Mutagenetix > Incidental Mutation

Incidental Mutation 'R3610:Cacna1a'

269206

Institutional Source

Beutler Lab

Gene Symbol

Cacna1a

Ensembl Gene

ENSMUSG00000034656

Gene Name

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

Synonyms

Cacnl1a4, Ccha1a, SCA6, alpha1A, smrl, nmf352

Accession Numbers

Essential gene?

Probably essential (E-score: 0.924) question?

Stock #

R3610 (G1)

Quality Score

129

Status

Not validated

Chromosome

Chromosomal Location

85065268-85366875 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 85285694 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Serine at position 733 (R733S)

Ref Sequence

ENSEMBL: ENSMUSP00000114055 (fasta)

Gene Model

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

AlphaFold

P97445

Predicted Effect

probably damaging
Transcript: ENSMUST00000121390
AA Change: R780S

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000112436
Gene: ENSMUSG00000034656
AA Change: R780S

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: R733S

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

SMART Domains

Protein: ENSMUSP00000114055
Gene: ENSMUSG00000034656
AA Change: R733S

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

noncoding transcript
Transcript: ENSMUST00000129620

Predicted Effect

unknown
Transcript: ENSMUST00000215756
AA Change: R732S

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 94.6%

Validation Efficiency

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: 19 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsf2	C	A	11: 94,452,172 (GRCm39)	V457L	probably benign	Het
Cc2d2a	A	T	5: 43,869,668 (GRCm39)	E856D	probably damaging	Het
Cpeb2	T	C	5: 43,443,276 (GRCm39)	F989S	probably damaging	Het
Dcaf10	G	T	4: 45,372,962 (GRCm39)	E409*	probably null	Het
Ddx3y	T	C	Y: 1,263,928 (GRCm39)	N545S	probably null	Het
Eef2k	A	G	7: 120,488,458 (GRCm39)	S448G	probably benign	Het
Irf2bpl	T	C	12: 86,928,631 (GRCm39)	I681V	probably benign	Het
Kremen1	CGGG	CGGGGGG	11: 5,151,791 (GRCm39)		probably benign	Het
Morc2b	A	G	17: 33,355,252 (GRCm39)	V840A	probably damaging	Het
Pgap6	G	A	17: 26,337,860 (GRCm39)	V415I	probably benign	Het
Rcl1	A	G	19: 29,095,630 (GRCm39)	T72A	probably benign	Het
Robo1	T	C	16: 72,780,658 (GRCm39)	F796S	probably benign	Het
Rsf1	A	AAGGCGACGG	7: 97,229,111 (GRCm39)		probably null	Het
Setx	GTGGCT	GT	2: 29,044,073 (GRCm39)	1814	probably null	Het
Tars1	T	C	15: 11,392,990 (GRCm39)	Y152C	probably damaging	Het
Tmem184a	A	G	5: 139,793,710 (GRCm39)		probably null	Het
Tsc2	A	C	17: 24,841,524 (GRCm39)	I365S	possibly damaging	Het
Usp17la	G	A	7: 104,510,279 (GRCm39)	V295I	probably damaging	Het
Vim	A	T	2: 13,583,437 (GRCm39)	H253L	possibly damaging	Het

Other mutations in Cacna1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00507:Cacna1a	APN	8	85,297,837 (GRCm39)	nonsense	probably null
IGL00513:Cacna1a	APN	8	85,279,685 (GRCm39)	missense	probably damaging	1.00
IGL00569:Cacna1a	APN	8	85,189,343 (GRCm39)	missense	probably damaging	1.00
IGL00981:Cacna1a	APN	8	85,275,182 (GRCm39)	missense	probably damaging	1.00
IGL01122:Cacna1a	APN	8	85,341,422 (GRCm39)	critical splice donor site	probably null
IGL01309:Cacna1a	APN	8	85,249,657 (GRCm39)	missense	probably damaging	1.00
IGL01380:Cacna1a	APN	8	85,285,746 (GRCm39)	missense	probably damaging	1.00
IGL01638:Cacna1a	APN	8	85,298,456 (GRCm39)	missense	probably damaging	0.98
IGL01682:Cacna1a	APN	8	85,263,067 (GRCm39)	missense	possibly damaging	0.71
IGL02751:Cacna1a	APN	8	85,296,581 (GRCm39)	missense	probably damaging	1.00
IGL02904:Cacna1a	APN	8	85,306,149 (GRCm39)	missense	probably damaging	1.00
IGL03122:Cacna1a	APN	8	85,189,305 (GRCm39)	splice site	probably benign
totter	UTSW	8	85,315,382 (GRCm39)	missense	probably damaging	0.99
totter2	UTSW	8	85,315,382 (GRCm39)	missense	probably damaging	0.99
FR4340:Cacna1a	UTSW	8	85,365,352 (GRCm39)	small insertion	probably benign
FR4449:Cacna1a	UTSW	8	85,365,352 (GRCm39)	small insertion	probably benign
FR4449:Cacna1a	UTSW	8	85,365,349 (GRCm39)	small insertion	probably benign
FR4449:Cacna1a	UTSW	8	85,365,343 (GRCm39)	small insertion	probably benign
FR4548:Cacna1a	UTSW	8	85,365,346 (GRCm39)	small insertion	probably benign
FR4737:Cacna1a	UTSW	8	85,365,355 (GRCm39)	small insertion	probably benign
FR4737:Cacna1a	UTSW	8	85,365,349 (GRCm39)	small insertion	probably benign
FR4976:Cacna1a	UTSW	8	85,365,355 (GRCm39)	small insertion	probably benign
FR4976:Cacna1a	UTSW	8	85,365,346 (GRCm39)	small insertion	probably benign
IGL03134:Cacna1a	UTSW	8	85,285,716 (GRCm39)	missense	probably damaging	1.00
R0055:Cacna1a	UTSW	8	85,306,687 (GRCm39)	splice site	probably benign
R0118:Cacna1a	UTSW	8	85,262,712 (GRCm39)	missense	probably damaging	1.00
R0284:Cacna1a	UTSW	8	85,338,914 (GRCm39)	missense	probably damaging	1.00
R0581:Cacna1a	UTSW	8	85,328,565 (GRCm39)	missense	possibly damaging	0.83
R0607:Cacna1a	UTSW	8	85,356,460 (GRCm39)	missense	probably damaging	1.00
R1168:Cacna1a	UTSW	8	85,306,130 (GRCm39)	missense	probably damaging	1.00
R1183:Cacna1a	UTSW	8	85,306,846 (GRCm39)	missense	probably damaging	1.00
R1470:Cacna1a	UTSW	8	85,241,579 (GRCm39)	splice site	probably benign
R1503:Cacna1a	UTSW	8	85,328,575 (GRCm39)	missense	probably benign	0.23
R1522:Cacna1a	UTSW	8	85,360,062 (GRCm39)	missense	probably benign	0.00
R1835:Cacna1a	UTSW	8	85,307,986 (GRCm39)	splice site	probably null
R1862:Cacna1a	UTSW	8	85,142,559 (GRCm39)	missense	possibly damaging	0.80
R2148:Cacna1a	UTSW	8	85,356,304 (GRCm39)	missense	possibly damaging	0.71
R2237:Cacna1a	UTSW	8	85,360,394 (GRCm39)	critical splice donor site	probably null
R2567:Cacna1a	UTSW	8	85,276,354 (GRCm39)	missense	probably damaging	1.00
R2999:Cacna1a	UTSW	8	85,294,371 (GRCm39)	missense	probably damaging	1.00
R3025:Cacna1a	UTSW	8	85,306,854 (GRCm39)	critical splice donor site	probably null
R3702:Cacna1a	UTSW	8	85,344,475 (GRCm39)	missense	probably damaging	0.98
R3763:Cacna1a	UTSW	8	85,310,271 (GRCm39)	missense	possibly damaging	0.85
R4025:Cacna1a	UTSW	8	85,307,962 (GRCm39)	missense	probably damaging	1.00
R4026:Cacna1a	UTSW	8	85,307,962 (GRCm39)	missense	probably damaging	1.00
R4106:Cacna1a	UTSW	8	85,310,324 (GRCm39)	missense	possibly damaging	0.85
R4296:Cacna1a	UTSW	8	85,285,922 (GRCm39)	missense	probably damaging	1.00
R4664:Cacna1a	UTSW	8	85,328,396 (GRCm39)	nonsense	probably null
R4713:Cacna1a	UTSW	8	85,276,143 (GRCm39)	missense	probably damaging	1.00
R5223:Cacna1a	UTSW	8	85,313,824 (GRCm39)	missense	possibly damaging	0.94
R5408:Cacna1a	UTSW	8	85,276,336 (GRCm39)	missense	probably damaging	1.00
R5644:Cacna1a	UTSW	8	85,189,406 (GRCm39)	missense	probably damaging	1.00
R5734:Cacna1a	UTSW	8	85,310,360 (GRCm39)	missense	probably damaging	0.96
R5786:Cacna1a	UTSW	8	85,142,350 (GRCm39)	unclassified	probably benign
R5833:Cacna1a	UTSW	8	85,245,326 (GRCm39)	missense	probably damaging	1.00
R5886:Cacna1a	UTSW	8	85,249,651 (GRCm39)	missense	probably damaging	0.99
R6049:Cacna1a	UTSW	8	85,365,475 (GRCm39)	missense	probably damaging	0.96
R6054:Cacna1a	UTSW	8	85,283,414 (GRCm39)	missense	probably damaging	0.99
R6117:Cacna1a	UTSW	8	85,341,350 (GRCm39)	missense	probably damaging	1.00
R6149:Cacna1a	UTSW	8	85,296,581 (GRCm39)	missense	probably damaging	1.00
R6195:Cacna1a	UTSW	8	85,315,382 (GRCm39)	missense	probably damaging	0.99
R6233:Cacna1a	UTSW	8	85,315,382 (GRCm39)	missense	probably damaging	0.99
R6607:Cacna1a	UTSW	8	85,306,121 (GRCm39)	missense	probably damaging	1.00
R6753:Cacna1a	UTSW	8	85,306,834 (GRCm39)	missense	probably damaging	1.00
R6798:Cacna1a	UTSW	8	85,338,231 (GRCm39)	missense	probably damaging	1.00
R6831:Cacna1a	UTSW	8	85,297,860 (GRCm39)	missense	probably damaging	1.00
R6980:Cacna1a	UTSW	8	85,338,914 (GRCm39)	missense	possibly damaging	0.85
R7051:Cacna1a	UTSW	8	85,356,544 (GRCm39)	missense	possibly damaging	0.85
R7270:Cacna1a	UTSW	8	85,297,866 (GRCm39)	missense	probably damaging	1.00
R7409:Cacna1a	UTSW	8	85,260,031 (GRCm39)	missense	probably damaging	1.00
R7491:Cacna1a	UTSW	8	85,285,922 (GRCm39)	missense	possibly damaging	0.92
R7511:Cacna1a	UTSW	8	85,294,311 (GRCm39)	missense	possibly damaging	0.75
R7745:Cacna1a	UTSW	8	85,286,023 (GRCm39)	missense	probably benign	0.01
R7872:Cacna1a	UTSW	8	85,310,283 (GRCm39)	missense	probably damaging	1.00
R7899:Cacna1a	UTSW	8	85,320,802 (GRCm39)	missense	possibly damaging	0.72
R7986:Cacna1a	UTSW	8	85,365,408 (GRCm39)	missense	probably benign	0.02
R8126:Cacna1a	UTSW	8	85,359,881 (GRCm39)	missense	probably benign	0.02
R8266:Cacna1a	UTSW	8	85,285,848 (GRCm39)	missense	probably damaging	1.00
R8458:Cacna1a	UTSW	8	85,276,087 (GRCm39)	missense	probably damaging	1.00
R8504:Cacna1a	UTSW	8	85,365,370 (GRCm39)	missense	probably benign
R8530:Cacna1a	UTSW	8	85,339,043 (GRCm39)	critical splice donor site	probably null
R8750:Cacna1a	UTSW	8	85,285,784 (GRCm39)	missense	probably damaging	0.99
R8817:Cacna1a	UTSW	8	85,365,426 (GRCm39)	missense	probably benign	0.44
R8856:Cacna1a	UTSW	8	85,286,070 (GRCm39)	missense	probably benign	0.30
R8893:Cacna1a	UTSW	8	85,313,764 (GRCm39)	missense	probably benign	0.00
R9083:Cacna1a	UTSW	8	85,344,511 (GRCm39)	missense	probably benign	0.30
R9087:Cacna1a	UTSW	8	85,365,432 (GRCm39)	missense	probably benign	0.44
R9118:Cacna1a	UTSW	8	85,262,715 (GRCm39)	missense	probably damaging	1.00
R9133:Cacna1a	UTSW	8	85,276,152 (GRCm39)	missense	probably damaging	1.00
R9175:Cacna1a	UTSW	8	85,296,644 (GRCm39)	missense	probably damaging	0.99
R9233:Cacna1a	UTSW	8	85,271,283 (GRCm39)	missense	probably damaging	1.00
R9310:Cacna1a	UTSW	8	85,263,046 (GRCm39)	missense	probably damaging	1.00
R9331:Cacna1a	UTSW	8	85,142,446 (GRCm39)	missense	probably damaging	1.00
R9334:Cacna1a	UTSW	8	85,296,594 (GRCm39)	missense	probably damaging	1.00
R9531:Cacna1a	UTSW	8	85,320,801 (GRCm39)	missense	probably benign	0.02
R9532:Cacna1a	UTSW	8	85,338,246 (GRCm39)	missense	probably damaging	1.00
R9590:Cacna1a	UTSW	8	85,328,610 (GRCm39)	nonsense	probably null
R9710:Cacna1a	UTSW	8	85,320,808 (GRCm39)	missense	possibly damaging	0.74
RF029:Cacna1a	UTSW	8	85,365,353 (GRCm39)	small insertion	probably benign
X0022:Cacna1a	UTSW	8	85,360,328 (GRCm39)	missense	possibly damaging	0.53
Z1176:Cacna1a	UTSW	8	85,142,305 (GRCm39)	missense	unknown
Z1177:Cacna1a	UTSW	8	85,306,120 (GRCm39)	missense	probably damaging	1.00
Z1188:Cacna1a	UTSW	8	85,241,683 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GGTGTGAAACTGGCCTAGAG -3'
(R):5'- CGCACGGCTCTTGTTGGT -3'

Sequencing Primer
(F):5'- GAACCGATTGCAGATAGTTGCTC -3'
(R):5'- TGTTGTTGTTACGGTTCTCCTGC -3'

Posted On

2015-02-19