"There is increasing evidence that de novo CACNA1D missense mutations inducing increased Cav1.3L-type Ca 2+ -channel-function confer a high risk for neurodevelopmental disorders (autism spectrum disorder with and without neurological and endocrine symptoms)."
"In the brain such rare CACNA1D variants inducing more subtle changes in Ca v 1.3 function may only be of disease relevance in a permissive genetic background."
"We presume that the reduced expression of CACNA1D in more aggressive prostate cancer and progressors may contribute to decreased Ca 2+ influx and results in the escape of apoptosis, thus suggesting that decreased CACNA1D expression could be a more aggressive phenotype in higher grade prostate cancer or progressors in AS."
"Cell based studies demonstrated that activating mutations in the CACNA1D gene can cause increased intracellular Ca 2+ influx, resulting in enhanced aldosterone production XREF_BIBR, XREF_BIBR and inhibitory effect of nifedipine on aldosterone production from H295R cells with mutant Ca v 1.3 was also observed 31."
"Other ion channel genes include CACNA1D, a voltage sensitive calcium channel regulator; KCNJ2, a regulator of potassium ion transport; CHRNG, a nicotinic cholinergic receptor; and MYO1D, a putative binder of calmodulin, which mediates Ca + sensitivity to KCNQ5 ion channels."
"These data strongly suggest that CACNA1D mutations enhancing Ca v 1.3 activity confer a strong risk for - or even cause - CNS disorders, such as ASD."
"Taken together, the human data corroborate the observations in INS-832/13 cells and rodent islets, showing that SOX5 overexpression induces expression changes opposite to that of T2D islets, increases CACNA1D expression and improves beta-cell function in T2D islets."
"The GWAS did not produce any SNP-cSCC associations that were genome-wide significant (p<5×10 −8 ) likely due to the relatively small number of cSCC cases, but SNPs associated with the biologically plausible genes CSMD1 and CACNA1D that could play a role in cSCC development were suggested."
"In line with the notion that these effects will lead to increased calcium entry, expression of mutant CACNA1D channels causes increased aldosterone production in the adrenocortical cancer cell line H295R."
"Mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 are thought to cause the excessive autonomous aldosterone secretion of aldosterone producing adenomas (APAs)."
"Importantly, individual silencing of CACNA1D or CACNA1S gene expression using multiple siRNA oligos (XREF_SUPPLEMENTARY) decreased both filopodia formation and cancer cell invasion (XREF_FIG), indicating that CACNA1D and CACNA1S are likely to synergistically support filopodia formation and cancer cell invasion in MDA-MB-231 cells."
"In particular, CACNA1D, which localizes to filopodia tips and contributes to cancer cell invasion in vitro (shown in this study), was found to be expressed in patient samples in all major breast cancer subtypes."
"XREF_BIBR - XREF_BIBR KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutation leads to increased intracellular Ca 2+ concentration, activation of Ca 2+ signaling, and an increase in CYP11B2 transcription."
"The GWAS did not produce any SNP-cSCC associations that were genome-wide significant (p<5×10 −8 ) likely due to the relatively small number of cSCC cases, but SNPs associated with the biologically plausible genes CSMD1 and CACNA1D that could play a role in cSCC development were suggested."
"In the present study, we show that one CACNA1D mutation (p.A749G in Cav1.3 alpha1), which has been reported as 1 of 62 high risk conferring mutations in a whole-exome sequencing (WES) study of patients with sporadic autism and intellectual disability, induces a strong increase in Cav1.3 channel function."
"The identification of an activating p.G403D mutation in 2 unrelated patients with congenital HH supports the role of CACNA1D as an aetiological gene for HH, and screening for mutations in this gene should be considered in an individual with HH in addition to heart defects."
"The expression of functionally different splice isoforms of Ca V 1.2 and Ca V 1.3 in different tissues enables Cacna1c and Cacna1d genes to support a wider range of calcium dependent cellular functions [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR]."
"To the best of knowledge, this is the first report describing a genetic association between CACNA1D and CD in two independent human samples, which corroborates the functional aspects of Ca v 1.3 in the mice models of cocaine behavior."
"We also found that biotin supplementation produced a substantial increase in the mRNA abundance of Cacna1d, which codes for a voltage dependent L-type calcium channel subunit importantly controlling Ca 2 + entry during insulin secretion [42]."
"Using a mammalian two-hybrid assay, they further showed that retinoschisin binds within a 500 amino acid N-terminal region of chicken CACNA1D gene, which is highly conserved in human CACNA1D and CACNA1F subunits."
"Importantly, as opposed to APA, CT-negative PA is primarily associated with mutations in CACNA1D . The availability of widely used anti-hypertensive CCBs supports investigations into the efficacy of these drugs to inhibit aldosterone production in IHA."
"In addition, whole-cell voltage-clamp recordings of Chinese hamster ovary cells stably expressing the alpha 1-subunit (rCACN4A or rCACN4B) with or without the calcium channel beta 2-subunit show that coexpression of rCACN4A with the beta 2-subunit or rCACN4B with the beta 2-subunit elicits L-type VDCC currents, whereas expression of the alpha 1-subunit alone does not, indicating that CACN4 can associate functionally with the beta 2-subunit and that the beta-subunit is essential for functional expression of CACN4."
"ATP2A1 , RYR2 , RYR1 , CACNA1C , CACNA1D , and CACNA1S mediate the release of calcium , thereby playing a key role in triggering cardiac muscle contraction and maintaining the calcium homeostasis [ 56,57 ] ."
"ATP1A1 (Na + / K + ATPase alpha-subunit) mutations result in cellular depolarization and subsequent calcium influx, whereas ATP2B3 (Ca 2+ ATPase) and CACNA1D (Ca v 1.3) mutations result in impaired intracellular calcium clearance and stimulation of the voltage gated calcium channels at lower depolarization levels, respectively."
"CACNA1D may simultaneously promote PCa cell growth and proliferation [XREF_BIBR], and thus play a generalized, supporting role in castration resistant cancer progression [XREF_BIBR]."
"CACNA1D may simultaneously promote PCa cell growth and proliferation [XREF_BIBR], and thus play a generalized, supporting role in castration resistant cancer progression [XREF_BIBR]."
"CACNA1D may simultaneously promote PCa cell growth and proliferation [XREF_BIBR], and thus play a generalized, supporting role in castration resistant cancer progression [XREF_BIBR]."
"To the best of knowledge, this is the first report describing a genetic association between CACNA1D and CD in two independent human samples, which corroborates the functional aspects of Ca v 1.3 in the mice models of cocaine behavior."
"The CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E and CACNA1G genes produce various isoform of alpha1 subunit including A, B, C, D, E and G, respectively."
"Although the subunit structure of the VOCC protein in pancretic {3-cells is not yet known, these findings suggest that the {3 subunit is necessary for CACN4 directed VOCC activity."
"CACNA1D can enhance the benefit of 5-FU-based ACT through regulating activity of the calcium channel.49 These transcriptional and genomic characteristics could shape 5-FU response and should be irrelevant of the primary tumor location of colon cancer patients."
"Using a mammalian two-hybrid assay, they further showed that retinoschisin binds within a 500 amino acid N-terminal region of chicken CACNA1D gene, which is highly conserved in human CACNA1D and CACNA1F subunits."
"Somatic and germline mutations in CACNA1D, which encodes a voltage gated calcium channel, have been reported to cause PA, as have somatic mutations in ATP1A1 and ATP2B3, a Na + / K + ATPase and a Ca 2+ -ATPase, respectively (XREF_TABLE)."
"We found that siRNA mediated depletion of CACNA1D, but not CACNA1A, completely suppressed NNK induced IGF-1R phosphorylation and IGF2 secretion (XREF_FIG)."
"We found that siRNA mediated depletion of CACNA1D, but not CACNA1A, completely suppressed NNK induced IGF-1R phosphorylation and IGF2 secretion (XREF_FIG)."
"Importantly, as opposed to APA, CT-negative PA is primarily associated with mutations in CACNA1D . The availability of widely used anti-hypertensive CCBs supports investigations into the efficacy of these drugs to inhibit aldosterone production in IHA."
"In addition, whole-cell voltage-clamp recordings of Chinese hamster ovary cells stably expressing the alpha 1-subunit (rCACN4A or rCACN4B) with or without the calcium channel beta 2-subunit show that coexpression of rCACN4A with the beta 2-subunit or rCACN4B with the beta 2-subunit elicits L-type VDCC currents, whereas expression of the alpha 1-subunit alone does not, indicating that CACN4 can associate functionally with the beta 2-subunit and that the beta-subunit is essential for functional expression of CACN4."
"Protein-protein interaction assays revealed interactions between clarin-1 and the synaptic CaV1.3 Ca2+ channel complex via the Cavβ2 auxiliary subunit and the PDZ domain-containing protein harmonin (defective in Usher syndrome type IC)."
"Based on the observation that these mutations cause functional changes compatible with a gain-of-function, and the known role of these channels for CNS function in rodents, we postulated that such gating modifying mutations in CACNA1D underlie ASD."
"At the same time, Stim1 interaction with CaV1.2 and CaV1.3 could help understanding Stim1 and Orai1 co-localization into puncta-like clusters upon ER depletion in mouse hippocampal and cortical neurons."
"The neuronal AKAP MAP2B, which also interacts with CaV1.2 and CaV1.3 channels, has complementary localization to AKAP15, suggesting different functional roles in calcium channel regulation."
"Most cases preoperatively classified as an APA are morphologically heterogeneous and the identification of somatic mutations in KCNJ5 , ATP1A1 , ATP2B3 and CACNA1D associated with the use of the recently developed monoclonal antibodies for aldosterone synthase and 11β-hydroxylase at least partially accounts for this histopathological heterogeneity."