Mutagenetix > Incidental Mutations

Incidental Mutation 'R7409:Cacna1a'

574930

Institutional Source

Beutler Lab

Gene Symbol

Cacna1a

Ensembl Gene

ENSMUSG00000034656

Gene Name

calcium channel, voltage-dependent, P/Q type, alpha 1A subunit

Synonyms

Cacnl1a4, alpha1A, SCA6, nmf352, Ccha1a

MMRRC Submission

Accession Numbers

Is this an essential gene?

Probably essential (E-score: 0.925) question?

Stock #

R7409 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

84388440-84640246 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 84533402 bp

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 331 (D331E)

Ref Sequence

ENSEMBL: ENSMUSP00000112436 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000121390] [ENSMUST00000122053]

Predicted Effect

probably damaging
Transcript: ENSMUST00000121390
AA Change: D331E

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

SMART Domains

Protein: ENSMUSP00000112436
Gene: ENSMUSG00000034656
AA Change: D331E

Domain	Start	End	E-Value	Type
low complexity region	9	47	N/A	INTRINSIC
Pfam:Ion_trans	99	373	1.5e-69	PFAM
Pfam:Ion_trans	488	727	1.2e-54	PFAM
Pfam:PKD_channel	578	721	6.6e-8	PFAM
low complexity region	920	959	N/A	INTRINSIC
low complexity region	977	987	N/A	INTRINSIC
low complexity region	1074	1093	N/A	INTRINSIC
low complexity region	1143	1168	N/A	INTRINSIC
Pfam:Ion_trans	1194	1472	4.9e-64	PFAM
Pfam:Ion_trans	1516	1773	2.8e-64	PFAM
Pfam:GPHH	1775	1844	5.6e-39	PFAM
Ca_chan_IQ	1899	1933	1.8e-12	SMART
AT_hook	2053	2065	2.02e0	SMART
low complexity region	2101	2113	N/A	INTRINSIC
low complexity region	2153	2179	N/A	INTRINSIC
low complexity region	2213	2236	N/A	INTRINSIC
low complexity region	2253	2282	N/A	INTRINSIC
low complexity region	2314	2325	N/A	INTRINSIC
low complexity region	2342	2357	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000122053
AA Change: D284E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000114055
Gene: ENSMUSG00000034656
AA Change: D284E

Domain	Start	End	E-Value	Type
low complexity region	9	47	N/A	INTRINSIC
Pfam:Ion_trans	91	314	4.5e-58	PFAM
PDB:4DEX\|B	317	427	5e-45	PDB
Pfam:Ion_trans	476	668	6.4e-46	PFAM
Pfam:PKD_channel	530	675	7.7e-8	PFAM
low complexity region	873	912	N/A	INTRINSIC
low complexity region	930	940	N/A	INTRINSIC
low complexity region	1027	1046	N/A	INTRINSIC
low complexity region	1096	1121	N/A	INTRINSIC
Pfam:Ion_trans	1183	1414	2.8e-54	PFAM
Pfam:Ion_trans	1504	1714	3.2e-60	PFAM
Ca_chan_IQ	1852	1886	1.8e-12	SMART
AT_hook	2006	2018	2.02e0	SMART
low complexity region	2054	2066	N/A	INTRINSIC
low complexity region	2106	2132	N/A	INTRINSIC
low complexity region	2166	2189	N/A	INTRINSIC
low complexity region	2206	2235	N/A	INTRINSIC
low complexity region	2267	2278	N/A	INTRINSIC
low complexity region	2295	2310	N/A	INTRINSIC

Predicted Effect

Meta Mutation Damage Score

0.2258

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

98% (82/84)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]
PHENOTYPE: Homozygotes for different mutant alleles are characterized by variably severe wobbly gait beginning prior to weaning, ataxia, episodic dyskinesia, cerebellar atrophy, and absence epilepsy. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2610301B20Rik	T	A	4: 10,881,834	C94S	probably benign	Het
2610507B11Rik	G	T	11: 78,268,757	R544L	probably damaging	Het
Adgrb2	C	T	4: 130,019,069	A1329V	probably benign	Het
Aida	A	G	1: 183,318,874	T215A	probably benign	Het
Alpk2	A	G	18: 65,306,952	S457P	probably benign	Het
Ap4b1	G	A	3: 103,812,158	V63I	probably damaging	Het
Apaf1	A	G	10: 91,067,246	V182A	probably damaging	Het
B4galnt4	G	A	7: 141,067,003		probably null	Het
Carmil2	A	G	8: 105,692,791		probably null	Het
Cdkn1b	A	T	6: 134,921,317	Q133L	probably benign	Het
Cep192	G	C	18: 67,834,803	S786T	possibly damaging	Het
Cfap97	G	A	8: 46,192,696	R537H	probably benign	Het
Clpx	C	G	9: 65,324,247	A552G	possibly damaging	Het
Cryl1	G	A	14: 57,286,385	T240I	probably damaging	Het
Ddx60	C	A	8: 61,958,578	T488K	probably benign	Het
Dennd4b	A	G	3: 90,273,952	H805R	probably benign	Het
Dnmbp	T	C	19: 43,890,557	D25G	unknown	Het
Dysf	A	C	6: 84,149,682	D1293A	probably benign	Het
Efl1	T	C	7: 82,697,913	L549P	probably damaging	Het
Eif5	T	C	12: 111,540,263		probably benign	Het
Eva1c	A	G	16: 90,869,656	K156E	probably damaging	Het
Fbxw10	T	G	11: 62,876,780	V814G	possibly damaging	Het
Gfap	C	T	11: 102,894,532	R206Q	probably benign	Het
Gjb6	A	T	14: 57,124,153	L217*	probably null	Het
Gpatch11	T	A	17: 78,839,166	L80Q	probably damaging	Het
Gramd1b	T	C	9: 40,327,431	Q225R	probably damaging	Het
Gsdmc2	A	G	15: 63,833,346	S173P	possibly damaging	Het
Hars	C	G	18: 36,770,113	R388P	probably damaging	Het
Ighm	C	T	12: 113,422,232	R129H		Het
Igsf9	A	G	1: 172,495,274	I602V	probably benign	Het
Inpp4b	T	G	8: 81,952,685		probably null	Het
Itch	C	A	2: 155,199,382	T450K	probably damaging	Het
Kcnq1	T	C	7: 143,109,415	F20L	unknown	Het
Kmt2d	G	T	15: 98,855,354	A153E	probably damaging	Het
Macf1	T	A	4: 123,504,470	N750I	probably damaging	Het
Marveld2	T	A	13: 100,611,476	H365L	probably damaging	Het
Med13l	T	A	5: 118,754,321	D1936E	probably benign	Het
Mettl8	A	T	2: 70,973,343	V200E	probably damaging	Het
Mrgbp	T	G	2: 180,585,342	S157A	possibly damaging	Het
Mrps35	A	G	6: 147,055,983	T169A	possibly damaging	Het
Mycbp2	A	T	14: 103,288,744	Y551N	probably damaging	Het
Myo18b	T	C	5: 112,874,105	R474G	probably benign	Het
Nfx1	T	A	4: 41,021,830	S979R	possibly damaging	Het
Nlrp1a	T	C	11: 71,122,808	T539A	probably benign	Het
Oca2	T	A	7: 56,414,397	D713E	probably benign	Het
Olfr433	T	A	1: 174,042,533	H194Q	probably benign	Het
Olfr60	C	T	7: 140,345,405	V195I	probably benign	Het
Olfr768	A	G	10: 129,093,212	I254T	probably damaging	Het
Olfr816	A	T	10: 129,912,251	V9D	possibly damaging	Het
Omt2b	A	C	9: 78,328,612	Y73S	probably benign	Het
Pde11a	G	T	2: 76,005,984	Q20K		Het
Peg10	CCACATCAGGATCCACATCAGGATGCACATCAGCATCAGGATCCCCATCAGGATGCACATCAGGATCCACATCAGGATGCACATCAG	CCACATCAGGATCCACATCAGGATGCACATCAG	6: 4,756,398		probably benign	Het
Phrf1	C	A	7: 141,259,292	T800K	unknown	Het
Pramel4	T	C	4: 144,068,491	S486P	probably benign	Het
Proc	T	C	18: 32,127,460	D204G	probably benign	Het
Rasgrp3	T	A	17: 75,516,416	I494N	possibly damaging	Het
Samm50	A	G	15: 84,197,030	D53G	probably benign	Het
Satb1	T	C	17: 51,809,189	D22G	possibly damaging	Het
Scarf2	T	C	16: 17,807,054	S658P	probably damaging	Het
Sfta2	T	A	17: 35,614,518	I29K	unknown	Het
Slc15a4	A	T	5: 127,604,678	S292T	probably benign	Het
Slc37a1	C	T	17: 31,340,263	T439I	probably damaging	Het
Slc4a9	C	A	18: 36,530,805	P294Q	probably damaging	Het
Slc52a3	T	C	2: 152,004,166	S16P	probably damaging	Het
Slc6a15	A	G	10: 103,408,302	I468V	probably benign	Het
Spag17	T	C	3: 100,027,231	S610P	possibly damaging	Het
Spag17	A	T	3: 100,034,159	D738V	probably benign	Het
Ssbp4	T	C	8: 70,597,967	R269G	unknown	Het
Tbl1xr1	A	G	3: 22,203,190	T406A	possibly damaging	Het
Tep1	A	T	14: 50,866,855	V194D	possibly damaging	Het
Thbs4	A	T	13: 92,773,259	C343*	probably null	Het
Tmed10	A	T	12: 85,344,291	S158T	possibly damaging	Het
Trbv3	T	A	6: 41,048,590	V38E	probably damaging	Het
Ttc6	T	C	12: 57,696,986	M1258T	probably damaging	Het
Ttn	T	C	2: 76,758,976	D21281G	probably damaging	Het
Twistnb	T	G	12: 33,436,989	C150W	possibly damaging	Het
Usp54	T	C	14: 20,552,245	R1346G	probably damaging	Het
Vmn2r8	C	A	5: 108,808,583	E58*	probably null	Het
Vps13d	C	T	4: 145,141,254	E2009K		Het
Vps33b	T	C	7: 80,285,269	I320T	probably damaging	Het
Vwa8	A	C	14: 78,982,234		probably null	Het
Ythdf1	T	C	2: 180,911,993	Y143C	probably damaging	Het
Zfp213	C	T	17: 23,559,629		probably null	Het
Zfp219	A	T	14: 52,007,113	Y536*	probably null	Het

Other mutations in Cacna1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00507:Cacna1a	APN	8	84571208	nonsense	probably null
IGL00513:Cacna1a	APN	8	84553056	missense	probably damaging	1.00
IGL00569:Cacna1a	APN	8	84462714	missense	probably damaging	1.00
IGL00981:Cacna1a	APN	8	84548553	missense	probably damaging	1.00
IGL01122:Cacna1a	APN	8	84614793	critical splice donor site	probably null
IGL01309:Cacna1a	APN	8	84523028	missense	probably damaging	1.00
IGL01380:Cacna1a	APN	8	84559117	missense	probably damaging	1.00
IGL01638:Cacna1a	APN	8	84571827	missense	probably damaging	0.98
IGL01682:Cacna1a	APN	8	84536438	missense	possibly damaging	0.71
IGL02751:Cacna1a	APN	8	84569952	missense	probably damaging	1.00
IGL02904:Cacna1a	APN	8	84579520	missense	probably damaging	1.00
IGL03122:Cacna1a	APN	8	84462676	splice site	probably benign
totter	UTSW	8	84588753	missense	probably damaging	0.99
totter2	UTSW	8	84588753	missense	probably damaging	0.99
FR4340:Cacna1a	UTSW	8	84638723	small insertion	probably benign
FR4449:Cacna1a	UTSW	8	84638714	small insertion	probably benign
FR4449:Cacna1a	UTSW	8	84638720	small insertion	probably benign
FR4449:Cacna1a	UTSW	8	84638723	small insertion	probably benign
FR4548:Cacna1a	UTSW	8	84638717	small insertion	probably benign
FR4737:Cacna1a	UTSW	8	84638720	small insertion	probably benign
FR4737:Cacna1a	UTSW	8	84638726	small insertion	probably benign
FR4976:Cacna1a	UTSW	8	84638717	small insertion	probably benign
FR4976:Cacna1a	UTSW	8	84638726	small insertion	probably benign
IGL03134:Cacna1a	UTSW	8	84559087	missense	probably damaging	1.00
R0055:Cacna1a	UTSW	8	84580058	splice site	probably benign
R0118:Cacna1a	UTSW	8	84536083	missense	probably damaging	1.00
R0284:Cacna1a	UTSW	8	84612285	missense	probably damaging	1.00
R0581:Cacna1a	UTSW	8	84601936	missense	possibly damaging	0.83
R0607:Cacna1a	UTSW	8	84629831	missense	probably damaging	1.00
R1168:Cacna1a	UTSW	8	84579501	missense	probably damaging	1.00
R1183:Cacna1a	UTSW	8	84580217	missense	probably damaging	1.00
R1470:Cacna1a	UTSW	8	84514950	splice site	probably benign
R1503:Cacna1a	UTSW	8	84601946	missense	probably benign	0.23
R1522:Cacna1a	UTSW	8	84633433	missense	probably benign	0.00
R1835:Cacna1a	UTSW	8	84581357	splice site	probably null
R1862:Cacna1a	UTSW	8	84415930	missense	possibly damaging	0.80
R2148:Cacna1a	UTSW	8	84629675	missense	possibly damaging	0.71
R2237:Cacna1a	UTSW	8	84633765	critical splice donor site	probably null
R2567:Cacna1a	UTSW	8	84549725	missense	probably damaging	1.00
R2999:Cacna1a	UTSW	8	84567742	missense	probably damaging	1.00
R3025:Cacna1a	UTSW	8	84580225	critical splice donor site	probably null
R3610:Cacna1a	UTSW	8	84559065	missense	probably damaging	1.00
R3702:Cacna1a	UTSW	8	84617846	missense	probably damaging	0.98
R3763:Cacna1a	UTSW	8	84583642	missense	possibly damaging	0.85
R4025:Cacna1a	UTSW	8	84581333	missense	probably damaging	1.00
R4026:Cacna1a	UTSW	8	84581333	missense	probably damaging	1.00
R4106:Cacna1a	UTSW	8	84583695	missense	possibly damaging	0.85
R4296:Cacna1a	UTSW	8	84559293	missense	probably damaging	1.00
R4664:Cacna1a	UTSW	8	84601767	nonsense	probably null
R4713:Cacna1a	UTSW	8	84549514	missense	probably damaging	1.00
R5223:Cacna1a	UTSW	8	84587195	missense	possibly damaging	0.94
R5408:Cacna1a	UTSW	8	84549707	missense	probably damaging	1.00
R5644:Cacna1a	UTSW	8	84462777	missense	probably damaging	1.00
R5734:Cacna1a	UTSW	8	84583731	missense	probably damaging	0.96
R5786:Cacna1a	UTSW	8	84415721	unclassified	probably benign
R5833:Cacna1a	UTSW	8	84518697	missense	probably damaging	1.00
R5886:Cacna1a	UTSW	8	84523022	missense	probably damaging	0.99
R6049:Cacna1a	UTSW	8	84638846	missense	probably damaging	0.96
R6054:Cacna1a	UTSW	8	84556785	missense	probably damaging	0.99
R6117:Cacna1a	UTSW	8	84614721	missense	probably damaging	1.00
R6149:Cacna1a	UTSW	8	84569952	missense	probably damaging	1.00
R6195:Cacna1a	UTSW	8	84588753	missense	probably damaging	0.99
R6233:Cacna1a	UTSW	8	84588753	missense	probably damaging	0.99
R6607:Cacna1a	UTSW	8	84579492	missense	probably damaging	1.00
R6753:Cacna1a	UTSW	8	84580205	missense	probably damaging	1.00
R6798:Cacna1a	UTSW	8	84611602	missense	probably damaging	1.00
R6831:Cacna1a	UTSW	8	84571231	missense	probably damaging	1.00
R6980:Cacna1a	UTSW	8	84612285	missense	possibly damaging	0.85
R7051:Cacna1a	UTSW	8	84629915	missense	possibly damaging	0.85
R7270:Cacna1a	UTSW	8	84571237	missense	probably damaging	1.00
R7491:Cacna1a	UTSW	8	84559293	missense	possibly damaging	0.92
R7511:Cacna1a	UTSW	8	84567682	missense	possibly damaging	0.75
R7745:Cacna1a	UTSW	8	84559394	missense	probably benign	0.01
R7872:Cacna1a	UTSW	8	84583654	missense	probably damaging	1.00
R7899:Cacna1a	UTSW	8	84594173	missense	possibly damaging	0.72
R7955:Cacna1a	UTSW	8	84583654	missense	probably damaging	1.00
R7982:Cacna1a	UTSW	8	84594173	missense	possibly damaging	0.72
RF029:Cacna1a	UTSW	8	84638724	small insertion	probably benign
X0022:Cacna1a	UTSW	8	84633699	missense	possibly damaging	0.53
Z1176:Cacna1a	UTSW	8	84415676
Z1177:Cacna1a	UTSW	8	84579491

Predicted Primers

PCR Primer
(F):5'- GTGACATGAGACAGCTTTGTCC -3'
(R):5'- CTTGCTGACTGAAACCAGGAAG -3'

Sequencing Primer
(F):5'- GTATCTTGGTGATAGCCCCCAAAC -3'
(R):5'- CTGAAACCAGGAAGGAAGTTTCTTC -3'

Posted On

2019-10-07