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Table 3 Gene reported to associate with ID and availability of functional cell models, modulators and pathways

From: Calcium channelopathies and intellectual disability: a systematic review

Gene Name Subunit Current type Functional model (neuronal stem cells or other cell lines) for ID Other available functional models Modulators Disease pathway
CACNA1A Calcium voltage-gated channel subunit alpha1 A Cav2.1 P/Q-type Primary hippocampal rat cultures, HEK293T cells and TsA201 for synaptic plasticity [109] HEK293 cells for developmental epileptic encephalopathies [19]. Purkinje cells for spinocerebellar ataxia type 6 [279, 280]. Induced pluripotent stem cells (ZZUi0017-A) for spinocerebellar ataxia type 6 [281]. COS-7 cells for spinocerebellar ataxia type 2 [164]. Pheochromocytoma (pc12) cells for cerebellar disorders [282]. HEK293T cells for epilepsy [283]. SH-SY5Y for familial hemiplegic migraine type 1 and episodic ataxia [159]. Purkinje cells for absence epilepsy, dyskinesia, and ataxia phenotypes [284]. Cell-specific mouse mutant lines that suffer from impaired purkinje cell output (Pcd), purkinje cell potentiation (L7-Pp2b), molecular layer interneuron output (L7-Δγ2), and granule cell output (α6-Cacna1a) for cerebellar control of gait and interlimb coordination [285]. HEK293 cells for stroke-like episodes and ataxia [286]. HEK 293 cells for migraine with aura [287, 288]. Induced pluripotent stem cell line (ZZUi0018-A) for spinocerebellar ataxia type 6 [289]. HEK293 cells for episodic ataxia with epilepsy [290]. Human neuronal cell line (SK-N-SH) and HEK293 cells for spinocerebellar ataxia type 6 [160]. HEK cells for spinocerebellar ataxia type 6 [291]. Cultured hippocampal neurons and HEK cells for migraine [292]. HEK-293 and PC12 cells for spinocerebellar ataxia type 6 [191]. SH‑SY5Y cells for progressive myoclonic epilepsy [161] AAV9-mediated delivery of miR-3191-5p in mice rescued ataxia, motor deficits, and purkinje cell degeneration [165]
MiRNA-3191-5p prevented the hyperacute disease in hyperacute model of spinocerebellar ataxia type 6 mice [226]
SIS-RNAi could rescue spinocerebellar ataxia type 6 [160]
Barbiturate pentobarbital could block Cav2.1 current [166]
Acetazolamide had no effect on HEK cells carrying mutation for episodic ataxia type 2 [145]
Apoptotic pathway in progressive myoclonic epilepsy [161]
Apoptotic pathway in ataxia [191]
CACNA1C Calcium voltage-gated channel subunit alpha1 C Cav1.2 L-type None Human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) for long-QT syndrome phenotype [162]. Induced pluripotent stem cell (iPSC) knockout resource for autism spectrum disorder [163]. Huh7 cells for severe fever with thrombocytopenia syndrome [171]. Pancreatic insulinoma RIN-m5f β-cells for type 2 diabetes mellitus [250]. SA-201 and HEK293 cells for sudden unexplained death in the young [293]. OCI-ly7, OCI-ly8, and OCI-ly3 DLBCL cell lines for lymphoma [172]. Hippocampal HT22 cells for affective disorders [156]. Induced pluripotent stem cell (iPSC) line for long QT syndrome type 8 [294, 295]. H9C2 and rat myocytes in long QT syndrome type 2 [296]. Timothy syndrome cardiomyocytes for cardiac arrhythmias [174] Micro-RNA-137 targets the CACNA1C in mice and human neuroblastoma cells for Alzheimer's disease [167]
MiR-221 and -222 inhibit Cav1.2 current in HL-1 cells [168]
Nifedipine and benidipine hydrochloride inhibited severe fever with thrombocytopenia syndrome in Huh7 cells and in humanized mouse model [171]
MiR-153 inhibitors upregulate the expression of Cacna1c mRNA and protein [169]
Bay K8644 can prevent age related bone loss [173]
MiR-103 can suppress expression of Cav1.2 and thus inhibit osteoblast proliferation [170]
Estradiol can upregulates expression of Cav1.2 [148]
Roscovitine could rescue cardiac arrhythmias [174]
Stac2 and Stac3 can modulate CaV1.2 function [175]
Azelnidipine reduces the expression of Cav1.2 [176]
Wnt pathway for age‐related osteoporosis [173]
Apoptotic pathway in lymphoma [172]
Apoptotic pathway in melanoma [192]
Autophagic pathway in autism [197]
CACNA1D Calcium voltage-gated channel subunit alpha1 D Cav1.3 L-type TsA-201 cells for ID and autism [82, 84] TsA-201 cells in hearing [297]. Rat hippocampal and HEK293 cells for Alzheimer's disease [298] Isradipine could block Cav1.3 current in vitro [84] Apoptotic pathway [127]
CACNA1E Calcium voltage-gated channel subunit alpha1 E Cav2.3 R-type TsA201 cells for ID and epilepsy [85] None Sipatrigine, eugenol, and lamotrigine could block Cav2.3 current [177, 178] None
CACNA1F Calcium voltage-gated channel subunit alpha1 F Cav1.4 L-type None HEK293 and tsA-201 cells for congenital stationary night blindness type-2 [299] None None
CACNA1G Calcium voltage-gated channel subunit alpha1 G Cav3.1 T-type None COS-7 and rat islet cells for diabetes mellitus [300]. HEK293T cells for autosomal-dominant cerebellar ataxia [301]. Induced pluripotent stem cells (iPSCs) and HEK293T cells for spinocerebellar ataxia [302] Endostatin, zonisamide, clozapine, roscovitine, mibefradil, iron and zinc can block Cav3.1 channel [179,180,181,182,183,184,185]
Dearomatized isoprenylated acylphloroglucinol and monoterpenoid, hypatone A could rescue pathological gating properties for spinocerebellar ataxia 42 [186]
Autophagic pathway in melanoma cells [198]
Apoptotic pathway in [193,194,195]
Ras-ERK signaling pathway [200, 201]
CACNA1H Calcium voltage-gated channel subunit alpha1 H Cav3.2 T-type None TsA-201 cell for amyotrophic lateral sclerosis [303] KYS-05090S can block Cav3.2 current [187] Apoptotic pathway in myocardial cells [155]. Autophagy pathway [158]
CACNA1I Calcium Voltage-Gated Channel Subunit Alpha1 I Cav 3.3 T-type HEK293T and mouse chromaffin cells for ID and epilepsy [74] None Zinc modulates Cav3.3 channel gating [181] None
CACNA2D1 Calcium voltage-gated channel auxiliary subunit alpha2delta 1 Cav1.3 L-type None MKN74 cells (human gastric cancer cell line) [190] MicroRNA-107 can inhibit expression of Cav1.3 in cancer [188, 189]
Amlodipine can block Cav1.3 in cancer [190]
CXCR3/ERK1/2 signaling pathway [203]
Ras/Raf/MEK/ERK signaling pathway [202]
CACNA2D2 Calcium voltage-gated channel auxiliary subunit alpha2delta 2 Cav1.3 L-type None LNCaP, DU145 and PC3 cell lines for prostate cancer [151] None Apoptotic pathway [196]
Autophagic pathway [199]