CACNA1A
Domain
Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.
Function
Voltage-sensitive calcium channels (VSCC) 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, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are specifically blocked by the spider omega-agatoxin-IVA (AC P54282) (By similarity). They are however insensitive to dihydropyridines (DHP).
Involvement in disease
Spinocerebellar ataxia 6
SCA6
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA6 is an autosomal dominant cerebellar ataxia (ADCA), mainly caused by expansion of a CAG repeat in the coding region of CACNA1A. There seems to be a correlation between the repeat number and earlier onset of the disorder.
None
The disease is caused by variants affecting the gene represented in this entry.
Migraine, familial hemiplegic, 1
FHM1
A subtype of migraine with aura associated with ictal hemiparesis and, in some families, cerebellar ataxia and atrophy. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.
None
The disease is caused by variants affecting the gene represented in this entry.
Episodic ataxia 2
EA2
An autosomal dominant disorder characterized by acetozolamide-responsive attacks of ataxia, migraine-like symptoms, interictal nystagmus, and cerebellar atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Developmental and epileptic encephalopathy 42
DEE42
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE42 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1A subfamily.
Tissue Specificity
Brain specific; mainly found in cerebellum, cerebral cortex, thalamus and hypothalamus. Expressed in the small cell lung carcinoma cell line SCC-9. No expression in heart, kidney, liver or muscle. Purkinje cells contain predominantly P-type VSCC, the Q-type being a prominent calcium current in cerebellar granule cells.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
CACH4, CACN3, CACNL1A4, CACNA1A, Voltage-dependent P/Q-type calcium channel subunit alpha-1A, Brain calcium channel I, Voltage-gated calcium channel subunit alpha Cav2.1, BI