Mutagenetix > Incidental Mutations

Incidental Mutation 'R1440:Cacna2d1'

160919

Institutional Source

Beutler Lab

Gene Symbol

Cacna2d1

Ensembl Gene

ENSMUSG00000040118

Gene Name

calcium channel, voltage-dependent, alpha2/delta subunit 1

Synonyms

Ca(v)alpha2delta1, Cacna2, Cchl2a

MMRRC Submission

039495-MU

Accession Numbers

Is this an essential gene?

Possibly non essential (E-score: 0.339) question?

Stock #

R1440 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

15934691-16374511 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 16355495 bp

Zygosity

Heterozygous

Amino Acid Change

Lysine to Isoleucine at position 765 (K765I)

Ref Sequence

ENSEMBL: ENSMUSP00000136260 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000039370] [ENSMUST00000078272] [ENSMUST00000101581] [ENSMUST00000115281] [ENSMUST00000167946] [ENSMUST00000180204] [ENSMUST00000199704]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000039370
AA Change: K782I

PolyPhen 2 Score 0.719 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000049457
Gene: ENSMUSG00000040118
AA Change: K782I

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
Pfam:VWA_N	104	223	6.3e-42	PFAM
VWA	251	425	5.16e-25	SMART
Pfam:Cache_1	446	536	1e-31	PFAM
Pfam:VGCC_alpha2	562	655	1e-46	PFAM
low complexity region	675	686	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000078272
AA Change: K763I

PolyPhen 2 Score 0.616 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000077391
Gene: ENSMUSG00000040118
AA Change: K763I

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
Pfam:VWA_N	104	223	1.2e-45	PFAM
VWA	251	425	5.16e-25	SMART
Pfam:Cache_1	446	537	1.1e-30	PFAM
Pfam:VGCC_alpha2	543	634	3.3e-53	PFAM
low complexity region	656	667	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000101581
AA Change: K770I

PolyPhen 2 Score 0.616 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000099117
Gene: ENSMUSG00000040118
AA Change: K770I

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
Pfam:VWA_N	104	223	1.2e-45	PFAM
VWA	251	425	5.16e-25	SMART
Pfam:Cache_1	446	537	1.1e-30	PFAM
Pfam:VGCC_alpha2	543	636	1.2e-59	PFAM
low complexity region	663	674	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000115281
AA Change: K765I

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000110936
Gene: ENSMUSG00000040118
AA Change: K765I

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
Pfam:VWA_N	104	223	6.2e-46	PFAM
VWA	251	425	5.16e-25	SMART
Pfam:Cache_1	446	533	3.8e-30	PFAM
Pfam:VGCC_alpha2	538	631	6.2e-60	PFAM
low complexity region	658	669	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000167946
AA Change: K770I

PolyPhen 2 Score 0.667 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000131507
Gene: ENSMUSG00000040118
AA Change: K770I

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
Pfam:VWA_N	104	223	3.8e-46	PFAM
VWA	251	425	5.16e-25	SMART
Pfam:Cache_1	446	537	2.6e-30	PFAM
Pfam:VGCC_alpha2	543	636	5.5e-56	PFAM
low complexity region	663	674	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000180204
AA Change: K765I

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000136260
Gene: ENSMUSG00000040118
AA Change: K765I

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
Pfam:VWA_N	104	223	6.2e-46	PFAM
VWA	251	425	5.16e-25	SMART
Pfam:Cache_1	446	533	3.8e-30	PFAM
Pfam:VGCC_alpha2	538	631	6.2e-60	PFAM
low complexity region	658	669	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000199704
AA Change: K758I

PolyPhen 2 Score 0.616 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000142881
Gene: ENSMUSG00000040118
AA Change: K758I

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
Pfam:VWA_N	104	223	1.2e-45	PFAM
VWA	251	425	5.16e-25	SMART
Pfam:Cache_1	446	533	6.3e-30	PFAM
Pfam:VGCC_alpha2	538	629	3.3e-53	PFAM
low complexity region	651	662	N/A	INTRINSIC

Meta Mutation Damage Score

0.0838

Coding Region Coverage

1x: 98.8%
3x: 97.7%
10x: 94.0%
20x: 84.7%

Validation Efficiency

95% (94/99)

MGI Phenotype

FUNCTION: This gene encodes a regulatory component of the voltage-dependent calcium channel complex. The product of this gene is a proprotein that is proteolytically processed into alpha-2 and delta subunits, which are linked by a disulfide bond. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]
PHENOTYPE: Mice with a point mutation allele exhibit abnormal CNS synaptic transmission and decreased response to pregabalin. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 91 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930447C04Rik	T	G	12: 72,881,421	N512T	possibly damaging	Het
Aadacl2	A	T	3: 60,024,892	H276L	probably damaging	Het
Adam12	G	A	7: 133,931,814	T445M	probably benign	Het
Ash2l	A	T	8: 25,827,378	F290L	probably benign	Het
Asxl3	C	T	18: 22,525,224	P2097L	probably benign	Het
Atmin	A	G	8: 116,957,376	I592V	probably damaging	Het
Atxn2	T	C	5: 121,803,082		probably null	Het
BC004004	T	C	17: 29,296,691		probably null	Het
Cacna1e	T	C	1: 154,561,806	N328S	possibly damaging	Het
Cc2d1a	A	G	8: 84,133,975		probably null	Het
Ccdc28b	A	G	4: 129,620,615	V198A	probably benign	Het
Ces1b	G	T	8: 93,068,108	R288S	probably damaging	Het
Cfap100	T	G	6: 90,412,184	T198P	probably benign	Het
Clint1	T	C	11: 45,890,783	S227P	probably damaging	Het
Cntn5	C	A	9: 10,145,339	C122F	probably damaging	Het
Col3a1	A	G	1: 45,343,312		probably null	Het
Cyp4a10	A	C	4: 115,529,449	D431A	probably damaging	Het
Cyp4f16	CTATG	CTATGTATG	17: 32,550,734		probably null	Het
Dlc1	A	T	8: 36,593,463		probably benign	Het
Dlgap2	T	C	8: 14,727,060	S102P	probably benign	Het
Dnah7b	G	A	1: 46,078,593		probably benign	Het
Dock10	A	C	1: 80,549,136	S1124A	probably benign	Het
Dscam	C	T	16: 96,819,951	R519H	probably damaging	Het
Efcab3	A	T	11: 105,108,755		probably benign	Het
Evi2a	G	T	11: 79,527,270	N171K	probably damaging	Het
Fbxl15	T	C	19: 46,330,245	L286P	probably damaging	Het
Fpr1	T	A	17: 17,877,263	I155F	probably benign	Het
Gcat	C	T	15: 79,033,994	A84V	probably null	Het
Gls	A	G	1: 52,191,134	F473L	possibly damaging	Het
Gnat1	T	C	9: 107,676,965	D169G	probably damaging	Het
Grm3	A	C	5: 9,589,958	M29R	probably benign	Het
Herc1	A	T	9: 66,467,803	D3303V	probably damaging	Het
Ibsp	G	A	5: 104,310,539	G314D	unknown	Het
Lgr6	C	A	1: 134,987,472	A513S	probably damaging	Het
Lrmp	C	T	6: 145,174,511	T484M	possibly damaging	Het
Lrriq4	T	A	3: 30,650,761	C313S	probably damaging	Het
March10	G	T	11: 105,390,583	T292K	probably damaging	Het
Mcoln2	C	A	3: 146,190,382	Y6*	probably null	Het
Mup4	A	G	4: 59,958,076	I164T	probably damaging	Het
Myo1b	T	C	1: 51,778,558		probably benign	Het
Ncam1	A	G	9: 49,544,800	I506T	probably damaging	Het
Notch1	A	T	2: 26,480,964		probably benign	Het
Nr4a3	A	T	4: 48,051,777	Q177L	probably benign	Het
Nsun4	A	G	4: 116,052,950	S138P	possibly damaging	Het
Olfr11	G	T	13: 21,639,390	N44K	probably benign	Het
Olfr403	A	G	11: 74,195,679	M59V	probably damaging	Het
Olfr716	A	T	7: 107,148,198	N294I	probably damaging	Het
Olfr729	T	C	14: 50,148,358	N172S	probably damaging	Het
Pagr1a	A	T	7: 127,016,297		probably benign	Het
Pcdhb2	A	T	18: 37,296,290	I82L	probably benign	Het
Pds5b	A	T	5: 150,754,417	N500I	probably damaging	Het
Pik3r6	A	T	11: 68,531,445	E223D	possibly damaging	Het
Pkhd1l1	A	T	15: 44,540,988		probably benign	Het
Prex1	T	C	2: 166,580,463	D1204G	probably damaging	Het
Prickle1	C	T	15: 93,505,074	E244K	possibly damaging	Het
Ptprd	A	T	4: 76,084,552	V211E	probably damaging	Het
Rad51d	G	A	11: 82,890,353	R23*	probably null	Het
Rapgef6	G	A	11: 54,626,708	G262R	probably damaging	Het
Reln	A	G	5: 22,128,602		probably benign	Het
Rev1	T	C	1: 38,088,205	T325A	probably damaging	Het
Rnd3	T	A	2: 51,132,506	I175L	probably benign	Het
Rp1	C	A	1: 4,347,396	L1164F	probably damaging	Het
S100a7a	T	C	3: 90,655,635	V43A	probably benign	Het
Scaper	A	C	9: 55,602,918	Y1104*	probably null	Het
Scn2a	T	A	2: 65,764,594	V1929D	probably benign	Het
Scn3a	T	C	2: 65,529,441	N141S	possibly damaging	Het
Slc12a7	T	G	13: 73,801,008	L718R	probably damaging	Het
Slc15a2	T	C	16: 36,784,643		probably benign	Het
Slc35b3	G	A	13: 38,954,134	Q100*	probably null	Het
Slc9a5	T	A	8: 105,355,153	V170E	possibly damaging	Het
Snx5	T	G	2: 144,254,811	K278T	possibly damaging	Het
Sorbs2	T	C	8: 45,789,963		probably benign	Het
Stab1	C	T	14: 31,151,690	W1008*	probably null	Het
Stab2	C	T	10: 86,861,367		probably null	Het
Tacc3	A	G	5: 33,667,977	E377G	probably benign	Het
Tango6	T	C	8: 106,689,039	L164P	probably damaging	Het
Tbc1d12	T	A	19: 38,914,352	S570T	possibly damaging	Het
Thbs1	T	C	2: 118,114,355	F217L	probably damaging	Het
Tmbim6	T	A	15: 99,402,123	V40E	probably damaging	Het
Tmigd1	A	T	11: 76,910,160	N158Y	probably damaging	Het
Top3b	C	T	16: 16,892,777	R824*	probably null	Het
Tram1l1	A	T	3: 124,321,931	K247*	probably null	Het
Tsc2	T	C	17: 24,614,392	Y686C	probably damaging	Het
Tsga10	T	C	1: 37,819,599	Q218R	probably damaging	Het
Uba6	G	T	5: 86,140,423	A439D	probably damaging	Het
Ubn1	C	A	16: 5,077,294	P735T	probably damaging	Het
Usp40	A	G	1: 87,982,086	S549P	probably benign	Het
Utp20	T	C	10: 88,819,339	T176A	probably benign	Het
Utp4	T	G	8: 106,898,053		probably benign	Het
Xpo5	C	T	17: 46,207,927		probably benign	Het
Zfp979	A	T	4: 147,614,036	I72K	possibly damaging	Het

Other mutations in Cacna2d1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00091:Cacna2d1	APN	5	16212944	missense	probably damaging	1.00
IGL00470:Cacna2d1	APN	5	16246656	splice site	probably benign
IGL00495:Cacna2d1	APN	5	16370609	missense	probably benign	0.05
IGL00538:Cacna2d1	APN	5	16246785	nonsense	probably null
IGL00990:Cacna2d1	APN	5	15935069	missense	probably benign	0.23
IGL01079:Cacna2d1	APN	5	16370648	missense	probably benign	0.03
IGL01344:Cacna2d1	APN	5	16370631	missense	probably benign	0.26
IGL01597:Cacna2d1	APN	5	16326392	splice site	probably benign
IGL01645:Cacna2d1	APN	5	16012391	splice site	probably null
IGL01959:Cacna2d1	APN	5	16212897	missense	probably benign	0.00
IGL02397:Cacna2d1	APN	5	16320164	splice site	probably benign
IGL03152:Cacna2d1	APN	5	16322568	missense	probably benign	0.00
IGL03216:Cacna2d1	APN	5	16353842	missense	probably damaging	0.98
IGL03374:Cacna2d1	APN	5	16356823	missense	probably damaging	0.99
PIT4283001:Cacna2d1	UTSW	5	16302294	missense	probably benign	0.31
PIT4585001:Cacna2d1	UTSW	5	16326344	missense	probably damaging	1.00
R0158:Cacna2d1	UTSW	5	16361817	splice site	probably benign
R0457:Cacna2d1	UTSW	5	16267416	missense	probably damaging	1.00
R0477:Cacna2d1	UTSW	5	16194798	critical splice donor site	probably null
R0483:Cacna2d1	UTSW	5	16359027	missense	probably damaging	0.98
R0532:Cacna2d1	UTSW	5	16362273	missense	probably benign	0.13
R0552:Cacna2d1	UTSW	5	16328043	missense	probably damaging	1.00
R0924:Cacna2d1	UTSW	5	16365862	missense	possibly damaging	0.79
R0930:Cacna2d1	UTSW	5	16365862	missense	possibly damaging	0.79
R1144:Cacna2d1	UTSW	5	16322597	critical splice donor site	probably null
R1164:Cacna2d1	UTSW	5	16361876	critical splice donor site	probably null
R1398:Cacna2d1	UTSW	5	16357766	missense	possibly damaging	0.47
R1543:Cacna2d1	UTSW	5	16266718	missense	possibly damaging	0.62
R1573:Cacna2d1	UTSW	5	16370627	missense	probably damaging	1.00
R1633:Cacna2d1	UTSW	5	16320116	missense	probably damaging	1.00
R1673:Cacna2d1	UTSW	5	16299990	missense	probably damaging	1.00
R1750:Cacna2d1	UTSW	5	16264288	missense	probably benign	0.01
R1753:Cacna2d1	UTSW	5	16302354	missense	possibly damaging	0.95
R1966:Cacna2d1	UTSW	5	16333785	nonsense	probably null
R2163:Cacna2d1	UTSW	5	16362319	missense	probably damaging	1.00
R2258:Cacna2d1	UTSW	5	16357289	missense	probably damaging	1.00
R2870:Cacna2d1	UTSW	5	16312568	missense	probably damaging	1.00
R2870:Cacna2d1	UTSW	5	16312568	missense	probably damaging	1.00
R4303:Cacna2d1	UTSW	5	16302248	splice site	probably null
R4804:Cacna2d1	UTSW	5	16359208	missense	probably damaging	0.97
R5032:Cacna2d1	UTSW	5	16359070	missense	probably damaging	1.00
R5080:Cacna2d1	UTSW	5	16362396	critical splice donor site	probably null
R5466:Cacna2d1	UTSW	5	16246714	missense	probably damaging	1.00
R5469:Cacna2d1	UTSW	5	16352678	missense	probably damaging	0.99
R5564:Cacna2d1	UTSW	5	16312519	missense	probably damaging	1.00
R5655:Cacna2d1	UTSW	5	16302335	missense	probably damaging	1.00
R5688:Cacna2d1	UTSW	5	16358952	missense	probably damaging	0.99
R5729:Cacna2d1	UTSW	5	15935039	nonsense	probably null
R6005:Cacna2d1	UTSW	5	16361821	missense	probably damaging	1.00
R6343:Cacna2d1	UTSW	5	16322564	missense	probably benign	0.09
R6485:Cacna2d1	UTSW	5	16354657	missense	probably damaging	1.00
R6486:Cacna2d1	UTSW	5	16319450	splice site	probably null
R6625:Cacna2d1	UTSW	5	16362393	missense	probably null	1.00
R6700:Cacna2d1	UTSW	5	16365460	missense	probably damaging	1.00
R6706:Cacna2d1	UTSW	5	16326340	missense	probably damaging	1.00
R6711:Cacna2d1	UTSW	5	16300041	missense	probably damaging	1.00
R7025:Cacna2d1	UTSW	5	16352668	nonsense	probably null
R7035:Cacna2d1	UTSW	5	16246672	missense	probably damaging	1.00
R7086:Cacna2d1	UTSW	5	16349416	missense	probably damaging	1.00
R7110:Cacna2d1	UTSW	5	16357784	missense	probably damaging	0.99
R7268:Cacna2d1	UTSW	5	16370588	missense	probably damaging	0.99
R7310:Cacna2d1	UTSW	5	16314916	missense	probably damaging	1.00
R7471:Cacna2d1	UTSW	5	15934975	start gained	probably benign
R7608:Cacna2d1	UTSW	5	16359024	missense	probably damaging	1.00
R7712:Cacna2d1	UTSW	5	16362349	missense	probably damaging	0.98
R8014:Cacna2d1	UTSW	5	16342691	missense	possibly damaging	0.55
R8161:Cacna2d1	UTSW	5	16314937	missense	probably damaging	1.00
RF024:Cacna2d1	UTSW	5	16025776	missense	possibly damaging	0.80
Z1088:Cacna2d1	UTSW	5	16194763	missense	probably benign	0.02

Predicted Primers

PCR Primer
(F):5'- GGCTAATCCCGTGTATTTCAACCACT -3'
(R):5'- TGGATCTTCCCCATAAATGACTTCGGT -3'

Sequencing Primer
(F):5'- ttcaacccttcaccacctg -3'
(R):5'- ACTTCGGTTTATGATGTAACGC -3'

Posted On

2014-03-14