Incidental Mutation 'R1168:Cacna1a'
ID101332
Institutional Source Beutler Lab
Gene Symbol Cacna1a
Ensembl Gene ENSMUSG00000034656
Gene Namecalcium channel, voltage-dependent, P/Q type, alpha 1A subunit
SynonymsCacnl1a4, alpha1A, SCA6, nmf352, Ccha1a
MMRRC Submission 039241-MU
Accession Numbers
Is this an essential gene? Probably essential (E-score: 0.769) question?
Stock #R1168 (G1)
Quality Score225
Status Not validated
Chromosome8
Chromosomal Location84388440-84640246 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 84579501 bp
ZygosityHeterozygous
Amino Acid Change Isoleucine to Valine at position 1293 (I1293V)
Ref Sequence ENSEMBL: ENSMUSP00000112436 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000121390] [ENSMUST00000122053]
Predicted Effect probably damaging
Transcript: ENSMUST00000121390
AA Change: I1293V

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000112436
Gene: ENSMUSG00000034656
AA Change: I1293V

DomainStartEndE-ValueType
low complexity region 9 47 N/A INTRINSIC
Pfam:Ion_trans 99 373 1.5e-69 PFAM
Pfam:Ion_trans 488 727 1.2e-54 PFAM
Pfam:PKD_channel 578 721 6.6e-8 PFAM
low complexity region 920 959 N/A INTRINSIC
low complexity region 977 987 N/A INTRINSIC
low complexity region 1074 1093 N/A INTRINSIC
low complexity region 1143 1168 N/A INTRINSIC
Pfam:Ion_trans 1194 1472 4.9e-64 PFAM
Pfam:Ion_trans 1516 1773 2.8e-64 PFAM
Pfam:GPHH 1775 1844 5.6e-39 PFAM
Ca_chan_IQ 1899 1933 1.8e-12 SMART
AT_hook 2053 2065 2.02e0 SMART
low complexity region 2101 2113 N/A INTRINSIC
low complexity region 2153 2179 N/A INTRINSIC
low complexity region 2213 2236 N/A INTRINSIC
low complexity region 2253 2282 N/A INTRINSIC
low complexity region 2314 2325 N/A INTRINSIC
low complexity region 2342 2357 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000122053
AA Change: I1246V

PolyPhen 2 Score 0.061 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000114055
Gene: ENSMUSG00000034656
AA Change: I1246V

DomainStartEndE-ValueType
low complexity region 9 47 N/A INTRINSIC
Pfam:Ion_trans 91 314 4.5e-58 PFAM
PDB:4DEX|B 317 427 5e-45 PDB
Pfam:Ion_trans 476 668 6.4e-46 PFAM
Pfam:PKD_channel 530 675 7.7e-8 PFAM
low complexity region 873 912 N/A INTRINSIC
low complexity region 930 940 N/A INTRINSIC
low complexity region 1027 1046 N/A INTRINSIC
low complexity region 1096 1121 N/A INTRINSIC
Pfam:Ion_trans 1183 1414 2.8e-54 PFAM
Pfam:Ion_trans 1504 1714 3.2e-60 PFAM
Ca_chan_IQ 1852 1886 1.8e-12 SMART
AT_hook 2006 2018 2.02e0 SMART
low complexity region 2054 2066 N/A INTRINSIC
low complexity region 2106 2132 N/A INTRINSIC
low complexity region 2166 2189 N/A INTRINSIC
low complexity region 2206 2235 N/A INTRINSIC
low complexity region 2267 2278 N/A INTRINSIC
low complexity region 2295 2310 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000126302
Predicted Effect unknown
Transcript: ENSMUST00000215756
AA Change: I1245V
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.1%
  • 10x: 95.2%
  • 20x: 88.8%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]
PHENOTYPE: Homozygotes for different mutant alleles are characterized by variably severe wobbly gait beginning prior to weaning, ataxia, episodic dyskinesia, cerebellar atrophy, and absence epilepsy. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 80 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110002E22Rik T C 3: 138,067,900 V950A probably benign Het
4930452B06Rik T C 14: 8,442,939 N610S probably benign Het
Adgrb3 A T 1: 25,826,199 S188T probably benign Het
Ahr A T 12: 35,504,532 N529K possibly damaging Het
Akr1c21 A G 13: 4,583,837 N302D probably benign Het
Aldh8a1 T A 10: 21,384,631 probably null Het
Alpk3 A T 7: 81,103,357 K1554M probably damaging Het
Arhgef5 T A 6: 43,273,396 H360Q probably benign Het
Cacna2d4 C T 6: 119,307,286 R745W probably damaging Het
Cd200r4 T A 16: 44,832,944 W72R probably damaging Het
Ces2e A T 8: 104,927,014 D28V possibly damaging Het
Cfap45 T C 1: 172,545,697 Y534H probably damaging Het
Cfap54 A T 10: 92,937,920 C87S probably damaging Het
Chmp7 C T 14: 69,719,450 M336I probably benign Het
Chrna4 T A 2: 181,034,138 M67L possibly damaging Het
Cts7 T A 13: 61,353,817 N290Y probably damaging Het
Enpp6 A T 8: 47,030,454 M94L probably damaging Het
Fam83d C T 2: 158,768,523 A137V probably benign Het
Foxd2 C T 4: 114,907,678 A382T possibly damaging Het
Galnt11 T G 5: 25,250,246 S193R probably damaging Het
Gapvd1 A T 2: 34,704,469 D856E probably damaging Het
Gclm T A 3: 122,262,688 H86Q possibly damaging Het
Gipc2 T C 3: 152,107,997 T220A probably benign Het
Gm12185 G T 11: 48,915,355 N336K possibly damaging Het
Gm5431 A T 11: 48,895,364 S61R probably benign Het
Gm884 T C 11: 103,618,950 probably benign Het
Gorasp2 C T 2: 70,688,400 P260S probably damaging Het
H2-M10.6 A G 17: 36,813,160 Q172R probably benign Het
Ibsp A G 5: 104,302,152 I6V probably damaging Het
Iqsec1 T C 6: 90,689,676 Y593C probably damaging Het
Itln1 G T 1: 171,531,551 Y61* probably null Het
Kif21a G A 15: 90,993,753 T284I probably damaging Het
Kif3a G A 11: 53,598,312 G621R probably damaging Het
Klb A G 5: 65,378,974 Y549C probably damaging Het
Lman1l G A 9: 57,608,312 R427C probably benign Het
Map4 T C 9: 110,034,964 V419A probably benign Het
Mastl A T 2: 23,133,132 D526E probably benign Het
Mrvi1 T C 7: 110,895,931 K429R probably damaging Het
Mtif2 A G 11: 29,536,914 D308G probably benign Het
Ncald A G 15: 37,397,334 F34S probably damaging Het
Ndc1 A G 4: 107,395,812 T593A probably benign Het
Ndst3 C T 3: 123,606,968 V15I probably benign Het
Nup214 A G 2: 32,025,301 N1166D probably benign Het
Olfr1031 A T 2: 85,992,684 Y289F probably damaging Het
Olfr1240 G A 2: 89,439,869 Q137* probably null Het
Olfr1368 A G 13: 21,142,617 S147P probably benign Het
Olfr403 A G 11: 74,196,421 H306R probably benign Het
Pcdhb8 T C 18: 37,356,727 I486T probably benign Het
Pdzrn4 A T 15: 92,770,271 Y768F probably benign Het
Pgf A G 12: 85,171,767 S70P probably benign Het
Plcl2 G A 17: 50,607,072 A370T possibly damaging Het
Pnkp T A 7: 44,862,537 W115R probably benign Het
Ppp1r16a C T 15: 76,693,669 Q328* probably null Het
Prag1 A G 8: 36,146,645 E1117G probably damaging Het
Prr12 T A 7: 45,029,047 Q1919L unknown Het
Ret G T 6: 118,173,558 H666N possibly damaging Het
Rfwd3 C T 8: 111,288,242 R326Q probably damaging Het
Robo2 C T 16: 73,948,296 G864S probably damaging Het
Rpa2 T G 4: 132,771,860 I80S probably damaging Het
Ryk A T 9: 102,898,475 D428V probably damaging Het
Slc29a1 A T 17: 45,590,278 N30K probably damaging Het
Stbd1 A G 5: 92,604,936 N95S probably benign Het
Tbc1d22a A G 15: 86,292,134 E212G probably benign Het
Tex14 A G 11: 87,536,742 T7A probably benign Het
Tmc8 T C 11: 117,792,563 V648A possibly damaging Het
Tmem132b G T 5: 125,787,019 V730F probably damaging Het
Tmub2 G A 11: 102,287,370 G33D possibly damaging Het
Trak1 G A 9: 121,440,679 D124N probably damaging Het
Ttc28 A T 5: 111,231,111 Y1154F probably damaging Het
Ttn T C 2: 76,909,369 T3609A probably benign Het
Tulp2 A G 7: 45,517,842 T99A probably benign Het
Ugt2a2 A T 5: 87,465,568 probably null Het
Ush2a G A 1: 188,678,411 V2419I probably benign Het
Vill C A 9: 119,070,321 P343Q probably damaging Het
Vmn2r66 T A 7: 85,006,854 H318L possibly damaging Het
Wdr3 A C 3: 100,142,219 N800K probably benign Het
Wdr93 A G 7: 79,749,174 K19E probably damaging Het
Wrn A G 8: 33,316,408 S333P probably damaging Het
Zfp418 T C 7: 7,182,501 S488P possibly damaging Het
Zfp804a A G 2: 82,256,697 E290G probably benign Het
Other mutations in Cacna1a
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00507:Cacna1a APN 8 84571208 nonsense probably null
IGL00513:Cacna1a APN 8 84553056 missense probably damaging 1.00
IGL00569:Cacna1a APN 8 84462714 missense probably damaging 1.00
IGL00981:Cacna1a APN 8 84548553 missense probably damaging 1.00
IGL01122:Cacna1a APN 8 84614793 critical splice donor site probably null
IGL01309:Cacna1a APN 8 84523028 missense probably damaging 1.00
IGL01380:Cacna1a APN 8 84559117 missense probably damaging 1.00
IGL01638:Cacna1a APN 8 84571827 missense probably damaging 0.98
IGL01682:Cacna1a APN 8 84536438 missense possibly damaging 0.71
IGL02751:Cacna1a APN 8 84569952 missense probably damaging 1.00
IGL02904:Cacna1a APN 8 84579520 missense probably damaging 1.00
IGL03122:Cacna1a APN 8 84462676 splice site probably benign
totter UTSW 8 84588753 missense probably damaging 0.99
totter2 UTSW 8 84588753 missense probably damaging 0.99
FR4340:Cacna1a UTSW 8 84638723 small insertion probably benign
FR4449:Cacna1a UTSW 8 84638714 small insertion probably benign
FR4449:Cacna1a UTSW 8 84638720 small insertion probably benign
FR4449:Cacna1a UTSW 8 84638723 small insertion probably benign
FR4548:Cacna1a UTSW 8 84638717 small insertion probably benign
FR4737:Cacna1a UTSW 8 84638720 small insertion probably benign
FR4737:Cacna1a UTSW 8 84638726 small insertion probably benign
FR4976:Cacna1a UTSW 8 84638717 small insertion probably benign
FR4976:Cacna1a UTSW 8 84638726 small insertion probably benign
IGL03134:Cacna1a UTSW 8 84559087 missense probably damaging 1.00
R0055:Cacna1a UTSW 8 84580058 splice site probably benign
R0118:Cacna1a UTSW 8 84536083 missense probably damaging 1.00
R0284:Cacna1a UTSW 8 84612285 missense probably damaging 1.00
R0581:Cacna1a UTSW 8 84601936 missense possibly damaging 0.83
R0607:Cacna1a UTSW 8 84629831 missense probably damaging 1.00
R1183:Cacna1a UTSW 8 84580217 missense probably damaging 1.00
R1470:Cacna1a UTSW 8 84514950 splice site probably benign
R1503:Cacna1a UTSW 8 84601946 missense probably benign 0.23
R1522:Cacna1a UTSW 8 84633433 missense probably benign 0.00
R1835:Cacna1a UTSW 8 84581357 splice site probably null
R1862:Cacna1a UTSW 8 84415930 missense possibly damaging 0.80
R2148:Cacna1a UTSW 8 84629675 missense possibly damaging 0.71
R2237:Cacna1a UTSW 8 84633765 critical splice donor site probably null
R2567:Cacna1a UTSW 8 84549725 missense probably damaging 1.00
R2999:Cacna1a UTSW 8 84567742 missense probably damaging 1.00
R3025:Cacna1a UTSW 8 84580225 critical splice donor site probably null
R3610:Cacna1a UTSW 8 84559065 missense probably damaging 1.00
R3702:Cacna1a UTSW 8 84617846 missense probably damaging 0.98
R3763:Cacna1a UTSW 8 84583642 missense possibly damaging 0.85
R4025:Cacna1a UTSW 8 84581333 missense probably damaging 1.00
R4026:Cacna1a UTSW 8 84581333 missense probably damaging 1.00
R4106:Cacna1a UTSW 8 84583695 missense possibly damaging 0.85
R4296:Cacna1a UTSW 8 84559293 missense probably damaging 1.00
R4664:Cacna1a UTSW 8 84601767 nonsense probably null
R4713:Cacna1a UTSW 8 84549514 missense probably damaging 1.00
R5223:Cacna1a UTSW 8 84587195 missense possibly damaging 0.94
R5408:Cacna1a UTSW 8 84549707 missense probably damaging 1.00
R5644:Cacna1a UTSW 8 84462777 missense probably damaging 1.00
R5734:Cacna1a UTSW 8 84583731 missense probably damaging 0.96
R5786:Cacna1a UTSW 8 84415721 unclassified probably benign
R5833:Cacna1a UTSW 8 84518697 missense probably damaging 1.00
R5886:Cacna1a UTSW 8 84523022 missense probably damaging 0.99
R6049:Cacna1a UTSW 8 84638846 missense probably damaging 0.96
R6054:Cacna1a UTSW 8 84556785 missense probably damaging 0.99
R6117:Cacna1a UTSW 8 84614721 missense probably damaging 1.00
R6149:Cacna1a UTSW 8 84569952 missense probably damaging 1.00
R6195:Cacna1a UTSW 8 84588753 missense probably damaging 0.99
R6233:Cacna1a UTSW 8 84588753 missense probably damaging 0.99
R6607:Cacna1a UTSW 8 84579492 missense probably damaging 1.00
R6753:Cacna1a UTSW 8 84580205 missense probably damaging 1.00
R6798:Cacna1a UTSW 8 84611602 missense probably damaging 1.00
R6831:Cacna1a UTSW 8 84571231 missense probably damaging 1.00
X0022:Cacna1a UTSW 8 84633699 missense possibly damaging 0.53
Predicted Primers
Posted On2014-01-15