Incidental Mutation 'R9584:Cacna2d2'
ID 722708
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
Accession Numbers
Essential gene? Probably essential (E-score: 0.859) question?
Stock # R9584 (G1)
Quality Score 225.009
Status Not validated
Chromosome 9
Chromosomal Location 107276948-107406545 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 107277404 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Proline at position 46 (L46P)
Ref Sequence ENSEMBL: ENSMUSP00000010210 (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: L46P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000010210
Gene: ENSMUSG00000010066
AA Change: L46P

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 possibly damaging
Transcript: ENSMUST00000085092
AA Change: L46P

PolyPhen 2 Score 0.956 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000082173
Gene: ENSMUSG00000010066
AA Change: L46P

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: L46P

PolyPhen 2 Score 0.956 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000130451
Gene: ENSMUSG00000010066
AA Change: L46P

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: L46P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000126029
Gene: ENSMUSG00000010066
AA Change: L46P

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: L46P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000132512
Gene: ENSMUSG00000010066
AA Change: L46P

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 probably damaging
Transcript: ENSMUST00000170737
AA Change: L46P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000125943
Gene: ENSMUSG00000010066
AA Change: L46P

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.8%
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: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adamts16 T G 13: 70,949,136 (GRCm39) D175A probably damaging Het
Ankhd1 A T 18: 36,798,504 (GRCm39) N635Y probably benign Het
Asxl2 T C 12: 3,550,667 (GRCm39) V803A possibly damaging Het
Brsk1 T A 7: 4,709,662 (GRCm39) S430T possibly damaging Het
Btbd8 A T 5: 107,658,347 (GRCm39) H1639L probably benign Het
Casz1 A G 4: 148,985,704 (GRCm39) probably benign Het
Catsper2 A T 2: 121,230,301 (GRCm39) N344K probably damaging Het
Ccdc80 A G 16: 44,915,675 (GRCm39) S144G probably damaging Het
Cdh10 A T 15: 18,992,095 (GRCm39) L451F probably benign Het
Chil6 A G 3: 106,301,672 (GRCm39) F143L probably damaging Het
Dock7 G A 4: 98,861,481 (GRCm39) R1379* probably null Het
Dop1a C A 9: 86,385,151 (GRCm39) L366I possibly damaging Het
Foxg1 G A 12: 49,432,406 (GRCm39) V380M possibly damaging Het
Foxo3 C T 10: 42,073,021 (GRCm39) V499M probably damaging Het
Gm10549 C T 18: 33,597,375 (GRCm39) P54S unknown Het
Grip1 G A 10: 119,874,569 (GRCm39) E778K possibly damaging Het
Hipk3 A G 2: 104,301,910 (GRCm39) V94A probably benign Het
Impg1 T C 9: 80,322,849 (GRCm39) H52R probably benign Het
Kcnv2 T C 19: 27,300,265 (GRCm39) S39P probably damaging Het
Knop1 G A 7: 118,447,709 (GRCm39) S417L unknown Het
Muc1 C T 3: 89,138,373 (GRCm39) T405I probably benign Het
Nlrp2 C A 7: 5,322,215 (GRCm39) D811Y probably damaging Het
Nvl A G 1: 180,958,431 (GRCm39) L206S probably benign Het
Or5ac19 A G 16: 59,089,580 (GRCm39) L150S probably benign Het
Or8g17 G A 9: 38,930,462 (GRCm39) A125V probably damaging Het
Orai3 G T 7: 127,373,177 (GRCm39) R226L probably benign Het
Pacs1 T C 19: 5,322,622 (GRCm39) M99V probably benign Het
Pag1 A G 3: 9,761,214 (GRCm39) S298P probably damaging Het
Pde4c T C 8: 71,200,728 (GRCm39) V419A probably benign Het
Pitpna C A 11: 75,510,368 (GRCm39) N208K probably benign Het
Pnpo C A 11: 96,831,705 (GRCm39) E114* probably null Het
Pou5f2 A G 13: 78,173,592 (GRCm39) E178G possibly damaging Het
Psph G A 5: 129,847,752 (GRCm39) R65C probably damaging Het
Sgsh T C 11: 119,241,789 (GRCm39) S106G possibly damaging Het
Synrg A G 11: 83,900,200 (GRCm39) K724R probably damaging Het
Tet1 A T 10: 62,655,306 (GRCm39) F1538L probably damaging Het
Thada G A 17: 84,733,605 (GRCm39) T1014I probably benign Het
Topbp1 T C 9: 103,219,242 (GRCm39) W1165R probably damaging Het
Trrap G A 5: 144,777,330 (GRCm39) V3043M probably damaging Het
Tshz1 G A 18: 84,033,089 (GRCm39) H440Y probably damaging Het
Vwa8 A G 14: 79,394,549 (GRCm39) D1550G 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
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
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'- CTCAAAGCGCTTGGAGCCAG -3'
(R):5'- TTGCAGCATGCCATGGGAAC -3'

Sequencing Primer
(F):5'- TGGAGAAGAGGCCGGCTTTC -3'
(R):5'- GGAACCAGAGCCCCCGC -3'
Posted On 2022-08-09