Mutagenetix > Incidental Mutation

Incidental Mutation 'IGL00425:Cacna2d2'

4818

Institutional Source

Australian Phenomics Network (link to record)

Gene Symbol

Cacna2d2

Ensembl Gene

ENSMUSG00000010066

Gene Name

calcium channel, voltage-dependent, alpha 2/delta subunit 2

Synonyms

a2d2

Accession Numbers

Essential gene?

Probably essential (E-score: 0.872) question?

Stock #

IGL00425

Quality Score

Status

Chromosome

Chromosomal Location

107276948-107406545 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 107404550 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 1114 (S1114P)

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: S1112P

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000010210
Gene: ENSMUSG00000010066
AA Change: S1112P

Domain	Start	End	E-Value	Type
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: S1118P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000082173
Gene: ENSMUSG00000010066
AA Change: S1118P

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000164988
AA Change: S1121P

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000130451
Gene: ENSMUSG00000010066
AA Change: S1121P

Domain	Start	End	E-Value	Type
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

possibly damaging
Transcript: ENSMUST00000166799
AA Change: S1121P

PolyPhen 2 Score 0.930 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000126029
Gene: ENSMUSG00000010066
AA Change: S1121P

Domain	Start	End	E-Value	Type
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

possibly damaging
Transcript: ENSMUST00000168532
AA Change: S1120P

PolyPhen 2 Score 0.930 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000132512
Gene: ENSMUSG00000010066
AA Change: S1120P

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000170737
AA Change: S1114P

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000125943
Gene: ENSMUSG00000010066
AA Change: S1114P

Domain	Start	End	E-Value	Type
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

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: 35 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam2	C	T	14: 66,311,498 (GRCm39)		probably null	Het
Adgrb2	A	T	4: 129,912,865 (GRCm39)	H1373L	probably benign	Het
Adgrf4	A	G	17: 42,977,547 (GRCm39)	S599P	probably damaging	Het
Atp9b	G	A	18: 80,961,103 (GRCm39)		probably benign	Het
Baiap2	A	G	11: 119,872,836 (GRCm39)	T125A	probably benign	Het
Barhl2	C	T	5: 106,603,365 (GRCm39)	A265T	possibly damaging	Het
Ccdc159	T	C	9: 21,840,765 (GRCm39)	S111P	possibly damaging	Het
Cd177	T	A	7: 24,459,176 (GRCm39)	T78S	possibly damaging	Het
Cdk5rap2	A	G	4: 70,321,709 (GRCm39)		probably null	Het
Cdkl3	C	A	11: 51,920,683 (GRCm39)	T462K	probably benign	Het
Chid1	A	C	7: 141,102,609 (GRCm39)	L208R	probably damaging	Het
Clca3b	A	G	3: 144,542,342 (GRCm39)	S487P	probably benign	Het
Col6a3	A	T	1: 90,709,748 (GRCm39)	L1816Q	unknown	Het
Dido1	A	G	2: 180,325,782 (GRCm39)	S469P	probably benign	Het
Dsg2	A	G	18: 20,734,826 (GRCm39)	N935D	probably benign	Het
Fbxw2	A	G	2: 34,702,961 (GRCm39)	I184T	probably benign	Het
Gbp9	T	C	5: 105,253,620 (GRCm39)	I32V	possibly damaging	Het
Hycc2	A	T	1: 58,579,412 (GRCm39)		probably benign	Het
Itgb8	G	A	12: 119,153,561 (GRCm39)	T318I	probably damaging	Het
Kcnb2	A	G	1: 15,781,236 (GRCm39)	S703G	probably benign	Het
Kif26b	A	T	1: 178,743,866 (GRCm39)	S1321C	probably damaging	Het
Klb	A	G	5: 65,529,717 (GRCm39)	N415S	possibly damaging	Het
Megf10	C	A	18: 57,373,700 (GRCm39)	A166D	probably damaging	Het
Mrm3	T	G	11: 76,135,319 (GRCm39)	S177A	probably damaging	Het
Nav3	A	G	10: 109,539,368 (GRCm39)	F2011S	probably benign	Het
Nipal1	C	T	5: 72,816,067 (GRCm39)	S30L	probably benign	Het
Ogdhl	T	C	14: 32,068,447 (GRCm39)	Y895H	probably damaging	Het
Pif1	A	G	9: 65,500,559 (GRCm39)	N495D	probably damaging	Het
Prrc2c	A	T	1: 162,548,182 (GRCm39)		probably null	Het
Pygl	T	C	12: 70,237,866 (GRCm39)	D724G	probably damaging	Het
Runx1t1	A	G	4: 13,835,663 (GRCm39)	D40G	probably benign	Het
Serhl	A	T	15: 82,989,838 (GRCm39)	D192V	possibly damaging	Het
Slc12a5	C	T	2: 164,825,201 (GRCm39)	A461V	probably damaging	Het
Tomm34	A	T	2: 163,900,582 (GRCm39)		probably benign	Het
Zfp54	A	G	17: 21,650,559 (GRCm39)	N45D	probably damaging	Het

Other mutations in Cacna2d2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00401:Cacna2d2	APN	9	107,392,072 (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
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

Posted On

2012-04-20