Mutagenetix > Incidental Mutation

Incidental Mutation 'R5734:Cacna1a'

451593

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

MMRRC Submission

043348-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.936) question?

Stock #

R5734 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

85065268-85366875 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 85310360 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Valine at position 1425 (M1425V)

Gene Model

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

AlphaFold

P97445

Predicted Effect

possibly damaging
Transcript: ENSMUST00000121390
AA Change: M1473V

PolyPhen 2 Score 0.876 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000112436
Gene: ENSMUSG00000034656
AA Change: M1473V

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 benign
Transcript: ENSMUST00000122053
AA Change: M1426V

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000114055
Gene: ENSMUSG00000034656
AA Change: M1426V

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: ENSMUST00000126302

Predicted Effect

probably damaging
Transcript: ENSMUST00000215756
AA Change: M1425V

PolyPhen 2 Score 0.965 (Sensitivity: 0.78; Specificity: 0.95)

Meta Mutation Damage Score

0.0923

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.9%
20x: 94.8%

Validation Efficiency

98% (61/62)

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: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4931429L15Rik	A	G	9: 46,215,303 (GRCm39)		probably benign	Het
Abcc9	A	G	6: 142,571,457 (GRCm39)		probably benign	Het
Adamts2	G	A	11: 50,679,494 (GRCm39)	G825R	probably damaging	Het
Adgre1	A	T	17: 57,750,990 (GRCm39)	R555W	probably benign	Het
Apob	T	A	12: 8,038,781 (GRCm39)	V398D	probably damaging	Het
Arid4b	A	G	13: 14,334,856 (GRCm39)	N355S	probably benign	Het
Asb3	G	T	11: 30,979,021 (GRCm39)	D143Y	probably damaging	Het
Birc6	G	A	17: 74,925,419 (GRCm39)		probably benign	Het
Capn9	A	G	8: 125,332,583 (GRCm39)	E474G	probably damaging	Het
Capza2	T	C	6: 17,660,764 (GRCm39)	S155P	probably damaging	Het
Ccdc125	A	G	13: 100,823,622 (GRCm39)	N202S	possibly damaging	Het
Ccn1	A	G	3: 145,354,023 (GRCm39)	C256R	probably damaging	Het
Chrm5	T	A	2: 112,310,445 (GRCm39)	T224S	probably benign	Het
Chtop	C	T	3: 90,409,422 (GRCm39)		probably null	Het
Clip1	T	C	5: 123,753,217 (GRCm39)		probably benign	Het
Dbx2	T	C	15: 95,552,604 (GRCm39)	T14A	possibly damaging	Het
Dcaf8	T	C	1: 172,000,478 (GRCm39)	V212A	possibly damaging	Het
Fam114a1	T	C	5: 65,166,389 (GRCm39)	M240T	probably damaging	Het
Fat1	T	C	8: 45,504,246 (GRCm39)	Y4580H	probably damaging	Het
Glipr1	G	A	10: 111,821,698 (GRCm39)	R200*	probably null	Het
Gm6408	A	T	5: 146,419,192 (GRCm39)	Y69F	probably benign	Het
Gpt2	T	C	8: 86,249,885 (GRCm39)	S456P	probably benign	Het
Kat8	T	C	7: 127,519,751 (GRCm39)	F225S	probably benign	Het
Lactb2	T	A	1: 13,730,611 (GRCm39)	N22Y	probably damaging	Het
Lin28a	A	T	4: 133,735,284 (GRCm39)	C67*	probably null	Het
Mtarc2	T	C	1: 184,564,786 (GRCm39)	E155G	probably benign	Het
Myoz3	G	A	18: 60,712,543 (GRCm39)	T104M	possibly damaging	Het
Nek9	C	T	12: 85,350,289 (GRCm39)	M928I	probably benign	Het
Nlrp9a	G	C	7: 26,270,065 (GRCm39)	A831P	probably damaging	Het
Nop53	T	C	7: 15,679,887 (GRCm39)		probably null	Het
Ofcc1	T	A	13: 40,241,325 (GRCm39)	T728S	probably damaging	Het
Pabpc4l	T	A	3: 46,401,124 (GRCm39)		probably null	Het
Rbm34	T	C	8: 127,696,880 (GRCm39)		probably null	Het
Relch	T	C	1: 105,631,608 (GRCm39)		probably benign	Het
Robo2	C	T	16: 74,149,672 (GRCm39)	C52Y	probably damaging	Het
Rpgr	G	A	X: 10,032,511 (GRCm39)	P857L	probably benign	Het
Scn2a	A	G	2: 65,548,066 (GRCm39)	Y57C	possibly damaging	Het
Selp	C	T	1: 163,971,460 (GRCm39)		probably benign	Het
Skp2	T	C	15: 9,139,566 (GRCm39)	D43G	possibly damaging	Het
Smad5	T	A	13: 56,871,617 (GRCm39)	S71T	probably damaging	Het
Sorcs1	G	T	19: 50,171,213 (GRCm39)	H892N	probably benign	Het
Sox6	C	T	7: 115,140,856 (GRCm39)		probably null	Het
St3gal1	A	T	15: 66,978,522 (GRCm39)	I333N	probably damaging	Het
Tex15	C	A	8: 34,036,364 (GRCm39)	Q97K	probably benign	Het
Tnxb	A	T	17: 34,917,884 (GRCm39)	T2266S	possibly damaging	Het
Tpbgl	C	A	7: 99,274,949 (GRCm39)	G303C	probably damaging	Het
Trat1	A	T	16: 48,555,304 (GRCm39)	S143T	possibly damaging	Het
Trpm8	T	A	1: 88,283,002 (GRCm39)	V763E	probably benign	Het
Ttc21a	G	A	9: 119,795,732 (GRCm39)	D1189N	probably benign	Het
Usp7	T	C	16: 8,519,845 (GRCm39)	N178D	possibly damaging	Het
Zfp217	T	C	2: 169,961,064 (GRCm39)	D421G	possibly damaging	Het
Zfp382	T	C	7: 29,833,855 (GRCm39)	F502S	probably 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
R3610:Cacna1a	UTSW	8	85,285,694 (GRCm39)	missense	probably damaging	1.00
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
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'- CAGGGTCCTCAAGCACTCA -3'
(R):5'- ACATTTGCTGTTGTTGTGTTCTCAA -3'

Sequencing Primer
(F):5'- TCCTCAAGCACTCAGTGGATG -3'
(R):5'- CTTCATACCTAGAGGCAGTCATG -3'

Posted On

2017-01-03