr. Biol. (2000) [Pubmed]
  20. KCNE2 is colocalized with KCNQ1 and KCNE1 in cardiac myocytes and may function as a negative modulator of I(Ks) current amplitude in the heart. Wu, D.M., Jiang, M., Zhang, M., Liu, X.S., Korolkova, Y.V., Tseng, G.N. Heart rhythm : the official journal of the Heart Rhythm Society (2006) [Pubmed]
  21. Effect of beta-adrenoceptor blockers on human ether-a-go-go-related gene (HERG) potassium channels. Dupuis, D.S., Klaerke, D.A., Olesen, S.P. Basic & clinical pharmacology & toxicology. (2005) [Pubmed]
  22. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. Paulussen, A.D., Gilissen, R.A., Armstrong, M., Doevendans, P.A., Verhasselt, P., Smeets, H.J., Schulze-Bahr, E., Haverkamp, W., Breithardt, G., Cohen, N., Aerssens, J. J. Mol. Med. (2004) [Pubmed]
  23. M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit. Tinel, N., Diochot, S., Lauritzen, I., Barhanin, J., Lazdunski, M., Borsotto, M. FEBS Lett. (2000) [Pubmed]
  24. Molecular and functional characterization of common polymorphisms in HERG (KCNH2) potassium channels. Anson, B.D., Ackerman, M.J., Tester, D.J., Will, M.L., Delisle, B.P., Anderson, C.L., January, C.T. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  25. Asymmetrical distribution of ion channels in canine and human left-ventricular wall: epicardium versus midmyocardium. Szabó, G., Szentandrássy, N., Bíró, T., Tóth, B.I., Czifra, G., Magyar, J., Bányász, T., Varró, A., Kovács, L., Nánási, P.P. Pflugers Arch. (2005) [Pubmed]
  26. Human immunoglobulin G antibody response to the major gonococcal iron-regulated protein. Fohn, M.J., Mietzner, T.A., Hubbard, T.W., Morse, S.A., Hook, E.W. Infect. Immun. (1987) [Pubmed]
  27. Cleavage of the protein III and major iron-regulated protein of Neisseria gonorrhoeae by lysosomal cathepsin G. Shafer, W.M., Morse, S.A. J. Gen. Microbiol. (1987) [Pubmed]
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