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Cav1.3

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Target id: 530

Nomenclature: Cav1.3

Family: Voltage-gated calcium channels (CaV)

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 4 2161 3p21.1 CACNA1D calcium voltage-gated channel subunit alpha1 D 35,61
Mouse 24 4 2179 14 B Cacna1d calcium channel, voltage-dependent, L type, alpha 1D subunit 78
Rat 24 4 2203 16p16 Cacna1d calcium voltage-gated channel subunit alpha1 D 30,79
Previous and Unofficial Names Click here for help
neuroendocrine L-type Ca2+ channel | α1D | CACH3 | CACN4 | CACNL1A2 | CCHL1A2 | calcium channel alpha-1 subunit | Cchl1a | calcium channel
Database Links Click here for help
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
β
α 25,34-35,52,63,79
Other Associated Proteins
Name References
erbin 11
Shank 82
Densin 31
Rab3 interacting molecule (RIM) 20
RIM binding proteins 26
pp60 (c-src) 70
bestrophin 81
calcium binding proteins 1, 2 14,60
calmodulin 17,77
RGK protein family members 9
whirlin 32
harmonin 23-24
otoferlin 55
retinoschisin 64
A-kinase anchoring proteins (15, MAP2B) 41
ankyrin 15
RyR2 33
Functional Characteristics Click here for help
L-type calcium current: more negative activation voltage range than Cav1.2, calcium-dependent inactivation
Ion Selectivity and Conductance Click here for help
Species:  Human
Single channel conductance (pS):  14.9-16.1 (15 mM Ba2+)
References:  5
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -20.0 - 79 Xenopus laevis oocyte Rat
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -39.0 – -1.3 (median: -28.4) 1.2 – 4.5 25,54,63,68,79 HEK-293, tsA-201 Rat
Inactivation  -58.8 – -33.5 (median: -35.4) 6.8 – 71.0 54,63
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -19.6 – 15.0 0.3 6,44,50 Cochlear outer and inner hair cells Mouse
Inactivation  -25.0 10.0 – 200.0 22,44
Comments  Activation thresholds at physiological extracellular calcium concentrations are between -50 and -65mV. ICa is mostly (>90%) Cav1.3 current [44,50].

Inactivation parameters are for outer hair cells only, as inactivation is much slower in inner hair cells [44].
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -19.3 – 26.5 0.3 22,68 Cochlear inner hair cells Rat
Inactivation  - -
Comments  Calcium-dependent inactivation is present in IHCs but the overall inactivation process is slower than in Cav1.3 currents in other tissues (e.g. sinoatrial node cells [39]).
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -20.2 – -2.2 (median: -12.9) 0.5 – 2.5 35-36,65 HEK-293, tsA-201 Human
Inactivation  -42.7 3.8 – 74.0 35,65
Comments  Data are for 15 mM Ba2+ or Ca2+. Activation and inactivation parameters differ between two different C-terminal splice variants (long and short forms; [65]).
Voltage Dependence Comments
Data are given for both Ca2+ and Ba2+ as the charge carrier. V0.5 for activation is higher with Ca2+ as a charge carrier than with Ba2+ (but more negative than for Cav1.2 under identical experimental conditions; [79]).

Activation and inactivation parameters differ between different C-terminal splice variants (long and several short forms; [5,37,65,72]). Short forms lack a C-terminal modulatory domain which reduces calcium-dependent inactivation and reduces voltage-sensitivity.

Inactivation time course depends on associated β subunit (slower with β2), C-terminal splice variant and on charge carrier (pronounced calcium-induced inactivation with Ca2+; [65]).

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
BAYK 8644 Small molecule or natural product Click here for species-specific activity table Hs - - - 5x10-6 -90.0 – -83.0 35,50
Conc range: 5x10-6 M [35,50]
Holding voltage: -90.0 – -83.0 mV
BAYK 8644 Small molecule or natural product Click here for species-specific activity table Rn - - - 1x10-6 -80.0 79
Conc range: 1x10-6 M [79]
Holding voltage: -80.0 mV
FPL64176 Small molecule or natural product Click here for species-specific activity table Hs - ~7.8 pEC50 - -
pEC50 ~7.8 (EC50 ~1.6x10-8 M)
(-)-(S)-BayK8644 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs - ~7.8 pEC50 - -
pEC50 ~7.8 (EC50 ~1.73x10-8 M)
View species-specific activator tables
Activator Comments
Using rat channels, BAYK 8644 (1μM) shifted the V0.5 towards a more hyperpolarised voltage (-32.2mV to -39.0mV) [79].
Gating inhibitors Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
isradipine Small molecule or natural product Approved drug Click here for species-specific activity table Hs - - - 3x10-8 - 3x10-7 -90.0 – -50.0 35
Conc range: 3x10-8 - 3x10-7 M [35]
Holding voltage: -90.0 – -50.0 mV
[3H](+)-isradipine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs - 9.4 pKd - - 35
pKd 9.4 [35]
azidopine Small molecule or natural product Hs Inhibition 9.2 pIC50 - - 67
pIC50 9.2 (IC50 6.5x10-10 M) [67]
Description: Recombinant Cav1.3 calcium channel complexes expressed in tsA201-cells
isradipine Small molecule or natural product Approved drug Click here for species-specific activity table Hs - 7.8 – 9.3 pIC50 - - 48,67
pIC50 9.3 (IC50 5.1x10-10 M) [67]
Description: Recombinant Cav1.3 calcium channel complexes expressed in tsA201-cells
pIC50 7.8 – 8.2 dopamine neuron-like activity; splice variant-dependent [48]
nitrendipine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 - - 67
pIC50 8.4 (IC50 3.59x10-9 M) [67]
Description: Recombinant Cav1.3 calcium channel complexes expressed in tsA-cells
nifedipine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.7 pIC50 - - 67
pIC50 7.7 (IC50 2.01x10-8 M) [67]
Description: Recombinant Cav1.3 calcium channel complexes expressed in tsA-cells
amlodipine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.2 pIC50 - - 67
pIC50 7.2 (IC50 6.01x10-8 M) [67]
Description: Recombinant Cav1.3 calcium channel complexes expressed in tsA-cells
nisoldipine Small molecule or natural product Approved drug Click here for species-specific activity table Mm - 6.4 – 7.0 pIC50 - -80.0 78
pIC50 6.4 – 7.0 [78]
Holding voltage: -80.0 mV
nimodipine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 5.7 – 6.6 pIC50 - -80.0 – -40.0 56,79
pIC50 5.7 – 6.6 [56,79]
Holding voltage: -80.0 – -40.0 mV
View species-specific gating inhibitor tables
Gating Inhibitor Comments
Inhibition by dihydropyridines (e.g. isradipine [35,48]) is voltage-dependent with a higher apparent affinity at more depolarised voltage.
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
Cd2+ N/A Antagonist - - 2x10-4 -60.0 59
Conc range: 2x10-4 M [59]
Holding voltage: -60.0 mV
cinnarizine Small molecule or natural product Approved drug Ligand has a PDB structure Cp Pore blocker 5.8 pIC50 - -60.0 1
pIC50 5.8 [1]
Holding voltage: -60.0 mV
verapamil Small molecule or natural product Approved drug Click here for species-specific activity table Mm Antagonist 3.7 pIC50 - -70.0 73
pIC50 3.7 [73]
Holding voltage: -70.0 mV
diltiazem Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Mm - 3.5 pIC50 - -70.0 73
pIC50 3.5 [73]
Holding voltage: -70.0 mV
View species-specific channel blocker tables
Channel Blocker Comments
Amlodopine, isradipine, nifedipine, nitrendipine, and nimodipineare examples of dihydropyridine calcium channel antagonists. Verapamil is a phenylalkylamine calcium channel blocker. Diltiazem is an example of a benzothiazepine calcium channel blocker. Cav1.3 is less sensitive to dihydropyridine antagonists than Cav1.2.
The Cryo-EM structure of the human Cav1.3 channel bound to cinnarizine revealed a direct pore blockade by the drug [80]. Cinnarizine also inhibits cardiac Cav1.2 L-type and T-type channels with submicromolar Ki values but its subtype selectivity remains unclear [13]. At present there is no robust evidence for Cav1.3-selective calcium channel blockers [18].
Immunopharmacology Comments
Cav1.3 and Cav1.4 are involved in CD8+ T cell survival and cytokine production [47].
Cell Type Associations
Immuno Cell Type:  T cells
References:  74
Tissue Distribution Click here for help
Adrenal cortex (zona glomerulosa)
Species:  Human
Technique:  Microarray analysis
References:  2,58
Atriventricular node, right atrial myocytes.
Species:  Human
Technique:  RT-PCR
References:  39
Brain (ubiquitious), spinal cord, dorsal root ganglion.
Species:  Human
Technique:  RT-PCR
References:  71
Lymphocytes.
Species:  Human
Technique:  RT-PCR, Western blotting
References:  69
Adrenal chromaffin cells.
Species:  Mouse
Technique:  RT-PCR
References:  40
Retinal neurons.
Species:  Mouse
Technique:  Immunohistochemistry
References:  8
Sinoatrial node pacemaker cells, right atrial myocytes
Species:  Mouse
Technique:  RT-PCR
References:  39
Lymphocytes.
Species:  Mouse
Technique:  RT-PCR, Western blotting
References:  3
Hair cells (cochlea: inner and outer).
Species:  Mouse
Technique:  RT-PCR, electrophysiology (absence of currents in knockout mice)
References:  7,44
Brain.
Species:  Mouse
Technique:  Radioligand binding.
References:  12
Pancreatic islets.
Species:  Mouse
Technique:  RT-PCR
References:  76
Atrial myocytes
Species:  Rat
Technique:  Immunocytochemistry
References:  54
Tissue Distribution Comments
The physiological role of Cav1.3 L-type channels for lymphocyte function is not well established. Additionally, in lymphocytes the presence of Cav1.3 α1 subunit protein has not yet been proven using Cav1.3-α1 deficient mice as negative controls; therefore the specificity of antibody staining remians questionable [10,69].
Functional Assays Click here for help
Patch-clamp (whole cell currents) recording from cells derived from Cav1.3 knockout mice.
Species:  Mouse
Tissue:  Cochlear hair cells
Response measured:  L-type currents.
References:  6-7,44,50
Patch-clamp (whole cell currents) recording from cells derived from Cav1.3 knockout mice.
Species:  Mouse
Tissue:  Sinoatrial node cells
Response measured:  L-type currents.
References:  39,83
Patch-clamp (whole cell currents) recording from HEK-293 cells transfected with Cav1.3.
Species:  Human
Tissue:  HEK-293 cells
Response measured:  L-type currents.
References:  35-36,68
Patch-clamp (whole cell currents) recording from HEK-293 cells transfected with Cav1.3.
Species:  Rat
Tissue:  HEK-293 cells
Response measured:  L-type currents
References:  25,54,56,63,79
Two-electrode voltage clamp recording from Xenopus oocytes transfected with Cav1.3.
Species:  Rat
Tissue:  Xenpous oocytes
Response measured:  L-type currents
References:  79
Whole cell patch-clamp
Species:  Mouse
Tissue:  Adrenal chromaffin cells
Response measured:  Calcium inward current
References:  40,75
Physiological Functions Click here for help
Sinoatrial node pacemaking.
Species:  Mouse
Tissue:  Heart.
References:  39,50,83
Hearing.
Species:  Mouse
Tissue:  Cochlea, inner ear.
References:  7,44,50
Brain (spontaneous neuronal activity).
Species:  Mouse
Tissue:  Medium spiny neurons.
References:  46
Brain function (consolidation of contextually conditioned fear; mood behaviour).
Species:  Mouse
Tissue:  Brain.
References:  42,66
Synaptic refinement in auditory brainstem
Species:  Mouse
Tissue:  Brain
References:  27
Fear memory consolidation, amygdala LTP
Species:  Mouse
Tissue:  Brain
References:  43
Long-term adaptation in dopamine D2L-mediated GluA1 trafficking in the dorsal striatum following cocaine exposure
Species:  Mouse
Tissue:  Brain
References:  57
Acquisition of psychostimulant-induced locomotor sensitization
Species:  Mouse
Tissue:  Brain
References:  21
Catacholamine secretion from adrenal chromaffin cells
Species:  Mouse
Tissue:  Adrenal chromaffin cells
References:  51
Physiological Consequences of Altering Gene Expression Click here for help
Sinus bradycardia and spontaneous arrhythmia
Species:  Mouse
Tissue:  Heart
Technique:  Knockout
References:  39,50,83
Congenital deafness
Species:  Mouse
Tissue:  Cochlea, inner ear
Technique:  Knockout
References:  7,44,50
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0004231 abnormal calcium ion homeostasis PMID: 11581302 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004231 abnormal calcium ion homeostasis PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004746 abnormal cochlear IHC afferent innervation pattern PMID: 12684182  14645476  16828974 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004633 abnormal cochlear IHC efferent innervation pattern PMID: 12684182  14645476  16828974 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004433 abnormal cochlear inner hair cell physiology PMID: 10929716  17074442 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004433 abnormal cochlear inner hair cell physiology PMID: 14645476  16828974 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004716 abnormal cochlear nerve morphology PMID: 12890513 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0004434 abnormal cochlear outer hair cell physiology PMID: 15357422 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004434 abnormal cochlear outer hair cell physiology PMID: 17074442 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004736 abnormal distortion product otoacoustic emission PMID: 17074442 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004562 abnormal inner hair cell synaptic ribbon morphology PMID: 16828974 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0009175 abnormal pancreatic beta cell differentiation PMID: 11581302 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0003562 abnormal pancreatic beta cell physiology PMID: 11581302 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0005215 abnormal pancreatic islet morphology PMID: 11581302 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0006142 abnormal sinoatrial node conduction PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004122 abnormal sinus arrhythmia PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004563 absent active-zone-anchored inner hair cell synaptic ribbon PMID: 12684182 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0004763 absent brainstem auditory evoked potential PMID: 15357422 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0004737 absent distortion product otoacoustic emissions PMID: 15357422 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0004530 absent outer hair cell stereocilia PMID: 15357422 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0006358 absent pinna reflex PMID: 11581302  15357422 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0006358 absent pinna reflex PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0006358 absent pinna reflex PMID: 12684182  12890513 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0010519 atrioventricular block PMID: 10929716 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0002857 cochlear ganglion degeneration PMID: 15357422 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0002857 cochlear ganglion degeneration PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0002857 cochlear ganglion degeneration PMID: 12684182  16828974 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004362 cochlear hair cell degeneration PMID: 12684182 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004398 cochlear inner hair cell degeneration PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004398 cochlear inner hair cell degeneration PMID: 12684182  12890513  16828974 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0004404 cochlear outer hair cell degeneration PMID: 15357422 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004404 cochlear outer hair cell degeneration PMID: 10929716  17074442 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004404 cochlear outer hair cell degeneration PMID: 12684182 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0001967 deafness PMID: 11581302  15357422 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0001967 deafness PMID: 10929716  17074442 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0001967 deafness PMID: 12684182 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0001262 decreased body weight PMID: 11581302 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0001262 decreased body weight PMID: 12890513 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0004765 decreased brainstem auditory evoked potential PMID: 11581302 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004765 decreased brainstem auditory evoked potential PMID: 10929716  17074442 
Cacna1d+|Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1d+
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0004765 decreased brainstem auditory evoked potential PMID: 15357422 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0002727 decreased circulating insulin level PMID: 11581302 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0005333 decreased heart rate PMID: 10929716 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0009114 decreased pancreatic beta cell mass PMID: 11581302 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0003339 decreased pancreatic beta cell number PMID: 11581302 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0009168 decreased pancreatic islet number PMID: 11581302 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0005293 impaired glucose tolerance PMID: 11581302 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0002891 increased insulin sensitivity PMID: 11581302 
Cacna1dtm1Hssh Cacna1dtm1Hssh/Cacna1dtm1Hssh
involves: 129S4/SvJae * C57BL/6J
MGI:88293  MP:0009176 increased pancreatic alpha cell number PMID: 11581302 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0003896 prolonged PR interval PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0010506 prolonged RR interval PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
involves: 129S7/SvEvBrd * C57BL/6J
MGI:88293  MP:0004740 sensorineural hearing loss PMID: 10929716 
Cacna1dtm1Jst Cacna1dtm1Jst/Cacna1dtm1Jst
B6.129S7-Cacna1d
MGI:88293  MP:0004740 sensorineural hearing loss PMID: 12684182 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Aldosterone-producing adenoma
Orphanet: ORPHA85142
Role: 
Comments: 
References:  2,49,58
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human V259D 2,58
Missense Human G403R exon 8A 2,58
Missense Human G403R exon 8B 2,58
Missense Human G403D exon 8B 2,58
Missense Human F747L 2
Missense Human I750M 2
Missense Human R990H 2
Missense Human P1336R 2
Missense Human M1354I 2
Disease:  Congenital hyperinsulinemic hypoglycemia
Description: Multiorgan disease, birth complications, hyperaldosteronism, hypertension
Role: 
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human L271H 16
Missense Human G403D exon 8B 19,58
Disease:  Neurodevelopmental disorder with autism
Disease Ontology: DOID:0012759
Role: 
Comments: 
References:  28,38,45,49
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human A769G 45
Disease:  Primary aldosteronism, seizures, and neurologic abnormalities; PASNA
Synonyms: Aldosterone-producing adenoma with seizures and neurological abnormalities [Orphanet: ORPHA369929]
OMIM: 615474
Orphanet: ORPHA369929
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human V259A 62
Missense Human L271H 16
Missense Human G403D 58
Missense Human I750M 58
Disease:  Sinoatrial node dysfunction and deafness; SANDD
OMIM: 614896
Orphanet: ORPHA324321
Role: 
References:  4,53
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Insertion Human c.1208_1209insGGG (in frame glycine insertion in IS6) 4
Clinically-Relevant Mutations and Pathophysiology Comments
Gain of function is shown for the somatic mutations causing aldosterone-producing adrenal adenomas, and for the germline mutations causing Congenital Hyperinsulinemic Hypoglycemia, Neurodevelopmental Abnormalities with Autism, and PASNA (for review see reference [49]).
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  Short C-terminal tail (does not contain C-terminal modulatory domain which affects channel gating). RNA sequence: EU363339 but with short exon 43 (Cav1.343S) or alternative exon 42A (Cav1.342A); this has the pharmacological effect of lowering sensitivity to dihydropyridine calcium channel blockers.
References:  5,29,48

References

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79. Xu W, Lipscombe D. (2001) Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J Neurosci, 21 (16): 5944-51. [PMID:11487617]

80. Yao X, Gao S, Yan N. (2022) Structural basis for pore blockade of human voltage-gated calcium channel Cav1.3 by motion sickness drug cinnarizine. Cell Res, 32 (10): 946-948. [PMID:35477996]

81. Yu K, Xiao Q, Cui G, Lee A, Hartzell HC. (2008) The best disease-linked Cl- channel hBest1 regulates Ca V 1 (L-type) Ca2+ channels via src-homology-binding domains. J Neurosci, 28 (22): 5660-70. [PMID:18509027]

82. Zhang H, Maximov A, Fu Y, Xu F, Tang TS, Tkatch T, Surmeier DJ, Bezprozvanny I. (2005) Association of CaV1.3 L-type calcium channels with Shank. J Neurosci, 25 (5): 1037-49. [PMID:15689539]

83. Zhang Z, Xu Y, Song H, Rodriguez J, Tuteja D, Namkung Y, Shin HS, Chiamvimonvat N. (2002) Functional Roles of Ca(v)1.3 (alpha(1D)) calcium channel in sinoatrial nodes: insight gained using gene-targeted null mutant mice. Circ Res, 90 (9): 981-7. [PMID:12016264]

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