Incidental Mutation 'R6037:Cacna2d2'
ID 479267
Institutional Source Beutler Lab
Gene Symbol Cacna2d2
Ensembl Gene ENSMUSG00000010066
Gene Name calcium channel, voltage-dependent, alpha 2/delta subunit 2
Synonyms a2d2
MMRRC Submission 043258-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.859) question?
Stock # R6037 (G1)
Quality Score 225.009
Status Not validated
Chromosome 9
Chromosomal Location 107276948-107406545 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 107390738 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Glutamic Acid at position 357 (K357E)
Ref Sequence ENSEMBL: ENSMUSP00000125943 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000010210] [ENSMUST00000085092] [ENSMUST00000164988] [ENSMUST00000166799] [ENSMUST00000168532] [ENSMUST00000170737]
AlphaFold Q6PHS9
Predicted Effect probably damaging
Transcript: ENSMUST00000010210
AA Change: K357E

PolyPhen 2 Score 0.964 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000010210
Gene: ENSMUSG00000010066
AA Change: K357E

DomainStartEndE-ValueType
low complexity region 20 36 N/A INTRINSIC
low complexity region 43 57 N/A INTRINSIC
Pfam:VWA_N 144 268 2e-48 PFAM
VWA 292 467 4.93e-22 SMART
Pfam:Cache_1 488 577 9.9e-32 PFAM
Pfam:VGCC_alpha2 583 673 1.8e-33 PFAM
low complexity region 968 977 N/A INTRINSIC
low complexity region 1114 1137 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000085092
AA Change: K357E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000082173
Gene: ENSMUSG00000010066
AA Change: K357E

DomainStartEndE-ValueType
low complexity region 20 36 N/A INTRINSIC
low complexity region 43 57 N/A INTRINSIC
Pfam:VWA_N 144 268 2e-48 PFAM
VWA 292 467 4.93e-22 SMART
Pfam:Cache_1 488 577 1e-31 PFAM
Pfam:VGCC_alpha2 583 676 5.8e-35 PFAM
low complexity region 974 983 N/A INTRINSIC
low complexity region 1120 1143 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000164988
AA Change: K357E

PolyPhen 2 Score 0.890 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000130451
Gene: ENSMUSG00000010066
AA Change: K357E

DomainStartEndE-ValueType
low complexity region 20 36 N/A INTRINSIC
low complexity region 43 57 N/A INTRINSIC
Pfam:VWA_N 144 268 6.7e-49 PFAM
VWA 292 467 4.93e-22 SMART
Pfam:Cache_1 488 577 2.4e-31 PFAM
Pfam:VGCC_alpha2 583 675 2.5e-34 PFAM
low complexity region 974 983 N/A INTRINSIC
low complexity region 1123 1146 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000166799
AA Change: K357E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000126029
Gene: ENSMUSG00000010066
AA Change: K357E

DomainStartEndE-ValueType
low complexity region 20 36 N/A INTRINSIC
low complexity region 43 57 N/A INTRINSIC
Pfam:VWA_N 144 268 8.5e-44 PFAM
VWA 292 467 4.93e-22 SMART
Pfam:Cache_1 488 576 1.3e-32 PFAM
Pfam:VGCC_alpha2 583 675 1.4e-47 PFAM
low complexity region 975 984 N/A INTRINSIC
low complexity region 1123 1146 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000168532
AA Change: K357E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000132512
Gene: ENSMUSG00000010066
AA Change: K357E

DomainStartEndE-ValueType
low complexity region 20 36 N/A INTRINSIC
low complexity region 43 57 N/A INTRINSIC
Pfam:VWA_N 144 268 2.1e-48 PFAM
VWA 292 467 4.93e-22 SMART
Pfam:Cache_1 488 577 1e-31 PFAM
Pfam:VGCC_alpha2 583 676 5.8e-35 PFAM
low complexity region 974 983 N/A INTRINSIC
low complexity region 1122 1145 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000169354
Predicted Effect probably damaging
Transcript: ENSMUST00000170737
AA Change: K357E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000125943
Gene: ENSMUSG00000010066
AA Change: K357E

DomainStartEndE-ValueType
low complexity region 20 36 N/A INTRINSIC
low complexity region 43 57 N/A INTRINSIC
Pfam:VWA_N 144 268 2e-48 PFAM
VWA 292 467 4.93e-22 SMART
Pfam:Cache_1 488 577 1e-31 PFAM
Pfam:VGCC_alpha2 583 673 1.9e-33 PFAM
low complexity region 968 977 N/A INTRINSIC
low complexity region 1116 1139 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000171809
Coding Region Coverage
  • 1x: 99.8%
  • 3x: 99.0%
  • 10x: 92.4%
  • 20x: 72.6%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Calcium channels mediate the entry of calcium ions into the cell upon membrane polarization. This gene encodes the alpha-2/delta subunit of the voltage-dependent calcium channel complex. The complex consists of the main channel-forming subunit alpha-1, and auxiliary subunits alpha-2/delta, beta, and gamma. The auxiliary subunits function in the assembly and membrane localization of the complex, and modulate calcium currents and channel activation/inactivation kinetics. The subunit encoded by this gene undergoes post-translational cleavage to yield the extracellular alpha2 peptide and a membrane-anchored delta polypeptide. This subunit is a receptor for the antiepileptic drug, gabapentin. Mutations in this gene are associated with early infantile epileptic encephalopathy. Single nucleotide polymorphisms in this gene are correlated with increased sensitivity to opioid drugs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]
PHENOTYPE: Homozygotes for different mutant alleles show variable movement abnormalities including waddling, reeling or very slow gait, ataxia, and mild spike-wave seizures. While gross CNS abnormalities and demyelination are present in some mutant lines, they are not observed in others. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 47 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930505A04Rik C T 11: 30,376,349 (GRCm39) V173M probably damaging Het
Abi2 C A 1: 60,503,738 (GRCm39) P212T probably damaging Het
Ano4 A G 10: 89,153,108 (GRCm39) F68S possibly damaging Het
Art5 C A 7: 101,747,591 (GRCm39) A63S probably benign Het
Asgr1 T A 11: 69,947,247 (GRCm39) S96R probably benign Het
Bdp1 A T 13: 100,163,957 (GRCm39) V2248D possibly damaging Het
Cacna1s C T 1: 135,998,705 (GRCm39) A200V possibly damaging Het
Cdhr18 T C 14: 13,864,282 (GRCm38) N348S probably damaging Het
Cfap52 C T 11: 67,837,126 (GRCm39) G212R probably benign Het
Dcun1d3 A G 7: 119,456,965 (GRCm39) F249S probably damaging Het
Ece2 A G 16: 20,449,112 (GRCm39) Y17C probably damaging Het
Efemp1 C T 11: 28,871,760 (GRCm39) T425I probably damaging Het
Eprs1 A G 1: 185,128,306 (GRCm39) E562G probably damaging Het
Fbn2 T C 18: 58,177,295 (GRCm39) T2001A probably benign Het
Flt4 G A 11: 49,527,867 (GRCm39) R940H probably damaging Het
Fry T A 5: 150,351,644 (GRCm39) M1716K probably benign Het
Gm10684 T A 9: 45,019,039 (GRCm39) probably benign Het
Hivep1 G A 13: 42,311,416 (GRCm39) V1219I probably damaging Het
Hyls1 G A 9: 35,472,480 (GRCm39) S312F probably benign Het
Il23r C T 6: 67,455,938 (GRCm39) V177M probably damaging Het
Klf12 T C 14: 100,137,650 (GRCm39) S299G probably benign Het
Lama5 G A 2: 179,848,806 (GRCm39) R265C probably damaging Het
Lifr A G 15: 7,216,424 (GRCm39) T800A probably damaging Het
Megf8 T C 7: 25,063,831 (GRCm39) L2729P probably damaging Het
Mki67 A C 7: 135,298,532 (GRCm39) S2167R possibly damaging Het
Mus81 T C 19: 5,534,032 (GRCm39) K400E probably damaging Het
Nomo1 T A 7: 45,712,423 (GRCm39) I656N possibly damaging Het
Oas3 T C 5: 120,907,384 (GRCm39) T418A probably benign Het
Olr1 A G 6: 129,470,504 (GRCm39) L221P probably damaging Het
Or14c44 C T 7: 86,062,478 (GRCm39) L303F probably benign Het
Or5m9 T C 2: 85,876,928 (GRCm39) M34T probably benign Het
Or8b3 T A 9: 38,314,601 (GRCm39) C144S probably benign Het
Or8g22 A G 9: 38,958,403 (GRCm39) V104A probably damaging Het
Or8k28 T A 2: 86,286,133 (GRCm39) I161L probably benign Het
Pih1d1 C T 7: 44,805,738 (GRCm39) A69V probably damaging Het
Pkdrej A C 15: 85,703,967 (GRCm39) S656R probably damaging Het
Polr3f A G 2: 144,377,943 (GRCm39) D171G probably damaging Het
Rasal1 T C 5: 120,787,566 (GRCm39) V11A possibly damaging Het
Rsf1 G GACGGCGGCT 7: 97,229,116 (GRCm39) probably benign Het
Sptbn4 T A 7: 27,063,595 (GRCm39) Y2277F probably damaging Het
St6galnac6 A G 2: 32,502,240 (GRCm39) Q7R probably damaging Het
Thrsp T G 7: 97,066,499 (GRCm39) D71A possibly damaging Het
Vmn2r1 C A 3: 63,989,150 (GRCm39) Q30K probably benign Het
Vmn2r125 C A 4: 156,703,396 (GRCm39) A258D probably benign Het
Wipf2 C T 11: 98,787,005 (GRCm39) P345S probably benign Het
Zeb2 G T 2: 44,878,652 (GRCm39) S1170* probably null Het
Zfp947 A G 17: 22,366,415 (GRCm39) Y38H probably damaging Het
Other mutations in Cacna2d2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00401:Cacna2d2 APN 9 107,392,072 (GRCm39) missense probably damaging 1.00
IGL00425:Cacna2d2 APN 9 107,404,550 (GRCm39) missense probably damaging 1.00
IGL01294:Cacna2d2 APN 9 107,391,280 (GRCm39) missense probably damaging 1.00
IGL01969:Cacna2d2 APN 9 107,386,415 (GRCm39) missense probably benign
IGL01974:Cacna2d2 APN 9 107,394,621 (GRCm39) missense probably benign 0.00
IGL02001:Cacna2d2 APN 9 107,399,315 (GRCm39) missense probably benign
IGL02125:Cacna2d2 APN 9 107,391,103 (GRCm39) nonsense probably null
IGL02143:Cacna2d2 APN 9 107,395,474 (GRCm39) splice site probably null
IGL02150:Cacna2d2 APN 9 107,404,515 (GRCm39) splice site probably benign
IGL02213:Cacna2d2 APN 9 107,391,247 (GRCm39) missense probably damaging 1.00
IGL02220:Cacna2d2 APN 9 107,392,078 (GRCm39) missense probably damaging 1.00
IGL02238:Cacna2d2 APN 9 107,390,757 (GRCm39) missense probably damaging 0.99
IGL02466:Cacna2d2 APN 9 107,342,753 (GRCm39) missense probably damaging 1.00
IGL02569:Cacna2d2 APN 9 107,391,245 (GRCm39) missense probably damaging 0.99
IGL02571:Cacna2d2 APN 9 107,402,845 (GRCm39) missense possibly damaging 0.93
IGL02825:Cacna2d2 APN 9 107,401,659 (GRCm39) missense probably damaging 1.00
IGL03000:Cacna2d2 APN 9 107,401,397 (GRCm39) splice site probably null
IGL03064:Cacna2d2 APN 9 107,386,474 (GRCm39) missense probably damaging 1.00
Blow UTSW 9 107,390,805 (GRCm39) missense probably null 0.90
dilemma UTSW 9 107,392,063 (GRCm39) missense probably damaging 1.00
hera UTSW 9 107,390,479 (GRCm39) missense probably damaging 1.00
Ionian UTSW 9 107,402,575 (GRCm39) missense probably benign 0.05
Solomonic UTSW 9 107,401,861 (GRCm39) missense possibly damaging 0.94
PIT4131001:Cacna2d2 UTSW 9 107,401,867 (GRCm39) missense probably damaging 1.00
R0233:Cacna2d2 UTSW 9 107,391,869 (GRCm39) missense probably damaging 0.96
R0233:Cacna2d2 UTSW 9 107,391,869 (GRCm39) missense probably damaging 0.96
R0387:Cacna2d2 UTSW 9 107,391,080 (GRCm39) missense probably damaging 1.00
R0410:Cacna2d2 UTSW 9 107,401,819 (GRCm39) missense probably damaging 1.00
R0538:Cacna2d2 UTSW 9 107,401,582 (GRCm39) splice site probably benign
R0545:Cacna2d2 UTSW 9 107,402,422 (GRCm39) missense probably damaging 1.00
R0729:Cacna2d2 UTSW 9 107,394,456 (GRCm39) missense probably benign 0.06
R1024:Cacna2d2 UTSW 9 107,404,249 (GRCm39) critical splice donor site probably null
R1538:Cacna2d2 UTSW 9 107,394,615 (GRCm39) missense probably damaging 1.00
R1750:Cacna2d2 UTSW 9 107,401,843 (GRCm39) missense probably damaging 1.00
R1774:Cacna2d2 UTSW 9 107,403,350 (GRCm39) missense probably benign 0.19
R1800:Cacna2d2 UTSW 9 107,404,632 (GRCm39) missense possibly damaging 0.46
R1873:Cacna2d2 UTSW 9 107,391,071 (GRCm39) missense probably damaging 0.98
R1935:Cacna2d2 UTSW 9 107,386,455 (GRCm39) missense probably damaging 1.00
R1936:Cacna2d2 UTSW 9 107,386,455 (GRCm39) missense probably damaging 1.00
R1971:Cacna2d2 UTSW 9 107,389,205 (GRCm39) missense probably damaging 0.98
R2095:Cacna2d2 UTSW 9 107,404,364 (GRCm39) missense probably benign 0.05
R2135:Cacna2d2 UTSW 9 107,403,712 (GRCm39) missense possibly damaging 0.74
R2197:Cacna2d2 UTSW 9 107,404,602 (GRCm39) missense probably damaging 0.97
R2266:Cacna2d2 UTSW 9 107,390,479 (GRCm39) missense probably damaging 1.00
R2483:Cacna2d2 UTSW 9 107,389,221 (GRCm39) missense probably damaging 1.00
R4021:Cacna2d2 UTSW 9 107,391,257 (GRCm39) missense probably damaging 1.00
R4392:Cacna2d2 UTSW 9 107,277,479 (GRCm39) missense possibly damaging 0.47
R4629:Cacna2d2 UTSW 9 107,404,521 (GRCm39) missense probably damaging 1.00
R5053:Cacna2d2 UTSW 9 107,392,063 (GRCm39) missense probably damaging 1.00
R5327:Cacna2d2 UTSW 9 107,390,805 (GRCm39) missense probably null 0.90
R5347:Cacna2d2 UTSW 9 107,391,313 (GRCm39) missense probably benign
R5719:Cacna2d2 UTSW 9 107,401,851 (GRCm39) missense probably benign 0.36
R5737:Cacna2d2 UTSW 9 107,403,946 (GRCm39) missense possibly damaging 0.70
R5739:Cacna2d2 UTSW 9 107,389,528 (GRCm39) missense probably benign 0.37
R6037:Cacna2d2 UTSW 9 107,390,738 (GRCm39) missense probably damaging 1.00
R6084:Cacna2d2 UTSW 9 107,374,720 (GRCm39) critical splice donor site probably null
R6170:Cacna2d2 UTSW 9 107,404,533 (GRCm39) missense probably damaging 1.00
R6254:Cacna2d2 UTSW 9 107,386,415 (GRCm39) missense probably benign
R6427:Cacna2d2 UTSW 9 107,392,641 (GRCm39) missense possibly damaging 0.67
R7652:Cacna2d2 UTSW 9 107,401,397 (GRCm39) splice site probably null
R7850:Cacna2d2 UTSW 9 107,402,575 (GRCm39) missense probably benign 0.05
R7936:Cacna2d2 UTSW 9 107,401,326 (GRCm39) missense probably damaging 1.00
R7978:Cacna2d2 UTSW 9 107,395,456 (GRCm39) missense probably benign 0.14
R8039:Cacna2d2 UTSW 9 107,404,632 (GRCm39) missense possibly damaging 0.92
R8165:Cacna2d2 UTSW 9 107,402,653 (GRCm39) splice site probably null
R8274:Cacna2d2 UTSW 9 107,401,861 (GRCm39) missense possibly damaging 0.94
R8286:Cacna2d2 UTSW 9 107,392,063 (GRCm39) missense probably damaging 1.00
R8354:Cacna2d2 UTSW 9 107,401,334 (GRCm39) missense possibly damaging 0.95
R8464:Cacna2d2 UTSW 9 107,389,206 (GRCm39) missense probably damaging 0.99
R8479:Cacna2d2 UTSW 9 107,403,596 (GRCm39) critical splice donor site probably null
R8765:Cacna2d2 UTSW 9 107,394,358 (GRCm39) missense probably damaging 1.00
R8848:Cacna2d2 UTSW 9 107,391,855 (GRCm39) missense possibly damaging 0.75
R9037:Cacna2d2 UTSW 9 107,386,395 (GRCm39) missense probably benign 0.08
R9225:Cacna2d2 UTSW 9 107,403,403 (GRCm39) missense probably benign 0.10
R9295:Cacna2d2 UTSW 9 107,386,419 (GRCm39) missense probably benign 0.02
R9372:Cacna2d2 UTSW 9 107,394,802 (GRCm39) missense probably benign 0.00
R9414:Cacna2d2 UTSW 9 107,392,395 (GRCm39) missense probably damaging 1.00
R9417:Cacna2d2 UTSW 9 107,392,689 (GRCm39) nonsense probably null
R9435:Cacna2d2 UTSW 9 107,396,384 (GRCm39) missense probably benign 0.01
R9584:Cacna2d2 UTSW 9 107,277,404 (GRCm39) missense probably damaging 0.97
R9642:Cacna2d2 UTSW 9 107,392,627 (GRCm39) missense possibly damaging 0.94
R9784:Cacna2d2 UTSW 9 107,404,346 (GRCm39) missense probably benign 0.00
Z1176:Cacna2d2 UTSW 9 107,403,301 (GRCm39) missense probably benign 0.14
Z1176:Cacna2d2 UTSW 9 107,394,492 (GRCm39) missense probably damaging 1.00
Predicted Primers
Posted On 2017-06-26