Variant "CACNA1A:c.1360G>A(p.Ala454Thr)"
Search result: 1 record
Variant information
Gene:
CACNA1A 
Variant:
CACNA1A:c.1360G>A(p.Ala454Thr) 
Genomic location:
chr19:13428124(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_023035.2:c.1360G>A(p.Ala454Thr)
protein_coding NM_000068.3:c.1360G>A(p.Ala454Thr)
protein_coding NM_001127221.1:c.1360G>A(p.Ala454Thr)
protein_coding NM_001174080.1:c.1360G>A(p.Ala454Thr)
protein_coding NM_001127222.1:c.1357G>A(p.Ala453Thr)
dbSNP ID:
rs41276886  
GWAS trait:
no data 
Modifier statisitcs
Record:
1 
Disorder:
1 
Reference:
1 
Effect type:
Expressivity(1)  
Modifier effect:
Altered sensorimotor symptoms(1)  
Detail：
  • Target disease:
    Migraine (DOID_6364)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered sensorimotor symptoms 
    Evidence:
    Pedigree analysis 
    Effect:
    That genetic variation in CACNA1A may be not only a cause but also a modifier of migraine phenotype.
    Reference:
    PMID20080591
    Title:
    A mutation in the first intracellular loop of CACNA1A prevents P/Q channel modulation by SNARE proteins and lowers exocytosis.
    Species studied:
    Human
    Abstract:
    Familial hemiplegic migraine (FHM)-causing mutations in the gene encoding the P/Q Ca(2+) channel alpha(1A) subunit (CACNA1A) locate to the pore and voltage sensor regions and normally involve gain-of-channel function. We now report on a mutation identified in the first intracellular loop of CACNA1A (alpha(1A(A454T))) that does not cause FHM but is associated with the absence of sensorimotor symptoms in a migraine with aura pedigree. Alpha(1A(A454T)) channels showed weakened regulation of voltage-dependent steady-state inactivation by Ca(V)beta subunits. More interestingly, A454T mutation suppressed P/Q channel modulation by syntaxin 1A or SNAP-25 and decreased exocytosis. Our findings reveal the importance of I-II loop structural integrity in the functional interaction between P/Q channel and proteins of the vesicle-docking/fusion machinery, and that genetic variation in CACNA1A may be not only a cause but also a modifier of migraine phenotype.