Incidental Mutation 'R1774:Cacna2d2'
ID 196938
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 039805-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.859) question?
Stock # R1774 (G1)
Quality Score 225
Status Not validated
Chromosome 9
Chromosomal Location 107276948-107406545 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 107403350 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Phenylalanine at position 944 (Y944F)
Ref Sequence ENSEMBL: ENSMUSP00000126029 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000010210] [ENSMUST00000085092] [ENSMUST00000164988] [ENSMUST00000166799] [ENSMUST00000168532] [ENSMUST00000170737]
AlphaFold Q6PHS9
Predicted Effect probably benign
Transcript: ENSMUST00000010210
AA Change: Y937F

PolyPhen 2 Score 0.158 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000010210
Gene: ENSMUSG00000010066
AA Change: Y937F

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 benign
Transcript: ENSMUST00000085092
AA Change: Y943F

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)
SMART Domains Protein: ENSMUSP00000082173
Gene: ENSMUSG00000010066
AA Change: Y943F

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 probably benign
Transcript: ENSMUST00000164988
AA Change: Y943F

PolyPhen 2 Score 0.117 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000130451
Gene: ENSMUSG00000010066
AA Change: Y943F

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 benign
Transcript: ENSMUST00000166799
AA Change: Y944F

PolyPhen 2 Score 0.195 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000126029
Gene: ENSMUSG00000010066
AA Change: Y944F

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 benign
Transcript: ENSMUST00000168532
AA Change: Y943F

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)
SMART Domains Protein: ENSMUSP00000132512
Gene: ENSMUSG00000010066
AA Change: Y943F

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: ENSMUST00000168959
Predicted Effect probably benign
Transcript: ENSMUST00000170737
AA Change: Y937F

PolyPhen 2 Score 0.095 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000125943
Gene: ENSMUSG00000010066
AA Change: Y937F

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: ENSMUST00000194842
Coding Region Coverage
  • 1x: 97.4%
  • 3x: 96.8%
  • 10x: 95.2%
  • 20x: 92.0%
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: 85 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700018F24Rik T C 5: 144,982,351 (GRCm39) V312A probably damaging Het
2810408A11Rik A G 11: 69,791,453 (GRCm39) V42A probably damaging Het
Akap8l C T 17: 32,551,457 (GRCm39) R511H probably damaging Het
Angpt1 T A 15: 42,387,012 (GRCm39) Q114L probably damaging Het
Apc2 T C 10: 80,144,964 (GRCm39) I625T probably damaging Het
Atg2a T C 19: 6,300,628 (GRCm39) V735A probably benign Het
Birc6 T A 17: 74,947,008 (GRCm39) I2909N probably damaging Het
C7 C G 15: 5,041,557 (GRCm39) D450H probably damaging Het
Cachd1 C T 4: 100,821,632 (GRCm39) T403I probably damaging Het
Cachd1 T A 4: 100,824,240 (GRCm39) F560L probably benign Het
Cdkal1 C T 13: 30,034,031 (GRCm39) D21N probably damaging Het
Col18a1 T C 10: 76,895,815 (GRCm39) R901G probably damaging Het
Col27a1 C T 4: 63,143,950 (GRCm39) P546L probably damaging Het
Cps1 C T 1: 67,210,041 (GRCm39) R624W possibly damaging Het
Cyp11a1 A T 9: 57,925,643 (GRCm39) I93F probably benign Het
Cyp2c40 G C 19: 39,775,250 (GRCm39) T334R probably damaging Het
Cyp4f37 A G 17: 32,848,864 (GRCm39) D244G possibly damaging Het
D630003M21Rik A T 2: 158,062,390 (GRCm39) D43E probably damaging Het
Ep400 C A 5: 110,833,357 (GRCm39) C1955F unknown Het
Ethe1 G A 7: 24,293,371 (GRCm39) V6I probably benign Het
F5 C A 1: 164,020,104 (GRCm39) Q860K probably benign Het
Fasn T C 11: 120,707,997 (GRCm39) Y685C probably damaging Het
Gga2 T G 7: 121,611,444 (GRCm39) D38A probably damaging Het
Gm43302 T A 5: 105,423,660 (GRCm39) I438F probably benign Het
Grm1 T A 10: 10,955,610 (GRCm39) T225S possibly damaging Het
Hic2 G T 16: 17,076,511 (GRCm39) V447L probably damaging Het
Hsf2 G A 10: 57,388,242 (GRCm39) C462Y probably damaging Het
Ice1 T C 13: 70,752,672 (GRCm39) D1138G probably damaging Het
Il6 A G 5: 30,224,433 (GRCm39) T158A probably benign Het
Inpp5d T A 1: 87,595,611 (GRCm39) V120E probably benign Het
Iqca1 T C 1: 90,008,625 (GRCm39) N456S probably benign Het
Itgal T A 7: 126,908,794 (GRCm39) probably null Het
Lrrc66 G C 5: 73,768,198 (GRCm39) Q248E probably benign Het
Lrrc7 T A 3: 157,865,929 (GRCm39) M1271L possibly damaging Het
Lrrc74a T C 12: 86,795,827 (GRCm39) S267P probably damaging Het
Map2 T C 1: 66,453,233 (GRCm39) S550P probably damaging Het
Mapk8ip3 A T 17: 25,143,119 (GRCm39) probably null Het
Mdm4 A C 1: 132,924,384 (GRCm39) S246A probably damaging Het
Med23 A G 10: 24,779,584 (GRCm39) E887G probably damaging Het
Mta1 C T 12: 113,091,659 (GRCm39) A254V probably damaging Het
Myh2 A G 11: 67,064,300 (GRCm39) Y85C possibly damaging Het
Myo1g A G 11: 6,465,988 (GRCm39) Y366H probably damaging Het
Nalcn G A 14: 123,515,678 (GRCm39) P1708S probably benign Het
Nlrp9c A T 7: 26,093,543 (GRCm39) S41T probably benign Het
Nptx2 T A 5: 144,490,248 (GRCm39) S226T possibly damaging Het
Nup85 T A 11: 115,473,771 (GRCm39) S562T probably benign Het
Nxpe5 T C 5: 138,237,797 (GRCm39) V107A probably benign Het
Obi1 A G 14: 104,717,098 (GRCm39) V425A possibly damaging Het
Oga T C 19: 45,765,423 (GRCm39) E128G probably benign Het
Or10ac1 A T 6: 42,515,453 (GRCm39) F168I probably damaging Het
Or10al7 A G 17: 38,366,328 (GRCm39) V43A probably benign Het
Or13c3 T A 4: 52,855,674 (GRCm39) I280F probably benign Het
Or6p1 A G 1: 174,258,905 (GRCm39) T304A probably benign Het
Pcdhb12 C T 18: 37,569,495 (GRCm39) P214S possibly damaging Het
Pcdhb5 T A 18: 37,455,725 (GRCm39) F702I probably damaging Het
Pcnx1 T C 12: 82,022,094 (GRCm39) F1475S probably damaging Het
Pde5a C A 3: 122,523,013 (GRCm39) T40N probably benign Het
Pnpla2 T A 7: 141,039,481 (GRCm39) V398E probably damaging Het
Pramel19 G A 4: 101,797,655 (GRCm39) V18M probably benign Het
Pwwp4a G T X: 72,171,261 (GRCm39) G218C probably damaging Het
Rab20 T C 8: 11,504,223 (GRCm39) K159R probably benign Het
Rfwd3 C T 8: 112,014,874 (GRCm39) R326Q probably damaging Het
Rgs12 T A 5: 35,123,747 (GRCm39) V510D probably benign Het
Slamf6 T C 1: 171,770,154 (GRCm39) probably benign Het
Slc27a5 A T 7: 12,731,534 (GRCm39) C23* probably null Het
Slc35e2 T C 4: 155,694,621 (GRCm39) V56A possibly damaging Het
Slx4ip T C 2: 136,909,643 (GRCm39) S143P probably damaging Het
Stat5a C T 11: 100,770,112 (GRCm39) S463F probably damaging Het
Svep1 T C 4: 58,146,562 (GRCm39) D360G possibly damaging Het
Tas2r143 A T 6: 42,377,305 (GRCm39) D45V probably damaging Het
Tdrd5 G T 1: 156,105,079 (GRCm39) R516S probably damaging Het
Thy1 A G 9: 43,958,636 (GRCm39) D126G probably benign Het
Tspear C T 10: 77,709,019 (GRCm39) T415I probably benign Het
Ttll5 C A 12: 85,980,176 (GRCm39) T920K probably benign Het
Tut4 T C 4: 108,365,152 (GRCm39) F542L probably damaging Het
Umod T C 7: 119,076,574 (GRCm39) E64G possibly damaging Het
Usf3 A G 16: 44,036,033 (GRCm39) N171S probably damaging Het
Vmn1r23 T A 6: 57,903,675 (GRCm39) R34S probably damaging Het
Wasf1 C G 10: 40,810,475 (GRCm39) P239R possibly damaging Het
Wdr95 C T 5: 149,487,857 (GRCm39) R164* probably null Het
Zan C A 5: 137,418,251 (GRCm39) C2949F unknown Het
Zbed4 T C 15: 88,665,080 (GRCm39) S383P probably benign Het
Zfand5 T A 19: 21,253,895 (GRCm39) C33S probably damaging Het
Zfp12 A G 5: 143,230,984 (GRCm39) Y437C probably damaging Het
Zfp451 A C 1: 33,852,849 (GRCm39) S22A probably benign 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
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
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 PCR Primer
(F):5'- GGTGCTGTCAAACCAGAACCATCAG -3'
(R):5'- AGAGGTCCACCAGGCCAAGTTAAG -3'

Sequencing Primer
(F):5'- ACCATCAGTGGGACCAGG -3'
(R):5'- AAATCTGCAATGGTGGGCTG -3'
Posted On 2014-05-23