Disease relevance of KCND3

• This information should facilitate the systematic screening of KCND2 and KCND3 exons for mutations in (inherited) arrhythmia syndromes, such as LQTS and Brugada [1].
• CONCLUSION: The data suggest that mutations in KCND2 and KCND3 are not a frequent cause of long QT syndrome [2].

High impact information on KCND3

• PharmGKB Submission Update: VII. PAT Submissions of Genetic Variation in KCND3 to the PharmGKB Network [3].
• OBJECTIVES: The function of Kv4.3 (KCND3) channels, which underlie the transient outward current I(to) in human heart, can be modulated by several accessory subunits such as KChIP2 and KCNE1-KCNE5 [4].
• The KCND3 gene contains an additional exon of 57 bp, which is not present in the other two KCND genes and gives rise to the C-terminal splice KCND3L variant with an insertion of 19 amino acids [5].
• We therefore resolved the intron-exon boundaries and flanking intronic sequences and found that KCND2 consisted of six exons and KCND3 of seven exons [1].
• Subsequently, we designed the oligonucleotide primers needed for amplifying the coding exons of both KCND2 and KCND3 and established conditions for polymerase chain reaction amplification of each exon from genomic DNA [1].

Biological context of KCND3

• RESULTS: Seven single nucleotide polymorphismsm (SNPs) were found, two exonic SNPs in KCND2 and three exonic and two intronic in KCND3 [2].
• METHODS: KCND2 and KCND3 were examined for mutations using single-strand conformation polymorphism (SSCP) analysis in 43 unrelated LQTS patients, where mutations in the coding regions of known LQTS genes had been excluded [2].

1. Genomic organisation and chromosomal localisation of two members of the KCND ion channel family, KCND2 and KCND3. Postma, A.V., Bezzina, C.R., de Vries, J.F., Wilde, A.A., Moorman, A.F., Mannens, M.M. Hum. Genet. (2000)
2. Mutations in the genes KCND2 and KCND3 encoding the ion channels Kv4.2 and Kv4.3, conducting the cardiac fast transient outward current (ITO,f), are not a frequent cause of long QT syndrome. Frank-Hansen, R., Larsen, L.A., Andersen, P., Jespersgaard, C., Christiansen, M. Clin. Chim. Acta (2005)
3. PharmGKB Submission Update: VII. PAT Submissions of Genetic Variation in KCND3 to the PharmGKB Network. Simard, C., Drolet, B., Roden, D. Pharmacol. Rev. (2006)
4. 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)
5. Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA). Isbrandt, D., Leicher, T., Waldschütz, R., Zhu, X., Luhmann, U., Michel, U., Sauter, K., Pongs, O. Genomics (2000)