CACNA1A gene
The CACNA1A gene provides instructions for making calcium channels essential for nerve cell communication, and variants in this gene are linked to several neurological disorders.
Normal Function
The CACNA1A gene provides instructions for making calcium channels, which transport positively charged calcium ions across cell membranes. These channels are key to generating and transmitting electrical signals and are involved in cell-to-cell communication, muscle contraction, and gene regulation.
The gene provides instructions for the alpha-1 subunit of the CaV2.1 calcium channel, which forms the pore for calcium flow. These channels are abundant in Purkinje cells and granule cells in the cerebellum, where they control the release of neurotransmitters. The gene also produces a protein called alpha1-ACT (α1ACT), a transcription factor that helps control gene activity and is important for the development of neurons.
Health Conditions Related to Genetic Changes
Episodic ataxia
Variants in the CACNA1A gene can cause episodic ataxia type 2 (EA2), characterized by episodes of poor coordination, balance issues, and involuntary eye movements (nystagmus). These are loss-of-function variants that reduce CaV2.1 channel function, impairing neurotransmitter release in the brain.
Familial hemiplegic migraine
Variants in CACNA1A are linked to familial hemiplegic migraine type 1 (FHM1), which involves migraines with aura, including temporary numbness or weakness on one side of the body (hemiparesis). These are gain-of-function variants that increase CaV2.1 channel activity, leading to excessive neurotransmitter release. Certain variants, such as S218L, can cause life-threatening brain swelling (cerebral edema) and coma following minor head trauma.
Spinocerebellar ataxia type 6
Spinocerebellar ataxia type 6 (SCA6) results from an expansion of the CAG trinucleotide repeat in the CACNA1A gene (ranging from 20 to more than 30 repeats). This expansion impairs the function of the α1ACT transcription factor, preventing the survival of Purkinje cells in the cerebellum and leading to progressive ataxia, nystagmus, and impaired speech (dysarthria).
Sporadic hemiplegic migraine
Sporadic hemiplegic migraine presents with signs identical to FHM1 but occurs in individuals with no family history. These variants are acquired during a person's lifetime and increase CaV2.1 channel activity.
19p13.13 deletion syndrome
Individuals with 19p13.13 deletion syndrome are often missing one copy of the CACNA1A gene. This deletion is associated with features including macrocephaly, tall stature, intellectual disability, seizures, and ataxia.
Other disorders
Variants in the CACNA1A gene can also cause a form of developmental and epileptic encephalopathy, characterized by repeated seizures, developmental delays, intellectual disability, and weak muscle tone (hypotonia).
Other Names for This Gene
- APCA
- brain calcium channel 1
- CAC1A_HUMAN
- CACNL1A4
- calcium channel, alpha 1A subunit
- calcium channel, L type, alpha-1 polypeptide, isoform 4
- calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
- CAV2.1
- HPCA
- SCA6
- Voltage-gated calcium channel subunit alpha Cav2.1