CACNA1H Gene
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CACNA1H Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CACNA1H</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Calcium Voltage-Gated Channel Subunit Alpha1 H</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>16p13.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>8916</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000118260</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>O43480</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Association Type</td>
</tr>
<tr>
<td class="label">Childhood Absence Epilepsy</td>
<td>Causative</td>
</tr>
<tr>
<td class="label">Autism Spectrum Disorder</td>
<td>Risk Modulator</td>
</tr>
<tr>
<td class="label">[Alzheimer's Disease](/diseases/alzheimers-disease)</td>
<td>Risk Modulator</td>
</tr>
<tr>
<td class="label">Major Depression</td>
<td>Risk Modifier</td>
</tr>
<tr>
<td class="label">Drug/Compound</td>
<td>Type</td>
</tr>
<tr>
<td class="label">Ethosuximide</td>
<td>Small molecule</td>
</tr>
<tr>
<td class="label">VPA</td>
<td>Small molecule</td>
</tr>
<tr>
<td class="label">Zonisamide</td>
<td>Small molecule</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Type</td>
</tr>
<tr>
<td class="label">Ethosuximide</td>
<td>T-type blocker</td>
</tr>
<tr>
<td class="label">Z944</td>
<td>T-type blocker</td>
</tr>
<tr>
<td class="label">Valproic acid</td>
<td>Broad-spectrum</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Cacna1H Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
Cacna1H Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@jahromi2019]
Gene Overview
CACNA1H (Calcium Voltage-Gated Channel Subunit Alpha1 H) encodes the α1H subunit of voltage-gated calcium channels, forming the pore of the T-type (CaV3.2) calcium channel. [@saito2015]
Function
The CACNA1H gene encodes the α1H subunit that forms the pore of the T-type calcium channel (CaV3.2). This channel is characterized by:
- Low-voltage activation: Activates near -60 mV
- Rapid activation and inactivation: Fast kinetics
- Wide neuronal expression: Throughout the CNS
- Dendritic localization: Contributes to dendritic calcium signals
T-type channels are essential for:
- Burst firing in thalamic and cortical [neurons](/entities/neurons)
- Low-threshold calcium spike generation
- Pacemaker activity
- Sleep and arousal states
Disease Associations
Key Variants
- R902C: Gain-of-function causing epilepsy
- D1463N: Associated with increased seizure susceptibility
- P1090L: Variant found in ASD patients
Expression Pattern
CACNA1G shows broad expression:
- [Cortex](/brain-regions/cortex): All layers, particularly layer 5
- Thalamus: Moderate expression
- [Hippocampus](/brain-regions/hippocampus): CA1-CA3, dentate gyrus
- Cerebellum: Purkinje cells
- Brainstem: Various nuclei
Therapeutic Targeting
Key Publications
CACNA1H in epilepsy - Khosravani H, et al. J Clin Invest 2004 PMID: 15503460(https://pubmed.ncbi.nlm.nih.gov/15503460/)
T-type channels in cortex - Jahromi SS, et al. Cereb Cortex 2019 PMID: 30629144(https://pubmed.ncbi.nlm.nih.gov/30629144/)See Also
- [Voltage-Gated Calcium Channels](/mechanisms/voltage-gated-calcium-channels)mechanisms/ion-channel-dysfunction-neurodegeneration)
- [Calcium Signaling in Neurodegeneration](/mechanisms/calcium-dysregulation)
- [Cav3.2 Protein](/proteins/cav3-2-protein)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Epilepsy](/diseases/epilepsy)
External Links
- [NCBI Gene: CACNA1H](https://www.ncbi.nlm.nih.gov/gene/8916)
- [UniProt: CACNA1H](https://www.uniprot.org/uniprot/O43480)
Overview
Cacna1H Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Cacna1H Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Expression Pattern
CACNA1H encodes the T-type calcium channel Cav3.2, showing widespread expression:
- Brain: Thalamus, hippocampus, cerebral cortex, cerebellum
- Heart: Cardiac sinoatrial and atrioventricular nodes
- Kidney: Renal tubules
- Adrenal gland: Zona glomerulosa
- Peripheral tissues: Various endocrine organs
In neurons, Cav3.2 channels are critical for pacemaking and burst firing.
Channel Properties
Biophysical Characteristics
- Low-voltage activation: Activates at relatively negative potentials
- Rapid inactivation: Fast decay during sustained depolarization
- Rebound depolarization: Supports low-threshold calcium spikes
- Window current: Contributes to resting calcium influx
Subcellular Localization
- Somatic membrane: Cell body expression
- Dendritic shafts: Back-propagation of action potentials
- Axon initial segment: Regulates action potential initiation
- Presynaptic terminals: Modulates neurotransmitter release
Disease Associations
Childhood Absence Epilepsy
CACNA1H mutations are associated with childhood absence epilepsy:
- Gain-of-function variants increase neuronal excitability
- Thalamic filtering abnormalities
- 3 Hz spike-and-wave discharges
Alzheimer's Disease
In AD, CACNA1H contributes to:
- Calcium dysregulation in neurons
- Amyloid-beta effects on channel function
- Synaptic plasticity impairment
- Neuronal vulnerability
Parkinson's Disease
T-type channels in PD:
- Dopaminergic neuron pacemaking
- Levodopa-induced dyskinesias
- Therapeutic target potential
Therapeutic Targeting
Key Publications
Referenc
Brain Atlas Resources
- Allen Human Brain Atlas: [Gene expression search](https://human.brain-map.org/microarray/search/show?search_term=CACNA1H)
- Allen Mouse Brain Atlas: [Gene search](https://mouse.brain-map.org/search/index.html?query=CACNA1H)
- Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
- BrainSpan Developmental Transcriptome: [Developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=CACNA1H)
References
[Khosravani H, et al, J Clin Invest 2004;114:912-922 (2004)](https://pubmed.ncbi.nlm.nih.gov/15546003/)
[Jahromi SS, et al, Cereb Cortex 2019;29:3834-3847 (2019)](https://pubmed.ncbi.nlm.nih.gov/30629144/)
[Saito Y, et al, Brain Dev 2015;37:783-789 (2015)](https://pubmed.ncbi.nlm.nih.gov/25662842/)
[Chen Y, et al, PLoS One 2013;8:e82491 (2013)](https://pubmed.ncbi.nlm.nih.gov/24349281/)
[Lu YH, et al, Sci Rep 2018;8:16887 (2018)](https://pubmed.ncbi.nlm.nih.gov/30442957/)
[Wang G, et al, Cell Calcium 2017;61:41-48 (2017)](https://pubmed.ncbi.nlm.nih.gov/28063538/)
[Huang H, et al, Neuropharmacology 2017;118:49-61 (2017)](https://pubmed.ncbi.nlm.nih.gov/28232295/)
[Wang J, et al, J Neurosci 2019;39:5937-5950 (2019)](https://pubmed.ncbi.nlm.nih.gov/31085601/)Pathway Diagram
The following diagram shows the key molecular relationships involving CACNA1H Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)