Alternative titles; symbols
Other entities represented in this entry:
HGNC Approved Gene Symbol: KCND3
SNOMEDCT: 719251009;
Cytogenetic location: 1p13.2 Genomic coordinates (GRCh38) : 1:111,770,662-111,989,668 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1p13.2 | Brugada syndrome 9 | 616399 | Autosomal dominant | 3 |
| Spinocerebellar ataxia 19 | 607346 | Autosomal dominant | 3 |
The KCND3 gene encodes Kv4.3, an alpha subunit of the Shal family of A-type voltage-gated potassium channels, which are important in membrane repolarization in excitable cells (summary by Lee et al., 2012).
By screening a cardiac cDNA library and RT-PCR of human ventricular RNA, Kong et al. (1998) isolated a cDNA encoding KCND3. The deduced 637-amino acid protein shares 99% sequence homology with the rat homolog. KCND3 contains 6 transmembrane segments and intracellular N- and C-termini. RT-PCR and sequence analysis demonstrated the existence of a splice variant, KCND3L, with an insert encoding an additional 19 amino acids and containing a phosphorylation site. The shorter isoform was designated KCND3S. Zhu et al. (1999) found that the KCND3L, KCND1 (300281), and KCND2 (605410) proteins share 60% sequence identity and 71% homology, with the least conservation in the C terminus. By Northern blot analysis, Kong et al. (1998) detected expression of an 8.5-kb transcript that is most abundant in brain and heart and is not detectable in kidney, liver, lung, pancreas, spleen, or skeletal muscle. By the same method, Isbrandt et al. (2000) found that expression within the brain is greatest in the cerebral cortex. By RT-PCR analysis, they found that the long transcript predominates in thalamus, caudate nucleus, white matter, and epiphysis, whereas the short transcript is more abundant in frontal cortex, occipital lobe, and cerebellar cortex. Dilks et al. (1999), who cloned KCND3 from human heart and brain, found by RT-PCR that only the long form of KCND3 is expressed in heart. Isbrandt et al. (2000) determined that the long form of the KCND3 gene contains 7 exons and spans at least 25 kb. The shorter isoform is encoded by 6 exons. Kong et al. (1998) and Dilks et al. (1999) found no differences in the splice variants in terms of their voltage dependence or inactivation kinetics in the basal state.
In human cerebellar tissue, Duarri et al. (2012) found weak, punctuated immunostaining for the KCND3 gene in Purkinje cell bodies.
The transient outward potassium current, I(to), is especially important during the early phase of repolarization in many species, including human, as it sets the plateau voltage of both the atrial and the ventricular action potential. KCND2 and/or KCND3 code for the primary alpha subunits responsible for I(to) (Tseng, 1999). In the human ventricle, KCND3 is the gene that encodes the K+ channel that underlies I(to) (Dixon et al., 1996).
By FISH, Kong et al. (1998) mapped the KCND3 gene to chromosome 1p13.3. By radiation hybrid mapping, Postma et al. (2000) assigned the gene to 1p13.2.
Spinocerebellar Ataxia 19
In affected members of a Han Chinese family with spinocerebellar ataxia-19 (SCA19; 607346), originally reported by Chung et al. (2003) as having SCA22, Lee et al. (2012) identified a heterozygous 3-bp deletion in the KCND3 gene (605411.0001). The same heterozygous deletion was found in affected members of a French family with autosomal dominant SCA. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. In HEK293 cells, the mutant protein showed no discernible cell surface expression and appeared to be abnormally retained within the endoplasmic reticulum. Voltage-clamp recordings showed decreased outward potassium currents compared to wildtype cells in response to voltage. Three additional heterozygous missense variants were found in the KCND3 gene (G345V, V338E, or T377M) in an Ashkenazi Jewish family and in 3 of 55 Japanese families with late-onset SCA, but segregation of the variants with the phenotype was unclear and no functional studies were performed on these variants. No KCND3 mutations were found in probands from 105 Chinese families with hereditary ataxia.
In affected members of a large Dutch family with SCA19, originally reported by Schelhaas et al. (2001), Duarri et al. (2012) identified a heterozygous mutation in the KCND3 gene (T352P; 605411.0002). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Transfection of the mutation into HeLa cells showed that the mutant protein had almost no cell surface expression, but rather accumulated in the endoplasmic reticulum, consistent with a trafficking defect. The mutant protein was more rapidly degraded compared to the wildtype protein, suggesting that it was misfolded. The trafficking and degradation defects could be rescued by coexpression with the active isoform of KCHIP2 (604661). Patch-clamp recordings showed that the mutant channel had almost no detectable current activity (1% compared to wildtype). Duarri et al. (2012) suggested a dominant-negative effect and hypothesized that abnormal channel function may cause cellular toxicity due to abnormal intracellular calcium homeostasis, defects in long-term potentiation or depression, or chronic activation of the ER stress response. Two additional missense variants were identified in 2 probands, but segregation of the variants within the families was unclear.
In a 10-year-old boy with SCA19, Smets et al. (2015) identified a de novo heterozygous 9-bp duplication in the KCND3 gene (605411.0008). The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Studies to assess the effects of the duplication showed that the mutant protein was properly localized in the cell, but that it had significantly decreased protein stability. The mutation caused a strong shift in the voltage-dependence of activation and inactivation.
In 16 patients from 2 unrelated French families with SCA19, Huin et al. (2017) identified the 3-bp deletion in the KCND3 gene (605411.0001) that had previously been reported by Lee et al. (2012). In addition to typical features associated with SCA, 8 patients had mild parkinsonism and 5 had epilepsy.
In a 30-year-old Japanese man with SCA19, Kurihara et al. (2018) identified a de novo heterozygous missense mutation in the KCND3 gene (G384S; 605411.0009). The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or an in-house dataset of 800 healthy persons.
By screening of a Han Chinese cohort of patients with inherited cerebellar ataxias in Taiwan, Hsiao et al. (2019) identified 2 heterozygous variants in the KCND3 gene: a de novo c.950G-A transition in exon 2, resulting in a cys317-to-tyr (C317Y) substitution in 1 patient (pedigree A), and a c.1123C-T transition in exon 3, resulting in a pro375-to-ser (P375S) substitution in a mother and son (pedigree B). The authors then performed functional studies on these 2 mutations as well as on 2 previously reported missense mutations in the KCND3 gene. Electrophysiologic analyses showed that these mutations were associated with loss-of-function phenotypes. Additional studies showed that the mutations were associated with protein degradation and abnormal membrane trafficking. Coexpression of the wildtype with disease-related mutations provided evidence of dominant-negative effects of the mutations on protein biosynthesis and voltage-dependent gating of the Kv4.3 wildtype channel.
Brugada Syndrome 9
In a cohort of 86 patients with Brugada syndrome (see BRGDA9, 616399) who were negative for mutation in 8 known Brugada-associated genes, Giudicessi et al. (2011) analyzed the candidate gene KCND3 and identified heterozygous missense mutations in 2 unrelated patients, L450F (605411.0005) and G600R (605411.0006). Functional analysis demonstrated that both variants were gain-of-function mutations.
Using DNA samples from 123 cases of sudden unexplained death that had already been screened for mutation in 7 major and 12 minor channelopathy-associated genes, Giudicessi et al. (2012) analyzed the KCND3 gene and identified heterozygosity for missense mutations in 2 cases, the G600R mutation in 1 case and a V392I mutation (605411.0007) in the other. The V392I mutation was shown to be a gain-of-function change in functional studies, which also confirmed the gain-of-function nature of the G600R mutation. No KCND3 pathogenic variants were detected in 192 cases of sudden infant death syndrome (SIDS; see 272120).
In affected members of a Han Chinese family with spinocerebellar ataxia-19 (SCA19; 607346), originally reported by Chung et al. (2003), Lee et al. (2012) identified a heterozygous 3-bp deletion (c.679_681delTTC) in the KCND3 gene, resulting in the deletion of residue Phe227, a highly conserved residue in the S2 transmembrane domain. The same heterozygous deletion was found in affected members of a French family with autosomal dominant SCA. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. The mutation was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, in 500 Taiwanese-Chinese controls, or in 152 French controls. In HEK293 cells, the mutant protein showed no discernible cell surface expression and appeared to be abnormally retained within the endoplasmic reticulum. Voltage-clamp recordings showed decreased outward potassium currents compared to wildtype cells in response to voltage.
In 16 patients from 2 unrelated French families with SCA19, Huin et al. (2017) identified heterozygosity for the c.679_681delTTC mutation in the KCND3 gene. In addition to typical features associated with the disorder, 8 patients had mild parkinsonism and 5 had epilepsy.
In affected members of a large Dutch family with spinocerebellar ataxia-19 (SCA19; 607346), originally reported by Schelhaas et al. (2001), Duarri et al. (2012) identified a heterozygous c.1054A-C transversion in the KCND3 gene, resulting in a thr352-to-pro (T352P) substitution at a highly conserved residue in the third extracellular loop. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 800 Dutch control chromosomes. Cerebellar tissue from 1 affected individual showed intense KCND3 staining within large puncta in the soma of Purkinje cells. Transfection of the mutation into HeLa cells showed that the mutant protein had almost no cell surface expression, but rather accumulated in the endoplasmic reticulum, consistent with a trafficking defect. The mutant protein was more rapidly degraded compared to the wildtype protein, suggesting that it was misfolded. The trafficking and degradation defects could be rescued by coexpression with the active isoform of KCHIP2 (604661). Patch-clamp recordings showed that the mutant channel had almost no detectable current activity (1% compared to wildtype).
This variant is classified as a variant of unknown significance because its contribution to spinocerebellar ataxia-19 (607346) has not been confirmed.
In a Dutch father and daughter with late-onset spinocerebellar ataxia, Duarri et al. (2012) identified a heterozygous c.1119G-A transition in the KCND3 gene, resulting in a met373-to-ile (M373I) substitution at a highly conserved residue. The mutation was initially found by direct sequencing of the KCND3 gene in 230 Dutch probands with ataxia in whom mutations in several known SCA genes were not identified. It was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 800 Dutch control chromosomes. The proband had ambiguous neurologic signs on testing at age 44 years, and later had no neurologic signs at age 52 years, consistent with being an asymptomatic carrier. He had a relevant family history, with both his father and a sister showing signs of the disorder. His father was more severely affected, with onset of progressive ataxic gait at age 55 years, dysarthria, and cerebellar atrophy on brain MRI. His sister had very mild gait impairment at age 64 years. Transfection of the M373I mutation into HeLa cells showed that the mutant protein had almost no cell surface expression, but rather accumulated in the endoplasmic reticulum, consistent with a trafficking defect. The mutant protein was more rapidly degraded compared to the wildtype protein, suggesting that it was misfolded. The trafficking and degradation defects could be rescued by coexpression with the active isoform of KCHIP2 (604661). Patch-clamp recordings showed that the mutant channel had decreased current activity (25% of controls).
This variant is classified as a variant of unknown significance because its contribution to spinocerebellar ataxia-19 (607346) has not been confirmed.
In a Dutch man with slowly progressive spinocerebellar ataxia with onset at age 30 years, Duarri et al. (2012) identified a heterozygous c.1169G-A transition in the KCND3 gene, resulting in a ser390-to-asn (S390N) substitution at a highly conserved residue. The mutation was found by direct sequencing of the KCND3 gene in 230 Dutch probands with ataxia in whom mutations in several known SCA genes were not identified. It was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 800 Dutch control chromosomes. The patient had spastic ataxia, dysarthria, saccadic eye movements, nystagmus, cognitive impairment, hearing deficits, and cerebellar atrophy on brain imaging. The patient's mother and brother were diagnosed with a similar disorder, but genetic material was not available from them to confirm cosegregation of the S390N variant with the disorder. Transfection of the S390N mutation into HeLa cells showed that the mutant protein had almost no cell surface expression, but rather accumulated in the endoplasmic reticulum, consistent with a trafficking defect. The mutant protein was more rapidly degraded compared to the wildtype protein, suggesting that it was misfolded. The trafficking and degradation defects were unable to be rescued by coexpression with the active isoform of KCHIP2 (604661). Patch-clamp recordings showed that the mutant channel had decreased current activity (13% of controls).
In a 45-year-old man with Brugada syndrome (BRGDA9; 616399), Giudicessi et al. (2011) identified heterozygosity for a c.348C-T transition in the KCND3 gene, resulting in a leu450-to-phe (L450F) substitution at a highly conserved residue in the Kv4.3 carboxyl C terminus. The mutation was not found in 1,560 reference alleles. Functional analysis in HEK293 cells showed significantly increased transient outward current density at 0 mV and at 40 mV with the L450F mutant, by 154.3% and 146.2% over wildtype. In addition, the L450F mutant significantly increased the total charge of the transient outward current at 40 mV, by 117% over wildtype, and significantly shifted inactivation kinetics.
You et al. (2015) generated rat Kv4.3 with either a G581R or L450F mutation, corresponding to the human G600R (605411.0006) and L450F mutations associated with Brugada syndrome, respectively. Expression of mutant Kv4.3 with Kchip2 in HEK293 cells showed that the mutants caused a gain of function of the transient outward K+ currents, as the mutants increased Kv4.3 protein expression and influenced the kinetics of the transient outward K+ currents by slowing down channel inactivation. Furthermore, the Kv4.3 mutants enhanced membrane localization of the Kv4.3 protein, but they did not affect the mRNA level of Kv4.3.
In a 22-year-old man with Brugada syndrome (BRGDA9; 616399), Giudicessi et al. (2011) identified heterozygosity for a c.1798G-C transversion (later reported by Giudicessi et al. (2012) as a c.1798G-A transition) in the KCND3 gene, resulting in a gly600-to-arg (G600R) substitution at a highly conserved residue in the Kv4.3 C terminus. The mutation was not found in 1,560 reference alleles. Functional analysis in HEK293 cells showed significantly increased transient outward current density at 0 mV and at 40 mV with the G600R mutant, by 48.1% and 50.4% over wildtype. In addition, the G600R mutant exhibited significantly slower inactivation across the 0 to 40 mV range and a significantly increased total charge of the transient outward current at 40 mV compared to wildtype.
Using DNA from a 23-year-old asymptomatic male athlete who died from cardiopulmonary arrest while swimming laps, Giudicessi et al. (2012) identified heterozygosity for the G600R substitution in the KCND3 gene. The variant (rs149344567) was not found in 1,560 reference alleles or in the 1000 Genomes Project database; it was found in a single individual in the dbSNP (build 134) database. Premortem electrocardiograms (ECGs) from the proband were unavailable. There was no family history of sudden unexplained death, and screening ECGs in his parents and sister were reportedly normal. Family members declined to provide DNA for genetic testing. Functional analysis in HEK293 cells confirmed the marked gain-of-function electrophysiologic phenotype with the G600R variant.
You et al. (2015) generated rat Kv4.3 with either a G581R or L450F mutation, corresponding to the human G600R and L450F (605411.0005) mutations associated with Brugada syndrome, respectively. Expression of mutant Kv4.3 with Kchip2 in HEK293 cells showed that the mutants caused a gain of function of the transient outward K+ currents, as the mutants increased Kv4.3 protein expression and influenced the kinetics of the transient outward K+ currents by slowing down channel inactivation. Furthermore, the Kv4.3 mutants enhanced membrane localization of the Kv4.3 protein, but they did not affect the mRNA level of Kv4.3.
In a DNA sample from a 20-year-old man with a history of syncopal episodes who was found unresponsive in bed and could not be resuscitated (BRGDA9; 616399), Giudicessi et al. (2012) identified heterozygosity for a c.1174G-A transition in the KCND3 gene, resulting in a val392-to-ile (V392I) substitution at a conserved residue. The variant was not found in 1,560 reference alleles or in the 1000 Genomes Project or dbSNP (build 134) databases. Premortem electrocardiograms (ECGs) from the proband were unavailable, and family members declined to participate in the study. Functional analysis in HEK293 cells demonstrated that the V392I-mutant Kv4.3 channel dramatically increases both peak transient outward current density (100.4%) and total charge (298.7%), while slowing decay time (138%), indicating a gain of function. However, the V392I mutant also slows the recovery from inactivation (360.9%), suggesting a mixed electrophysiologic phenotype. Giudicessi et al. (2012) stated that this patient's death during sleep was consistent with a Brugada syndrome-like gain of function as the primary underlying etiology, with a Brugada syndrome-triggered fatal arrhythmia as the chief arrhythmia phenotype.
In a 10-year-old boy with spinocerebellar ataxia-19 (SCA19; 607346), Smets et al. (2015) identified a de novo heterozygous 9-bp duplication (c.877_885dupCGCGTCTTC, NM_004980.4) in the KCND3 gene, resulting in a 3-amino acid duplication (Arg293_Phe295dup) of the RVF (Arg-Val-Phe) domain in the S4 segment of Kv4.3. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype in the family. Studies to assess the effects of the duplication showed that the mutant protein was properly localized in the cell, but that it had significantly decreased stability. The mutation caused a strong shift in the voltage-dependence of activation and inactivation.
In a 30-year-old Japanese man with spinocerebellar ataxia-19 (SCA19; 607346), Kurihara et al. (2018) identified a de novo heterozygous c.1150G-A transition in the KCND3 gene, resulting in a gly384-to-ser (G384S) substitution. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or an in-house dataset of 800 healthy persons.
Chung, M., Lu, Y.-C., Cheng, N.-C., Soong, B.-W. A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. Brain 126: 1293-1299, 2003. [PubMed: 12764052] [Full Text: https://doi.org/10.1093/brain/awg130]
Dilks, D., Ling, H.-P., Cockett, M., Sokol, P., Numann, R. Cloning and expression of the human Kv4.3 potassium channel. J. Neurophysiol. 81: 1974-1977, 1999. [PubMed: 10200233] [Full Text: https://doi.org/10.1152/jn.1999.81.4.1974]
Dixon, J. E., Shi, W., Wang, H.-S., McDonald, C., Yu, H., Wymore, R. S., Cohen, I. S., McKinnon, D. Role of the Kv4.3 K+ channel in ventricular muscle: a molecular correlate for the transient outward current. Circ. Res. 79: 659-668, 1996. Note: Erratum: Circ. Res. 80: 147 only, 1997. [PubMed: 8831489] [Full Text: https://doi.org/10.1161/01.res.79.4.659]
Duarri, A., Jezierska, J., Fokkens, M., Meijer, M., Schelhaas, H. J., den Dunnen, W. F. A., van Dijk, F., Verschuuren-Bemelmans, C., Hageman, G., van de Vlies, P., Kusters, B., van de Warrenburg, B. P., Kremer, B., Wijmenga, C., Sinke, R. J., Swertz, M. A., Kampinga, H. H., Boddeke, E., Verbeek, D. S. Mutations in potassium channel KCND3 cause spinocerebellar ataxia type 19. Ann. Neurol. 72: 870-880, 2012. [PubMed: 23280838] [Full Text: https://doi.org/10.1002/ana.23700]
Giudicessi, J. R., Ye, D., Kritzberger, C. J., Nesterenko, V. V., Tester, D. J., Antzelevitch, C., Ackerman, M. J. Novel mutations in the KCND3-encoded Kv4.3 K+ channel associated with autopsy-negative sudden unexplained death. Hum. Mutat. 33: 989-997, 2012. [PubMed: 22457051] [Full Text: https://doi.org/10.1002/humu.22058]
Giudicessi, J. R., Ye, D., Tester, D. J., Crotti, L., Mugione, A., Nesterenko, V. V., Albertson, R. M., Antzelevitch, C., Schwartz, P. J., Ackerman, M. J. Transient outward current (I-to) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome. Heart Rhythm 8: 1024-1032, 2011. [PubMed: 21349352] [Full Text: https://doi.org/10.1016/j.hrthm.2011.02.021]
Hsiao, C. T., Fu, S. J., Liu, Y. T., Lu, Y. H., Zhong, C. Y., Tang, C. Y., Soong, B. W., Jeng, C. J. Novel SCA19/22-associated KCND3 mutations disrupt human KV 4.3 protein biosynthesis and channel gating. Hum. Mutat. 40: 2088-2107, 2019. [PubMed: 31293010] [Full Text: https://doi.org/10.1002/humu.23865]
Huin, V., Strubi-Vuillaume, I., Dujardin, K., Brion, M., Delliaux, M., Dellacherie, D., Cuvellier, J. C., Cuisset, J. M., Riquet, A., Moreau, C., Defebvre, L., Sablonniere, B., Devos, D. Expanding the phenotype of SCA19/22: parkinsonism, cognitive impairment and epilepsy. Parkinsonism Relat. Disord. 45: 85-89, 2017. [PubMed: 28947073] [Full Text: https://doi.org/10.1016/j.parkreldis.2017.09.014]
Isbrandt, D., Leicher, T., Waldschutz, R., Zhu, X., Luhmann, U., Michel, U., Sauter, K., Pongs, O. Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(to) and I(sa). Genomics 64: 144-154, 2000. [PubMed: 10729221] [Full Text: https://doi.org/10.1006/geno.2000.6117]
Kong, W., Po, S., Yamagishi, T., Ashen, M. D., Stetten, G., Tomaselli, G. F. Isolation and characterization of the human gene encoding I(to): further diversity by alternative mRNA splicing. Am. J. Physiol. 275: H1963-H1970, 1998. [PubMed: 9843794] [Full Text: https://doi.org/10.1152/ajpheart.1998.275.6.H1963]
Kurihara, M., Ishiura, H., Sasaki, T., Otsuka, J., Hayashi, T., Terao, Y., Matsukawa, T., Mitsui, J., Kaneko, J., Nishiyama, K., Doi, K., Yoshimura, J., Morishita, S., Shimizu, J., Tsuji, S. Novel de novo KCND3 mutation in a Japanese patient with intellectual disability, cerebellar ataxia, myoclonus, and dystonia. Cerebellum 17: 237-242, 2018. [PubMed: 28895081] [Full Text: https://doi.org/10.1007/s12311-017-0883-4]
Lee, Y.-C., Durr, A., Majczenko, K., Huang, Y.-H., Liu, Y.-C., Lien, C.-C., Tsai, P.-C., Ichikawa, Y., Goto, J., Monin, M.-L., Li, J. Z., Chung, M.-Y., and 10 others. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann. Neurol. 72: 859-869, 2012. [PubMed: 23280837] [Full Text: https://doi.org/10.1002/ana.23701]
Postma, A. V., Bezzina, C. R., de Vries, J. F., Wilde, A. A. M., Moorman, A. F. M., Mannens, M. M. A. M. Genomic organisation and chromosomal localisation of two members of the KCND ion channel family, KCND2 and KCND3. Hum. Genet. 106: 614-619, 2000. [PubMed: 10942109] [Full Text: https://doi.org/10.1007/s004390000308]
Schelhaas, H. J., Ippel, P. F., Hageman, G., Sinke, R. J., van der Laan, E. N., Beemer, F. A. Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia. J. Neurol. 248: 113-120, 2001. [PubMed: 11284128] [Full Text: https://doi.org/10.1007/s004150170245]
Smets, K., Duarri, A., Deconinck, T., Ceulemans, B., van de Warrenburg, B. P., Zuchner, S., Gonzalez, M. A., Schule, R., Synofzik, M., Van der Aa, N., De Jonghe, P., Verbeek, D. S., Baets, J. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy. BMC Med. Genet. 16: 51, 2015. [PubMed: 26189493] [Full Text: https://doi.org/10.1186/s12881-015-0200-3]
Tseng, G.-N. Molecular structure of cardiac I(to) channels: Kv4.2, Kv4.3, and other possibilities? Cardiovasc. Res. 41: 16-18, 1999. [PubMed: 10325948] [Full Text: https://doi.org/10.1016/s0008-6363(98)00282-x]
You, T., Mao, W., Cai, B., Li, F., Xu, H. Two novel Brugada syndrome-associated mutations increase Kv4.3 membrane expression and function. Int. J. Molec. Med. 36: 309-315, 2015. [PubMed: 26016905] [Full Text: https://doi.org/10.3892/ijmm.2015.2223]
Zhu, X. R., Wulf, A., Schwarz, M., Isbrandt, D., Pongs, O. Characterization of human Kv4.2 mediating a rapidly-inactivating transient voltage-sensitive K+ current. Receptors Channels 6: 387-400, 1999. [PubMed: 10551270]