PhenoModifier-Gene Detail

Gene "CACNA1A"

Found 1 record

Gene information

Gene symbol:

CACNA1A

See related:

Ensembl: ENSG00000141837, Gene ID: 773

Additive variants :

Detected

Genetic interaction partners

Confidence	Stringent (ε>0.16 or ε<-0.12)	Intermediate (-0.16≤ε≤-0.08 or 0.08≤ε≤0.16)	Lenient (\|ε\|<0.08)
Positive interactions	DNAJA4 EIF2B1 PC XPO5 PFDN6 HNRNPM MRTO4 DDX59 MAPKAPK5 DMC1 CFDP1 DOT1L CHCHD2 PDCD6IP ANKRD55 COQ7 ELOF1 PQLC2L FHIT TSSK3 BRSK1 RPS6 XRCC3 TRMT44 PDHB MAF1 PDHA2 RFX4 AP2A2 ACTR6 WWOX MSH5-SAPCD1 SNX10 USP10 VPS13D RPS11 CHIA SIN3A SLC25A35 OLA1 DPH2 SCP2 PPAN HEMK1 PPIP5K1 TBC1D20 SRR MAPK11 D2HGDH APIP MLH1 DPP6 RBKS GPCPD1 GPD2 MAD2L1 LSM1 ROMO1 KMO GET4 SLC36A1 MELK PPIAL4A H3F3C show allhide
Negative interactions	XPC GGPS1 FA2H TGS1 RANGRF DDX31 TUSC3 ARHGAP35 SAC3D1 BUD31 RPS24 TBL1XR1 AZIN2 NAA30 GPT RAB6B XRN1 RPS29 YME1L1 CWH43 SUB1 UBA52 RCOR1 MOGS ARHGAP29 RPL14 ALPL RPL8 PFKFB2 ALG5 GOLPH3L SLC30A8 MRI1 SLC25A1 TRIT1 GLIPR2 DBR1 PUS7L MAP3K2 GLRX2 GYG1 MAEA SNX7 ARIH1 EPS15 CRY2 RPL35 GK5 NKTR MBOAT4 TSR3 MECOM LSM14B THUMPD1 ABCC5 ATG5 REXO2 FAU EEF1A2 ATP7B TXNL1 SH3YL1 SLC38A7 PEX12 NAALAD2 RPS6KA1 ARHGAP29 NGLY1 PIAS1 CNN3 PPAT PIGG IPO9 show allhide

Modifier statisitcs

Record:

Disorder:

Vriant:

Reference:

Effect type:

Expressivity(1)

Modifier effect:

Altered sensorimotor symptoms(1)

Detail：

Variant 1:

CACNA1A:c.1360G>A(p.Ala454Thr)

Gene:

CACNA1A

Genomic location:

chr19:13428124

dbSNP ID:

rs41276886

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.