Table 3.
S6 channelopathies of voltage-dependent K+ channels
ChannelGeneUnitary cond. Tissue expressionS6 limitsMutationDiseaseReference
  pS       
Kv1.1 KCNA1 8.7–20 Central nervous system, kidney, and heart 387–415 V404I, V408A Episodic ataxia EA1 Browne et al., 1994; Scheffer et al., 1998  
Kv1.2 KCNA2 14–18 Neocortex, hippocampus, main olfactory bulb, and cerebellum 389–417 P405L Early infantile epileptic encephalopathy, 32 EIEE32 Syrbe et al., 2015  
Kv2.1 KCNB1 14 Hippocampal neurons and cortical neurons 392–420 G401R Early infantile epileptic encephalopathy, 26 EIEE26 Saitsu et al., 2015  
Kv3.3 KCNC3 32–38 Cerebellum, basal ganglia, and spinal cord 518–539 V535M Spinocerebellar ataxia 13 SCA13 Duarri et al., 2015  
Kv4.3 KCND3 Substantia nigra pars compact, retrosplenial cortex, superior colliculus, the raphe nuclei and amygdala, olfactory bulb, and dentate gyrus 382–402 S390N; V392I Spinocerebellar ataxia 19; Brugada syndrome SCA19; BRGDA9 Duarri et al., 2012; Giudicessi et al., 2012  
Kv7.1 KCNQ1 0.7–4 Heart, uterus, stomach, small and large intestine, kidney and pancreas; smooth muscle 328–348 F339Y, A341E/G/V, L342F, P343L/R/S, A344E/V, G345E/R Long QT síndrome type 1 LQT1 Jongbloed et al., 1999; Tester et al., 2005; Kapplinger et al., 2009  
Kv7.2 KCNQ2 6.5 Hippocampal and cortical neurons 292–312 A306T Benign familial neonatal seizures BFNS1 Singh et al., 2003  
Kv7.4 KCNQ4 2.1 Brain, cochlea, heart, and skeletal muscle; neuron derived from embryonic stem cells 297–317 G321S Deafness autosomal dominant 2A DFNA2A Coucke et al., 1999  
Kv10.1 EAG KCNH1 8.5 Brain, kidney, lung, and pancreas; in brain: in cortex, hippocampus, caudate, putamen, amígdala, and substantia nigra 478–498 L489F, I494V Temple-Baraitser syndrome and epilepsy TMBTS Simons et al., 2015  
Kv11.1 ERG KCNH2 10–13 Brian: reticular thalamic nucleus, cerebral cortex, cerebellum, and hippocampus; heart 639–659 F640L/V, S641F, V644F/L, M645I/L, G648S, F656C, G657R Long QT syndrome 2 LGT2 Napolitano et al., 2005; Tester et al., 2005; Kapplinger et al., 2009  
KCa3.1 KCNN4 30–80 Nonexcitable tissues 265–285 V282E/M Dehydrated hereditary stomatocytosis DHS2 Glogowska et al., 2015  
TASK 3 KCNK9 16–32 Cerebellum and external plexiform layer of the olfactory bulb; hippocampus 219–239 G236R Birk-Barel mental retardation dysmorphism BIBAS Barel et al., 2008  
ChannelGeneUnitary cond. Tissue expressionS6 limitsMutationDiseaseReference
  pS       
Kv1.1 KCNA1 8.7–20 Central nervous system, kidney, and heart 387–415 V404I, V408A Episodic ataxia EA1 Browne et al., 1994; Scheffer et al., 1998  
Kv1.2 KCNA2 14–18 Neocortex, hippocampus, main olfactory bulb, and cerebellum 389–417 P405L Early infantile epileptic encephalopathy, 32 EIEE32 Syrbe et al., 2015  
Kv2.1 KCNB1 14 Hippocampal neurons and cortical neurons 392–420 G401R Early infantile epileptic encephalopathy, 26 EIEE26 Saitsu et al., 2015  
Kv3.3 KCNC3 32–38 Cerebellum, basal ganglia, and spinal cord 518–539 V535M Spinocerebellar ataxia 13 SCA13 Duarri et al., 2015  
Kv4.3 KCND3 Substantia nigra pars compact, retrosplenial cortex, superior colliculus, the raphe nuclei and amygdala, olfactory bulb, and dentate gyrus 382–402 S390N; V392I Spinocerebellar ataxia 19; Brugada syndrome SCA19; BRGDA9 Duarri et al., 2012; Giudicessi et al., 2012  
Kv7.1 KCNQ1 0.7–4 Heart, uterus, stomach, small and large intestine, kidney and pancreas; smooth muscle 328–348 F339Y, A341E/G/V, L342F, P343L/R/S, A344E/V, G345E/R Long QT síndrome type 1 LQT1 Jongbloed et al., 1999; Tester et al., 2005; Kapplinger et al., 2009  
Kv7.2 KCNQ2 6.5 Hippocampal and cortical neurons 292–312 A306T Benign familial neonatal seizures BFNS1 Singh et al., 2003  
Kv7.4 KCNQ4 2.1 Brain, cochlea, heart, and skeletal muscle; neuron derived from embryonic stem cells 297–317 G321S Deafness autosomal dominant 2A DFNA2A Coucke et al., 1999  
Kv10.1 EAG KCNH1 8.5 Brain, kidney, lung, and pancreas; in brain: in cortex, hippocampus, caudate, putamen, amígdala, and substantia nigra 478–498 L489F, I494V Temple-Baraitser syndrome and epilepsy TMBTS Simons et al., 2015  
Kv11.1 ERG KCNH2 10–13 Brian: reticular thalamic nucleus, cerebral cortex, cerebellum, and hippocampus; heart 639–659 F640L/V, S641F, V644F/L, M645I/L, G648S, F656C, G657R Long QT syndrome 2 LGT2 Napolitano et al., 2005; Tester et al., 2005; Kapplinger et al., 2009  
KCa3.1 KCNN4 30–80 Nonexcitable tissues 265–285 V282E/M Dehydrated hereditary stomatocytosis DHS2 Glogowska et al., 2015  
TASK 3 KCNK9 16–32 Cerebellum and external plexiform layer of the olfactory bulb; hippocampus 219–239 G236R Birk-Barel mental retardation dysmorphism BIBAS Barel et al., 2008  

Non-exhaustive listing of mutations potentially affecting unitary conductance in voltage-gated K+ channel. Mutational data as well as topological composition of S6 transmembrane segments were obtained from UniProt (http://www.uniprot.org/uniprot/).

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