Disease relevance of KCNAB2

• In contrast, of those not deleted for KCNAB2, only 27% have chronic seizures, and none had infantile spasms [1].

High impact information on KCNAB2

• We report here the cloning of a voltage-gated K+ channel beta subunit, hKv beta 3, from adult human left ventricle that shows 84% and 74% amino acid sequence identity with the previously cloned rat Kv beta 1 and Kv beta 2 subunits, respectively [2].
• Kv beta1.1 and Kv beta 2 point mutants lacking a key catalytic tyrosine residue found in the active site of all aldo-keto reductases have wild-type trafficking characteristics [3].
• The crystallographic structure of the Kv beta2 subunit revealed surprising structural homology with aldo-keto reductases, including a triosephosphate isomerase barrel structure, conservation of key catalytic residues, and a bound NADP(+) cofactor (Gulbis, J. M., Mann, S., and MacKinnon, R. (1999) Cell 90, 943-952) [3].
• The SHREW1 and KCNAB2 genes both had tissue-restricted expression patterns, including expression in the nervous system [4].
• The human tandem P domain K+ channel hTREK-1 (KCNK2) is distributed widely through the CNS [5].

Biological context of KCNAB2

• The human Kv beta 1.2 gene (KCNA2B) resides on chromosome 1, as indicated by somatic cell hybrid mapping, and has been localized by FISH to 1p36.3 [6].
• Because ion channels are important determinants of seizure susceptibility and the voltage-gated K(+) channel beta-subunit gene, KCNAB2, has been localized to 1p36, we propose that deletion of this gene may be associated with the epilepsy phenotype [1].
• Hemizygosity of this gene in a majority of monosomy 1p36 syndrome patients with epilepsy suggests that haploinsufficiency for KCNAB2 is a significant risk factor for epilepsy [1].

Other interactions of KCNAB2

• Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome [1].

Analytical, diagnostic and therapeutic context of KCNAB2

• METHODS: Twenty-four patients were evaluated by fluorescence in situ hybridization with a probe containing KCNAB2 [1].
• RESULTS: Nine patients are deleted for the KCNAB2 locus, and eight (89%) of these have epilepsy or epileptiform activity on EEG [1].

References