Incidental Mutation 'R6117:Cacna1a'
ID 485161
Institutional Source Beutler Lab
Gene Symbol Cacna1a
Ensembl Gene ENSMUSG00000034656
Gene Name calcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Synonyms Cacnl1a4, Ccha1a, SCA6, alpha1A, smrl, nmf352
MMRRC Submission 044266-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.924) question?
Stock # R6117 (G1)
Quality Score 225.009
Status Not validated
Chromosome 8
Chromosomal Location 85065268-85366875 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 85341350 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 1804 (Y1804C)
Ref Sequence ENSEMBL: ENSMUSP00000112436 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000121390] [ENSMUST00000122053]
AlphaFold P97445
Predicted Effect probably damaging
Transcript: ENSMUST00000121390
AA Change: Y1804C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000112436
Gene: ENSMUSG00000034656
AA Change: Y1804C

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 damaging
Transcript: ENSMUST00000122053
AA Change: Y1757C

PolyPhen 2 Score 0.979 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000114055
Gene: ENSMUSG00000034656
AA Change: Y1757C

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: ENSMUST00000127527
Predicted Effect noncoding transcript
Transcript: ENSMUST00000141981
Predicted Effect noncoding transcript
Transcript: ENSMUST00000143215
Predicted Effect noncoding transcript
Transcript: ENSMUST00000144879
Predicted Effect noncoding transcript
Transcript: ENSMUST00000153691
Predicted Effect unknown
Transcript: ENSMUST00000215756
AA Change: Y1756C
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 98.3%
  • 20x: 95.4%
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: 45 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Agbl1 A G 7: 76,348,534 (GRCm39) Y625C probably damaging Het
Ankmy1 A G 1: 92,788,996 (GRCm39) probably benign Het
Apmap T C 2: 150,442,252 (GRCm39) T41A probably benign Het
Cacna1e A T 1: 154,437,537 (GRCm39) I333N possibly damaging Het
Cdsn C A 17: 35,865,931 (GRCm39) S153R unknown Het
Celsr1 A T 15: 85,816,612 (GRCm39) M1777K probably benign Het
Cmtr1 A G 17: 29,901,139 (GRCm39) M249V probably benign Het
Cmya5 A G 13: 93,231,674 (GRCm39) L1138P probably damaging Het
Crim1 A C 17: 78,610,517 (GRCm39) D324A probably damaging Het
Dmap1 T A 4: 117,532,732 (GRCm39) probably null Het
Dnah17 T C 11: 118,010,397 (GRCm39) Y307C probably benign Het
Dnah5 T A 15: 28,270,566 (GRCm39) L956H probably damaging Het
Enpp3 C T 10: 24,663,750 (GRCm39) S537N probably damaging Het
Eya3 T A 4: 132,439,173 (GRCm39) L323Q probably damaging Het
Fads3 A T 19: 10,031,631 (GRCm39) H226L probably damaging Het
Flrt3 T A 2: 140,502,365 (GRCm39) D421V possibly damaging Het
Frmd4a T C 2: 4,607,060 (GRCm39) V370A possibly damaging Het
Gapvd1 T C 2: 34,580,471 (GRCm39) probably null Het
Gm2178 T C 14: 26,235,995 (GRCm39) probably benign Het
Gm5592 A G 7: 40,937,888 (GRCm39) N390S probably benign Het
Hoxa10 T A 6: 52,211,800 (GRCm39) R39* probably null Het
Kcnj1 A G 9: 32,308,478 (GRCm39) T281A probably damaging Het
Myo10 T C 15: 25,805,745 (GRCm39) Y1709H probably benign Het
Nacad T C 11: 6,549,810 (GRCm39) D1127G probably benign Het
Naip1 T A 13: 100,581,245 (GRCm39) M1L probably damaging Het
Or10ak9 A T 4: 118,726,341 (GRCm39) Y121F probably benign Het
Or6c215 G A 10: 129,637,689 (GRCm39) A235V probably damaging Het
Or6c215 C A 10: 129,637,690 (GRCm39) A235S probably damaging Het
Pcdhb12 G A 18: 37,568,695 (GRCm39) probably benign Het
Pde1b T C 15: 103,429,909 (GRCm39) V134A probably damaging Het
Plxnb2 A T 15: 89,042,203 (GRCm39) D1600E probably benign Het
Prss54 T A 8: 96,292,086 (GRCm39) probably null Het
Ryr3 A T 2: 112,465,741 (GRCm39) I4757N probably damaging Het
Slc1a6 T C 10: 78,624,822 (GRCm39) Y76H possibly damaging Het
Slco3a1 C T 7: 73,968,254 (GRCm39) D489N probably benign Het
Sox15 G T 11: 69,546,716 (GRCm39) G173V possibly damaging Het
Stard3 T C 11: 98,263,088 (GRCm39) S48P probably damaging Het
Stk32c G A 7: 138,702,839 (GRCm39) Q67* probably null Het
Svil T A 18: 5,116,016 (GRCm39) W2101R probably damaging Het
Taar7e T A 10: 23,914,427 (GRCm39) Y306N probably damaging Het
Tarbp1 T A 8: 127,154,280 (GRCm39) M1485L probably benign Het
Togaram1 A G 12: 65,014,261 (GRCm39) D504G probably damaging Het
Trrap T C 5: 144,739,771 (GRCm39) L1091S possibly damaging Het
Unc80 A G 1: 66,714,226 (GRCm39) E2856G possibly damaging Het
Usp47 C T 7: 111,687,139 (GRCm39) T699M probably damaging Het
Other mutations in Cacna1a
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00507:Cacna1a APN 8 85,297,837 (GRCm39) nonsense probably null
IGL00513:Cacna1a APN 8 85,279,685 (GRCm39) missense probably damaging 1.00
IGL00569:Cacna1a APN 8 85,189,343 (GRCm39) missense probably damaging 1.00
IGL00981:Cacna1a APN 8 85,275,182 (GRCm39) missense probably damaging 1.00
IGL01122:Cacna1a APN 8 85,341,422 (GRCm39) critical splice donor site probably null
IGL01309:Cacna1a APN 8 85,249,657 (GRCm39) missense probably damaging 1.00
IGL01380:Cacna1a APN 8 85,285,746 (GRCm39) missense probably damaging 1.00
IGL01638:Cacna1a APN 8 85,298,456 (GRCm39) missense probably damaging 0.98
IGL01682:Cacna1a APN 8 85,263,067 (GRCm39) missense possibly damaging 0.71
IGL02751:Cacna1a APN 8 85,296,581 (GRCm39) missense probably damaging 1.00
IGL02904:Cacna1a APN 8 85,306,149 (GRCm39) missense probably damaging 1.00
IGL03122:Cacna1a APN 8 85,189,305 (GRCm39) splice site probably benign
totter UTSW 8 85,315,382 (GRCm39) missense probably damaging 0.99
totter2 UTSW 8 85,315,382 (GRCm39) missense probably damaging 0.99
FR4340:Cacna1a UTSW 8 85,365,352 (GRCm39) small insertion probably benign
FR4449:Cacna1a UTSW 8 85,365,352 (GRCm39) small insertion probably benign
FR4449:Cacna1a UTSW 8 85,365,349 (GRCm39) small insertion probably benign
FR4449:Cacna1a UTSW 8 85,365,343 (GRCm39) small insertion probably benign
FR4548:Cacna1a UTSW 8 85,365,346 (GRCm39) small insertion probably benign
FR4737:Cacna1a UTSW 8 85,365,355 (GRCm39) small insertion probably benign
FR4737:Cacna1a UTSW 8 85,365,349 (GRCm39) small insertion probably benign
FR4976:Cacna1a UTSW 8 85,365,355 (GRCm39) small insertion probably benign
FR4976:Cacna1a UTSW 8 85,365,346 (GRCm39) small insertion probably benign
IGL03134:Cacna1a UTSW 8 85,285,716 (GRCm39) missense probably damaging 1.00
R0055:Cacna1a UTSW 8 85,306,687 (GRCm39) splice site probably benign
R0118:Cacna1a UTSW 8 85,262,712 (GRCm39) missense probably damaging 1.00
R0284:Cacna1a UTSW 8 85,338,914 (GRCm39) missense probably damaging 1.00
R0581:Cacna1a UTSW 8 85,328,565 (GRCm39) missense possibly damaging 0.83
R0607:Cacna1a UTSW 8 85,356,460 (GRCm39) missense probably damaging 1.00
R1168:Cacna1a UTSW 8 85,306,130 (GRCm39) missense probably damaging 1.00
R1183:Cacna1a UTSW 8 85,306,846 (GRCm39) missense probably damaging 1.00
R1470:Cacna1a UTSW 8 85,241,579 (GRCm39) splice site probably benign
R1503:Cacna1a UTSW 8 85,328,575 (GRCm39) missense probably benign 0.23
R1522:Cacna1a UTSW 8 85,360,062 (GRCm39) missense probably benign 0.00
R1835:Cacna1a UTSW 8 85,307,986 (GRCm39) splice site probably null
R1862:Cacna1a UTSW 8 85,142,559 (GRCm39) missense possibly damaging 0.80
R2148:Cacna1a UTSW 8 85,356,304 (GRCm39) missense possibly damaging 0.71
R2237:Cacna1a UTSW 8 85,360,394 (GRCm39) critical splice donor site probably null
R2567:Cacna1a UTSW 8 85,276,354 (GRCm39) missense probably damaging 1.00
R2999:Cacna1a UTSW 8 85,294,371 (GRCm39) missense probably damaging 1.00
R3025:Cacna1a UTSW 8 85,306,854 (GRCm39) critical splice donor site probably null
R3610:Cacna1a UTSW 8 85,285,694 (GRCm39) missense probably damaging 1.00
R3702:Cacna1a UTSW 8 85,344,475 (GRCm39) missense probably damaging 0.98
R3763:Cacna1a UTSW 8 85,310,271 (GRCm39) missense possibly damaging 0.85
R4025:Cacna1a UTSW 8 85,307,962 (GRCm39) missense probably damaging 1.00
R4026:Cacna1a UTSW 8 85,307,962 (GRCm39) missense probably damaging 1.00
R4106:Cacna1a UTSW 8 85,310,324 (GRCm39) missense possibly damaging 0.85
R4296:Cacna1a UTSW 8 85,285,922 (GRCm39) missense probably damaging 1.00
R4664:Cacna1a UTSW 8 85,328,396 (GRCm39) nonsense probably null
R4713:Cacna1a UTSW 8 85,276,143 (GRCm39) missense probably damaging 1.00
R5223:Cacna1a UTSW 8 85,313,824 (GRCm39) missense possibly damaging 0.94
R5408:Cacna1a UTSW 8 85,276,336 (GRCm39) missense probably damaging 1.00
R5644:Cacna1a UTSW 8 85,189,406 (GRCm39) missense probably damaging 1.00
R5734:Cacna1a UTSW 8 85,310,360 (GRCm39) missense probably damaging 0.96
R5786:Cacna1a UTSW 8 85,142,350 (GRCm39) unclassified probably benign
R5833:Cacna1a UTSW 8 85,245,326 (GRCm39) missense probably damaging 1.00
R5886:Cacna1a UTSW 8 85,249,651 (GRCm39) missense probably damaging 0.99
R6049:Cacna1a UTSW 8 85,365,475 (GRCm39) missense probably damaging 0.96
R6054:Cacna1a UTSW 8 85,283,414 (GRCm39) missense probably damaging 0.99
R6149:Cacna1a UTSW 8 85,296,581 (GRCm39) missense probably damaging 1.00
R6195:Cacna1a UTSW 8 85,315,382 (GRCm39) missense probably damaging 0.99
R6233:Cacna1a UTSW 8 85,315,382 (GRCm39) missense probably damaging 0.99
R6607:Cacna1a UTSW 8 85,306,121 (GRCm39) missense probably damaging 1.00
R6753:Cacna1a UTSW 8 85,306,834 (GRCm39) missense probably damaging 1.00
R6798:Cacna1a UTSW 8 85,338,231 (GRCm39) missense probably damaging 1.00
R6831:Cacna1a UTSW 8 85,297,860 (GRCm39) missense probably damaging 1.00
R6980:Cacna1a UTSW 8 85,338,914 (GRCm39) missense possibly damaging 0.85
R7051:Cacna1a UTSW 8 85,356,544 (GRCm39) missense possibly damaging 0.85
R7270:Cacna1a UTSW 8 85,297,866 (GRCm39) missense probably damaging 1.00
R7409:Cacna1a UTSW 8 85,260,031 (GRCm39) missense probably damaging 1.00
R7491:Cacna1a UTSW 8 85,285,922 (GRCm39) missense possibly damaging 0.92
R7511:Cacna1a UTSW 8 85,294,311 (GRCm39) missense possibly damaging 0.75
R7745:Cacna1a UTSW 8 85,286,023 (GRCm39) missense probably benign 0.01
R7872:Cacna1a UTSW 8 85,310,283 (GRCm39) missense probably damaging 1.00
R7899:Cacna1a UTSW 8 85,320,802 (GRCm39) missense possibly damaging 0.72
R7986:Cacna1a UTSW 8 85,365,408 (GRCm39) missense probably benign 0.02
R8126:Cacna1a UTSW 8 85,359,881 (GRCm39) missense probably benign 0.02
R8266:Cacna1a UTSW 8 85,285,848 (GRCm39) missense probably damaging 1.00
R8458:Cacna1a UTSW 8 85,276,087 (GRCm39) missense probably damaging 1.00
R8504:Cacna1a UTSW 8 85,365,370 (GRCm39) missense probably benign
R8530:Cacna1a UTSW 8 85,339,043 (GRCm39) critical splice donor site probably null
R8750:Cacna1a UTSW 8 85,285,784 (GRCm39) missense probably damaging 0.99
R8817:Cacna1a UTSW 8 85,365,426 (GRCm39) missense probably benign 0.44
R8856:Cacna1a UTSW 8 85,286,070 (GRCm39) missense probably benign 0.30
R8893:Cacna1a UTSW 8 85,313,764 (GRCm39) missense probably benign 0.00
R9083:Cacna1a UTSW 8 85,344,511 (GRCm39) missense probably benign 0.30
R9087:Cacna1a UTSW 8 85,365,432 (GRCm39) missense probably benign 0.44
R9118:Cacna1a UTSW 8 85,262,715 (GRCm39) missense probably damaging 1.00
R9133:Cacna1a UTSW 8 85,276,152 (GRCm39) missense probably damaging 1.00
R9175:Cacna1a UTSW 8 85,296,644 (GRCm39) missense probably damaging 0.99
R9233:Cacna1a UTSW 8 85,271,283 (GRCm39) missense probably damaging 1.00
R9310:Cacna1a UTSW 8 85,263,046 (GRCm39) missense probably damaging 1.00
R9331:Cacna1a UTSW 8 85,142,446 (GRCm39) missense probably damaging 1.00
R9334:Cacna1a UTSW 8 85,296,594 (GRCm39) missense probably damaging 1.00
R9531:Cacna1a UTSW 8 85,320,801 (GRCm39) missense probably benign 0.02
R9532:Cacna1a UTSW 8 85,338,246 (GRCm39) missense probably damaging 1.00
R9590:Cacna1a UTSW 8 85,328,610 (GRCm39) nonsense probably null
R9710:Cacna1a UTSW 8 85,320,808 (GRCm39) missense possibly damaging 0.74
RF029:Cacna1a UTSW 8 85,365,353 (GRCm39) small insertion probably benign
X0022:Cacna1a UTSW 8 85,360,328 (GRCm39) missense possibly damaging 0.53
Z1176:Cacna1a UTSW 8 85,142,305 (GRCm39) missense unknown
Z1177:Cacna1a UTSW 8 85,306,120 (GRCm39) missense probably damaging 1.00
Z1188:Cacna1a UTSW 8 85,241,683 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- CGTCTGTAAATGCATCCAAGC -3'
(R):5'- CTGGAGGCTAAGAGTTTGCTAG -3'

Sequencing Primer
(F):5'- TGTAAATGCATCCAAGCCTTTACCG -3'
(R):5'- AGGCTAAGAGTTTGCTAGTTTAATGC -3'
Posted On 2017-08-16