Disease relevance of CACNA1H

• The expression of CACNA1H in breast cancer was confirmed for the first time [1].
• A profile of alternative RNA splicing and transcript variation of CACNA1H, a human T-channel gene candidate for idiopathic generalized epilepsies [2].
• CACNA1H is a human gene encoding Ca(v)3.2 low-voltage-activated, T-type calcium channels associated with bursting behavior in neurons and has been linked to more than 30 mutations apparently predisposing to childhood absence epilepsy (CAE) and other idiopathic generalized epilepsies (IGEs) [2].
• PURPOSE OF REVIEW: Only two functionally validated susceptibility genes, CACNA1H and GABRD, have so far been identified in the common epilepsies using a candidate gene approach [3].

High impact information on CACNA1H

• The DNA regions identified contained MEL1, CACNA1H, and Nogo receptor genes [4].
• We mapped the gene, CACNA1H, to human chromosome 16p13.3 and mouse chromosome 17 [5].
• Taken together, these findings along with previous reports, strongly implicate CACNA1H as a susceptibility gene in complex idiopathic generalized epilepsy [6].
• Association between genetic variation of CACNA1H and childhood absence epilepsy [7].
• Here, we identify missense mutations in the calcium channel gene CACNA1H (T-type Ca(V)3.2) in 6 of 461 individuals with ASD [8].

Biological context of CACNA1H

• Heron and colleagues (Ann Neurol 2004;55:595-596) identified three missense mutations in the Cav3.2 T-type calcium channel gene (CACNA1H) in patients with idiopathic generalized epilepsy [6].
• Genetic variation of CACNA1H in idiopathic generalized epilepsy [9].
• Each gamma gene lies between an alpha1H Ca2+ channel gene (CACNA1H) and a betaII- or betaIII-tryptase gene and is approximately 30 kb from polymorphic minisatellite MS205 [10].
• In our previous studies, relatively high frequent variants in the T-type calcium channel gene, CACNA1H, were identified in the Chinese Han population, most of which are located in exons 6-12 [11].
• Sequencing of the T-type Ca2+ channel gene CACNA1H revealed 12 nonsynonymous single nucleotide polymorphisms (SNPs) that were found only in childhood absence epilepsy (CAE) patients [12].

Other interactions of CACNA1H

• We then used this fragment to screen human heart and rat brain lambda gt10 libraries, leading to the cloning of two full-length cDNAs derived from distinct genes (CACNA1G and CACNA1H) [13].
• Nucleotide sequencing and homology search analysis showed that these spots represented the voltage-dependent calcium channel alpha1H subunit gene (CACNA1H gene) and a locus immediately downstream of the growth factor receptor-binding protein 7 (GRB7) gene [1].
• Three T-channel genes were identified: CACNA1G, encoding Ca(v)3.1; CACNA1H, encoding Ca(v)3.2; and CACNA1I, encoding Ca(v)3 [14].

Analytical, diagnostic and therapeutic context of CACNA1H

• Expression of the CACNA1H gene was confirmed by RT-PCR [1].

References