Incidental Mutation 'R1024:Cacna2d2'
ID 98759
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 039126-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.859) question?
Stock # R1024 (G1)
Quality Score 131
Status Not validated
Chromosome 9
Chromosomal Location 107276948-107406545 bp(+) (GRCm39)
Type of Mutation critical splice donor site (2 bp from exon)
DNA Base Change (assembly) T to C at 107404249 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000130451 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000010210] [ENSMUST00000085092] [ENSMUST00000164988] [ENSMUST00000166799] [ENSMUST00000168532] [ENSMUST00000170737]
AlphaFold Q6PHS9
Predicted Effect probably benign
Transcript: ENSMUST00000010210
SMART Domains Protein: ENSMUSP00000010210
Gene: ENSMUSG00000010066

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
SMART Domains Protein: ENSMUSP00000082173
Gene: ENSMUSG00000010066

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 null
Transcript: ENSMUST00000164988
SMART Domains Protein: ENSMUSP00000130451
Gene: ENSMUSG00000010066

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
SMART Domains Protein: ENSMUSP00000126029
Gene: ENSMUSG00000010066

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
SMART Domains Protein: ENSMUSP00000132512
Gene: ENSMUSG00000010066

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
SMART Domains Protein: ENSMUSP00000125943
Gene: ENSMUSG00000010066

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: 99.5%
  • 3x: 98.4%
  • 10x: 95.6%
  • 20x: 90.2%
Validation Efficiency 90% (36/40)
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: 66 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Akap13 T C 7: 75,327,157 (GRCm39) S719P probably damaging Het
Atxn2l A T 7: 126,096,466 (GRCm39) N425K probably benign Het
B3galt4 G A 17: 34,169,813 (GRCm39) R142C probably damaging Het
Ccar2 A G 14: 70,377,964 (GRCm39) S674P probably damaging Het
Ccm2 T A 11: 6,520,119 (GRCm39) Y56* probably null Het
Cdc14b A T 13: 64,363,490 (GRCm39) V257E probably damaging Het
Cdca8 A C 4: 124,815,798 (GRCm39) S171R probably benign Het
Cep192 C T 18: 67,971,125 (GRCm39) T1042I probably benign Het
Cfap100 T A 6: 90,389,986 (GRCm39) T101S possibly damaging Het
Cfap46 T A 7: 139,222,513 (GRCm39) M1155L probably benign Het
Cyp3a13 T A 5: 137,892,626 (GRCm39) I473F possibly damaging Het
Dclk3 A G 9: 111,298,138 (GRCm39) I561V possibly damaging Het
Dock6 A T 9: 21,744,908 (GRCm39) L556H probably damaging Het
Dqx1 G A 6: 83,038,070 (GRCm39) C486Y probably damaging Het
Drd1 T A 13: 54,207,333 (GRCm39) M294L probably benign Het
Dsel A G 1: 111,788,403 (GRCm39) S711P probably damaging Het
Fcho2 A T 13: 98,869,167 (GRCm39) I568N probably damaging Het
Folr1 A G 7: 101,507,810 (GRCm39) M210T probably damaging Het
Gatc T A 5: 115,478,904 (GRCm39) probably null Het
Gja8 A T 3: 96,826,740 (GRCm39) F307L probably benign Het
H1f7 G A 15: 98,154,636 (GRCm39) T171I unknown Het
Hnrnpd C A 5: 100,114,016 (GRCm39) *87L probably null Het
Hpd C T 5: 123,312,532 (GRCm39) R279H possibly damaging Het
Igfals G A 17: 25,099,457 (GRCm39) V183M probably damaging Het
Izumo1 A G 7: 45,276,598 (GRCm39) Y387C probably benign Het
Kdm5a A G 6: 120,375,999 (GRCm39) N585S probably null Het
Marchf2 C A 17: 33,928,762 (GRCm39) G45C probably damaging Het
Myo15a A T 11: 60,370,442 (GRCm39) R1067S probably benign Het
Naip2 T C 13: 100,298,362 (GRCm39) E558G probably benign Het
Naip2 C T 13: 100,298,368 (GRCm39) G556D probably benign Het
Nell1 A G 7: 49,770,411 (GRCm39) S157G probably damaging Het
Nf1 A T 11: 79,437,859 (GRCm39) E2072D probably damaging Het
Nipal1 CGGG CGG 5: 72,825,334 (GRCm39) probably null Het
Nop2 T A 6: 125,114,149 (GRCm39) V205E probably benign Het
Nphs1 G T 7: 30,173,702 (GRCm39) S939I probably damaging Het
Nudt8 T A 19: 4,051,925 (GRCm39) W179R probably damaging Het
Nutm1 A T 2: 112,080,274 (GRCm39) I547N probably benign Het
Oog2 A C 4: 143,922,856 (GRCm39) T374P probably damaging Het
Or4k5 A T 14: 50,385,384 (GRCm39) F316I probably benign Het
Or8b54 C A 9: 38,686,631 (GRCm39) L27I probably damaging Het
Otud4 T A 8: 80,390,722 (GRCm39) M413K probably benign Het
Pear1 A G 3: 87,667,606 (GRCm39) probably benign Het
Pla2g3 G A 11: 3,438,551 (GRCm39) C67Y probably damaging Het
Plxdc2 A G 2: 16,716,917 (GRCm39) T334A probably benign Het
Ppl G A 16: 4,917,864 (GRCm39) R543W probably damaging Het
Prl5a1 G A 13: 28,333,880 (GRCm39) V128I probably damaging Het
Pth1r A T 9: 110,571,295 (GRCm39) L25Q probably damaging Het
Pth1r T C 9: 110,558,689 (GRCm39) D96G probably benign Het
Rfpl4 G T 7: 5,113,517 (GRCm39) D215E probably damaging Het
Rnf146 T A 10: 29,223,092 (GRCm39) R265* probably null Het
Rpe65 T C 3: 159,312,122 (GRCm39) I207T probably benign Het
Rptn A G 3: 93,305,532 (GRCm39) E955G possibly damaging Het
Rwdd2b A T 16: 87,233,738 (GRCm39) C121S probably damaging Het
Scn10a A G 9: 119,438,340 (GRCm39) I1843T probably damaging Het
Sirt5 A G 13: 43,524,245 (GRCm39) I6V probably benign Het
Slc25a36 A G 9: 96,961,254 (GRCm39) Y261H probably damaging Het
Slc5a3 G A 16: 91,874,383 (GRCm39) A147T probably damaging Het
Stk39 T C 2: 68,240,390 (GRCm39) S114G probably damaging Het
Stxbp1 T C 2: 32,704,979 (GRCm39) probably null Het
Syt3 G T 7: 44,040,106 (GRCm39) G113V probably damaging Het
Tatdn2 A G 6: 113,686,506 (GRCm39) T644A probably damaging Het
Trim9 T A 12: 70,298,791 (GRCm39) probably null Het
Tut1 A G 19: 8,936,719 (GRCm39) N181S probably benign Het
Vill T C 9: 118,895,892 (GRCm39) S151P probably damaging Het
Vmn2r90 A T 17: 17,948,400 (GRCm39) I549F probably damaging Het
Wdfy4 T C 14: 32,801,923 (GRCm39) T1912A possibly 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
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
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'- GGCTCGGTGAACGCATCCTATAATG -3'
(R):5'- ATGTGCGGACCTCTTCGGTATCTC -3'

Sequencing Primer
(F):5'- CATCATTGACTGCGGAAACTG -3'
(R):5'- GTATCTCGGTCTCTGCACCAG -3'
Posted On 2014-01-09