Incidental Mutation 'R2567:Cacna1a'
ID 254557
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 040426-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.924) question?
Stock # R2567 (G1)
Quality Score 225
Status Not validated
Chromosome 8
Chromosomal Location 85065268-85366875 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 85276354 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Lysine at position 613 (M613K)
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: M613K

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000112436
Gene: ENSMUSG00000034656
AA Change: M613K

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: M566K

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000114055
Gene: ENSMUSG00000034656
AA Change: M566K

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: ENSMUST00000129620
Predicted Effect unknown
Transcript: ENSMUST00000215756
AA Change: M565K
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.1%
  • 20x: 94.6%
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: 67 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aadacl2fm1 A G 3: 59,836,475 (GRCm39) probably benign Het
Aebp1 A G 11: 5,820,251 (GRCm39) D409G probably benign Het
Akap10 A G 11: 61,784,175 (GRCm39) probably benign Het
Akap6 G T 12: 52,985,156 (GRCm39) S863I probably damaging Het
Ap1s3 T C 1: 79,602,921 (GRCm39) K29E possibly damaging Het
Atm T A 9: 53,368,770 (GRCm39) I2341L possibly damaging Het
Atp12a A T 14: 56,624,384 (GRCm39) D944V probably damaging Het
Baz2b A T 2: 59,744,255 (GRCm39) S1417T possibly damaging Het
Ccdc191 A C 16: 43,764,330 (GRCm39) probably null Het
Cd209d T A 8: 3,926,327 (GRCm39) N96I probably damaging Het
Cdh15 G A 8: 123,588,763 (GRCm39) R279Q probably damaging Het
Cdk4 T G 10: 126,900,145 (GRCm39) V14G probably benign Het
Chrna10 C A 7: 101,761,276 (GRCm39) M438I probably benign Het
Clec10a T C 11: 70,060,358 (GRCm39) probably null Het
Cog3 A G 14: 75,991,730 (GRCm39) V40A probably benign Het
Creb3l3 T C 10: 80,921,883 (GRCm39) H315R probably benign Het
Csmd3 CCTTTGCGCTT CCTT 15: 47,604,632 (GRCm39) probably null Het
Cubn A G 2: 13,283,167 (GRCm39) probably null Het
Cygb T C 11: 116,540,692 (GRCm39) D98G probably damaging Het
Dmbx1 T C 4: 115,777,489 (GRCm39) K120E probably damaging Het
Dnah3 T A 7: 119,551,920 (GRCm39) I2800F possibly damaging Het
Dntt G T 19: 41,029,775 (GRCm39) R245L possibly damaging Het
Dock1 T G 7: 134,747,213 (GRCm39) V1508G probably damaging Het
Enpp4 A C 17: 44,412,736 (GRCm39) I266R probably damaging Het
Fhl4 T C 10: 84,934,644 (GRCm39) I46V possibly damaging Het
Fn1 G A 1: 71,636,895 (GRCm39) Q1995* probably null Het
Foxl3 A G 5: 138,805,940 (GRCm39) S36G probably null Het
Foxo1 T A 3: 52,176,755 (GRCm39) L178H probably damaging Het
Galnt18 C T 7: 111,153,823 (GRCm39) R267H probably damaging Het
Gm1110 T C 9: 26,831,992 (GRCm39) D53G probably benign Het
Gm7104 A T 12: 88,252,242 (GRCm39) noncoding transcript Het
H2-M11 C T 17: 36,859,042 (GRCm39) T194I possibly damaging Het
Haus6 C A 4: 86,504,122 (GRCm39) E501* probably null Het
Ifna5 T C 4: 88,754,147 (GRCm39) V129A probably benign Het
Kdelr3 A G 15: 79,407,032 (GRCm39) I38V probably benign Het
Lamb1 A G 12: 31,319,054 (GRCm39) probably null Het
Larp7-ps T C 4: 92,079,560 (GRCm39) E87G probably benign Het
Mgat4c T A 10: 102,214,123 (GRCm39) F35L probably benign Het
Mmab A T 5: 114,571,378 (GRCm39) M166K probably benign Het
Mrpl2 A G 17: 46,958,427 (GRCm39) T70A probably benign Het
Naa11 C T 5: 97,539,618 (GRCm39) G180D probably benign Het
Npy6r T C 18: 44,408,888 (GRCm39) V103A possibly damaging Het
Nup188 A T 2: 30,231,794 (GRCm39) R1463W possibly damaging Het
Nusap1 T A 2: 119,474,311 (GRCm39) S336R possibly damaging Het
Or8b12c T A 9: 37,715,509 (GRCm39) F101I probably damaging Het
Pabpc4 T A 4: 123,191,744 (GRCm39) L589Q probably damaging Het
Pcdh12 T A 18: 38,415,149 (GRCm39) N659Y probably damaging Het
Perm1 T C 4: 156,301,575 (GRCm39) S40P probably damaging Het
Phldb1 T C 9: 44,637,322 (GRCm39) T114A probably damaging Het
Pirt C T 11: 66,816,985 (GRCm39) L99F probably damaging Het
Plxdc2 A G 2: 16,716,995 (GRCm39) R360G probably benign Het
Rhpn2 G A 7: 35,080,957 (GRCm39) probably null Het
Rpusd2 T A 2: 118,867,556 (GRCm39) I268N probably damaging Het
Sds G T 5: 120,619,646 (GRCm39) W185L probably damaging Het
Serpinb5 A G 1: 106,802,876 (GRCm39) K137R probably benign Het
Sh3pxd2a A G 19: 47,413,008 (GRCm39) V25A possibly damaging Het
Slc1a2 C T 2: 102,597,355 (GRCm39) T454I probably damaging Het
Slc25a40 T C 5: 8,480,459 (GRCm39) C70R probably damaging Het
Smoc1 G A 12: 81,214,364 (GRCm39) E260K probably damaging Het
Sparcl1 A T 5: 104,232,954 (GRCm39) F616I probably damaging Het
Ssc5d A T 7: 4,939,334 (GRCm39) D590V probably damaging Het
Tns2 C T 15: 102,017,369 (GRCm39) R281C probably damaging Het
Trpm2 C T 10: 77,777,008 (GRCm39) V430M probably damaging Het
Ttn T C 2: 76,574,672 (GRCm39) D25407G probably damaging Het
Vmn2r68 T C 7: 84,883,803 (GRCm39) I101V probably benign Het
Xrcc4 A T 13: 90,210,261 (GRCm39) M61K probably damaging Het
Zfp648 A G 1: 154,080,695 (GRCm39) T285A 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
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
R6117:Cacna1a UTSW 8 85,341,350 (GRCm39) missense probably damaging 1.00
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'- CCTTTGGAATCAGTGTGTTACG -3'
(R):5'- GAGTGTAGTTGTGCAGTGCA -3'

Sequencing Primer
(F):5'- AATCAGTGTGTTACGAGCTCTCAG -3'
(R):5'- CATGTCTGTGTGTCTGTACATGTAC -3'
Posted On 2014-12-04