CACNA1A (calcium voltage-gated channel subunit alpha1 A)
- symbol:
- CACNA1A
- locus group:
- protein-coding gene
- location:
- 19p13.13
- gene_family:
- Calcium channels, voltage-dependent
- alias symbol:
- Cav2.1|EA2|APCA|HPCA|FHM
- alias name:
- None
- entrez id:
- 773
- ensembl gene id:
- ENSG00000141837
- ucsc gene id:
- uc002mwy.5
- refseq accession:
- NM_000068
- hgnc_id:
- HGNC:1388
- approved reserved:
- 1996-06-18
CACNA1A基因编码电压门控钙通道的α1A亚基（Cav2.1），属于钙离子通道基因家族（voltage-gated calcium channels, VGCCs）。该家族通过调控钙离子内流参与神经递质释放、肌肉收缩等重要生理过程。CACNA1A主要在神经系统高表达，尤其小脑皮层和突触前膜，其表达的P/Q型钙通道通过介导动作电位触发的钙内流调控神经递质释放。该基因突变可导致多种神经系统疾病：错义突变引发家族性偏瘫型偏头痛（FHM1），表现为剧烈头痛伴运动障碍；C末端扩增突变引起脊髓小脑共济失调6型（SCA6），导致进行性运动协调障碍；无义突变则与发作性共济失调2型（EA2）相关，表现为间歇性平衡失调。基因过表达可能增强神经元兴奋性，但会破坏钙稳态引发兴奋毒性；表达降低则损害突触传递，导致运动障碍。该基因与CACNA1B、CACNA1C等同属VGCC家族，成员均含4个同源结构域，每个结构域含6个跨膜片段，通过电压敏感区域感知膜电位变化。值得注意的是，CACNA1A突变产生的通道功能异常具有双向性：功能增益型突变（如FHM1）增加钙电流，而功能丧失型突变（如EA2）减少电流，这种矛盾现象源于不同突变对通道门控特性的差异化影响。最新研究发现其与癫痫、阿尔茨海默病也存在关联，可能通过影响β淀粉样蛋白生成途径发挥作用。
Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-16 to 21-28 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Mar 2010]
电压依赖性钙通道介导的钙离子进入可兴奋细胞，并也参与多种钙依赖性过程，包括肌肉收缩，激素或神经递质释放和基因表达的。钙通道是α-1，β，α-2 /三角，和γ亚单位组成多亚基复合物。信道活动由孔形成的α-1亚单位指示，而，其他的作为辅助亚基调节此活动。钙通道类型的独特性质主要涉及多种α-1同种型，α-1A，B，C，D，E，和S这种基因的表达编码α-1A亚基，这主要是在神经组织??中表达。在这种基因突变与2神经系统疾病，家族性偏瘫性偏头痛和发作性共济失调2，该基因也显示出多晶型的变化，由于（CAG）正 - 重复相关联。已发现该基因编码不同亚型的多个抄本变形。在一组转录变体中，（CAG）的正 - 重复发生在3‘端非编码区，并且不与任何疾病相关。但在另一组变体，插入延伸的编码区，以包括（CAG）正 - 重复序列，其编码一个多聚谷氨酰胺道。在（CAG）的扩展，从正常的4-1正重复6中的编码区21-28与[由RefSeq的，2010年3月提供]脊髓小脑性共济失调6相关联
基因本体信息
CACNA1A基因（以及对应的蛋白质）的细胞分布位置：
- 质膜
- 细胞质
- 细胞外
- 高尔基体
- 囊泡
- 细胞骨架
- 内质网
- 细胞核
- 内体
- 溶酶体
- 线粒体
CACNA1A基因的本体（GO）信息：
| 名称 |
|---|
| 4010 MAPK signaling pathway [PATH:hsa04010] |
| 4020 Calcium signaling pathway [PATH:hsa04020] |
| 4724 Glutamatergic synapse [PATH:hsa04724] |
| 4727 GABAergic synapse [PATH:hsa04727] |
| 4725 Cholinergic synapse [PATH:hsa04725] |
| 4728 Dopaminergic synapse [PATH:hsa04728] |
| 4726 Serotonergic synapse [PATH:hsa04726] |
| 4730 Long-term depression [PATH:hsa04730] |
| 4723 Retrograde endocannabinoid signaling [PATH:hsa04723] |
| 4721 Synaptic vesicle cycle [PATH:hsa04721] |
| 4742 Taste transduction [PATH:hsa04742] |
| 5032 Morphine addiction [PATH:hsa05032] |
| 5033 Nicotine addiction [PATH:hsa05033] |
| 4930 Type II diabetes mellitus [PATH:hsa04930] |
| 名称 |
|---|
| Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels |
| Integration of energy metabolism |
| Metabolism |
| Neuronal System |
| Regulation of insulin secretion |
| Transmission across Chemical Synapses |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Episodic ataxia type 2 (disorder) | 0.5751248 | 55 | 32 | BeFree_CLINVAR_CTD_human_GAD_MGD_ORPHANET_UNIPROT |
| Spinocerebellar Ataxia Type 6 (disorder) | 0.4551248 | 50 | 6 | BeFree_CLINVAR_GAD_MGD_ORPHANET_UNIPROT |
| Hemiplegic migraine, familial type 1 | 0.331672 | 47 | 17 | BeFree_CTD_human_MGD_UNIPROT |
| Exfoliation Syndrome | 0.240271442 | 1 | 1 | BeFree_CTD_human_GWASCAT |
| Absence Epilepsy | 0.201628651 | 6 | 0 | BeFree_CTD_human_RGD |
| Ataxia, Spinocerebellar | 0.150157299 | 27 | 0 | BeFree_CTD_human_GAD_LHGDN |
| Ataxia | 0.142493457 | 38 | 2 | BeFree_CTD_human_GAD_LHGDN |
| MIGRAINE, SPORADIC HEMIPLEGIC | 0.121900093 | 7 | 2 | BeFree_CLINVAR |
| Alternating hemiplegia of childhood | 0.120814326 | 3 | 0 | BeFree_ORPHANET |
| Epilepsy, Temporal Lobe | 0.08 | 1 | 0 | RGD |
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