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 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] |
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] |