Mutagenetix > Incidental Mutation

Incidental Mutation 'R8251:Cacna1s'

640218

Institutional Source

Beutler Lab

Gene Symbol

Cacna1s

Ensembl Gene

ENSMUSG00000026407

Gene Name

calcium channel, voltage-dependent, L type, alpha 1S subunit

Synonyms

sj, mdg, muscle dysgenesis, DHPR alpha1s, Cav1.1, Cchl1a3, fmd

MMRRC Submission

Accession Numbers

Genbank: NM_001081023; MGI: 88294

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R8251 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

136052750-136119822 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 136086723 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glycine to Tryptophan at position 623 (G623W)

Ref Sequence

ENSEMBL: ENSMUSP00000107699 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000112064] [ENSMUST00000112068] [ENSMUST00000160641] [ENSMUST00000161865]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000112064
AA Change: G623W

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

SMART Domains

Protein: ENSMUSP00000107695
Gene: ENSMUSG00000026407
AA Change: G623W

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	50	345	4.3e-68	PFAM
Pfam:Ion_trans	431	672	4.5e-56	PFAM
Pfam:PKD_channel	516	667	1.9e-7	PFAM
low complexity region	675	685	N/A	INTRINSIC
low complexity region	740	756	N/A	INTRINSIC
Pfam:Ion_trans	798	1076	2.6e-65	PFAM
Pfam:Ion_trans	1117	1392	1.2e-71	PFAM
Pfam:PKD_channel	1126	1387	8.4e-13	PFAM
Pfam:GPHH	1394	1463	2.3e-38	PFAM
Ca_chan_IQ	1515	1548	3.71e-14	SMART
low complexity region	1657	1669	N/A	INTRINSIC
Pfam:CAC1F_C	1756	1845	2.8e-8	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000112068
AA Change: G623W

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

SMART Domains

Protein: ENSMUSP00000107699
Gene: ENSMUSG00000026407
AA Change: G623W

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	88	333	9.1e-57	PFAM
PDB:4DEY\|B	334	417	1e-20	PDB
Pfam:Ion_trans	466	660	3.7e-46	PFAM
Pfam:PKD_channel	513	667	6.7e-7	PFAM
low complexity region	675	685	N/A	INTRINSIC
low complexity region	740	756	N/A	INTRINSIC
low complexity region	804	818	N/A	INTRINSIC
Pfam:Ion_trans	834	1064	3.9e-53	PFAM
Pfam:Ion_trans	1152	1361	6.7e-66	PFAM
Pfam:PKD_channel	1201	1368	8.4e-10	PFAM
Blast:EFh	1382	1410	5e-8	BLAST
Ca_chan_IQ	1496	1529	3.71e-14	SMART
low complexity region	1638	1650	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000160641
AA Change: G623W

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

SMART Domains

Protein: ENSMUSP00000125278
Gene: ENSMUSG00000026407
AA Change: G623W

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	88	333	9.3e-57	PFAM
PDB:4DEY\|B	334	417	1e-20	PDB
Pfam:Ion_trans	466	660	3.8e-46	PFAM
Pfam:PKD_channel	513	667	6.7e-7	PFAM
low complexity region	675	685	N/A	INTRINSIC
low complexity region	740	756	N/A	INTRINSIC
low complexity region	804	818	N/A	INTRINSIC
Pfam:Ion_trans	834	1064	4e-53	PFAM
Pfam:PKD_channel	1126	1387	6.1e-12	PFAM
Pfam:Ion_trans	1152	1380	9e-65	PFAM
Blast:EFh	1401	1429	5e-8	BLAST
Ca_chan_IQ	1515	1548	3.71e-14	SMART
low complexity region	1657	1669	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000161865
AA Change: G376W

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

SMART Domains

Protein: ENSMUSP00000125262
Gene: ENSMUSG00000026407
AA Change: G376W

Domain	Start	End	E-Value	Type
Pfam:Ion_trans	3	98	1.1e-21	PFAM
Pfam:Ion_trans	184	425	3.3e-56	PFAM
Pfam:PKD_channel	267	420	1.8e-7	PFAM
low complexity region	428	438	N/A	INTRINSIC
low complexity region	493	509	N/A	INTRINSIC
Pfam:Ion_trans	551	829	1.9e-65	PFAM
Pfam:Ion_trans	870	1126	5.4e-72	PFAM
Pfam:PKD_channel	954	1121	7.2e-10	PFAM
Pfam:GPHH	1128	1197	1.8e-38	PFAM
Ca_chan_IQ	1249	1282	3.71e-14	SMART
low complexity region	1391	1403	N/A	INTRINSIC

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.5%

Validation Efficiency

100% (50/50)

MGI Phenotype

Strain: 1856326
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutants show edema and failure of myoblast differentiation by day 13 of embryonic development and die perinatally. All muscles degenerate and additional secondary anomalies of the skeleton, short jaw, and cleft palate are seen. [provided by MGI curators]

Allele List at MGI

All alleles(4) : Targeted(3) Spontaneous(1)

Other mutations in this stock

Total: 49 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700019O17Rik	A	G	1: 86,427,214	N282D	probably benign	Het
Acad11	A	T	9: 104,091,707	D463V	possibly damaging	Het
Adamtsl4	C	T	3: 95,684,574	R68Q	probably damaging	Het
Ankrd12	A	T	17: 65,984,559	M1293K	possibly damaging	Het
Arhgap21	T	C	2: 20,849,410	T1724A	probably benign	Het
Cenpe	T	A	3: 135,251,684		probably null	Het
Cep85l	A	T	10: 53,281,354	I751N	probably damaging	Het
Corin	T	A	5: 72,356,926	D468V	probably damaging	Het
Ctsr	A	G	13: 61,162,778	V51A	probably damaging	Het
Dnah14	A	C	1: 181,664,865	E1630A	probably damaging	Het
Dsg4	C	A	18: 20,471,164	A896E	probably damaging	Het
Ear2	T	C	14: 44,103,020	L45P	probably benign	Het
Fam132a	T	C	4: 155,966,459	I295T	probably damaging	Het
Fshr	T	G	17: 89,200,485	D43A	probably benign	Het
Gata6	G	A	18: 11,054,670	G200S	probably benign	Het
Gnaq	T	A	19: 16,335,055	M227K	probably damaging	Het
Ifit1bl1	T	C	19: 34,594,832	Q75R	possibly damaging	Het
Impg2	A	G	16: 56,259,597	E479G	possibly damaging	Het
Ints7	C	T	1: 191,621,433	P957L	unknown	Het
Jmjd1c	T	C	10: 67,239,289	V73A	noncoding transcript	Het
Kansl1	A	G	11: 104,424,360	I284T	probably benign	Het
Kcnj9	A	G	1: 172,326,522	S12P	probably benign	Het
Krt16	A	G	11: 100,248,370		probably null	Het
Lrguk	A	T	6: 34,116,439	T632S	probably benign	Het
Man2b1	G	A	8: 85,095,129	V687M	probably damaging	Het
Mroh5	T	C	15: 73,783,153	E653G	probably benign	Het
Nabp1	A	T	1: 51,477,578	S44T	probably benign	Het
Nt5dc3	C	A	10: 86,820,227	H256Q	probably damaging	Het
Olfr1254	A	T	2: 89,789,223	I43N	probably damaging	Het
Olfr344	A	C	2: 36,569,455	N286H	probably damaging	Het
Olfr469	A	G	7: 107,822,569	I300T	probably damaging	Het
Pkd2	T	C	5: 104,498,487	V720A	probably benign	Het
Pnpla6	T	A	8: 3,532,399	N706K	probably benign	Het
Polr1b	C	A	2: 129,123,166	P724Q	probably damaging	Het
Rbpjl	A	G	2: 164,413,934	E366G	probably damaging	Het
Runx1t1	A	G	4: 13,846,947	T244A	possibly damaging	Het
Slitrk3	C	T	3: 73,049,396	R681H	possibly damaging	Het
Slu7	A	G	11: 43,439,301	Y185C	probably damaging	Het
Snupn	T	A	9: 56,980,853	F231L	probably damaging	Het
Srpk2	G	A	5: 23,524,268	P458S	probably benign	Het
St3gal5	T	A	6: 72,149,160	F330I	probably benign	Het
Taf3	T	C	2: 9,918,151	D878G	possibly damaging	Het
Tmem126a	T	C	7: 90,450,886	I150V	probably benign	Het
Tmem2	T	C	19: 21,807,401	V416A	possibly damaging	Het
Trbv21	A	G	6: 41,202,606		probably benign	Het
Vmn2r70	A	T	7: 85,565,978	L116*	probably null	Het
Vps36	A	G	8: 22,192,916	T16A	probably benign	Het
Wdr17	C	A	8: 54,657,232	G837W	probably damaging	Het
Zfp397	T	C	18: 23,960,304	V282A	probably benign	Het

Other mutations in Cacna1s

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00336:Cacna1s	APN	1	136084273	nonsense	probably null
IGL00517:Cacna1s	APN	1	136087339	missense	probably damaging	1.00
IGL01316:Cacna1s	APN	1	136118964	missense	probably benign	0.01
IGL01348:Cacna1s	APN	1	136075152	missense	possibly damaging	0.95
IGL01739:Cacna1s	APN	1	136097132	critical splice donor site	probably null
IGL01773:Cacna1s	APN	1	136118753	missense	probably benign	0.32
IGL02056:Cacna1s	APN	1	136119000	missense	probably benign
IGL02262:Cacna1s	APN	1	136108129	missense	probably damaging	0.98
IGL02324:Cacna1s	APN	1	136075176	splice site	probably benign
IGL02352:Cacna1s	APN	1	136093252	splice site	probably benign
IGL02359:Cacna1s	APN	1	136093252	splice site	probably benign
IGL02370:Cacna1s	APN	1	136085347	missense	probably damaging	1.00
IGL02377:Cacna1s	APN	1	136068994	missense	probably damaging	1.00
IGL02474:Cacna1s	APN	1	136118380	missense	probably benign
IGL02606:Cacna1s	APN	1	136079519	missense	probably damaging	0.99
IGL02833:Cacna1s	APN	1	136071005	missense	probably benign	0.03
IGL02974:Cacna1s	APN	1	136092617	missense	possibly damaging	0.78
IGL03064:Cacna1s	APN	1	136111993	missense	probably damaging	1.00
IGL03093:Cacna1s	APN	1	136116064	missense	probably benign	0.00
IGL03286:Cacna1s	APN	1	136077659	missense	probably benign
brookstone	UTSW	1	136092694	missense	probably benign	0.01
flyfish	UTSW	1	136116061	missense	probably benign	0.21
forelle	UTSW	1	136095858	missense	probably damaging	0.99
river	UTSW	1	136105844	missense	possibly damaging	0.88
stream	UTSW	1	136105814	missense	probably damaging	1.00
BB009:Cacna1s	UTSW	1	136084359	missense	probably damaging	0.99
BB019:Cacna1s	UTSW	1	136084359	missense	probably damaging	0.99
G1Funyon:Cacna1s	UTSW	1	136073441	unclassified	probably benign
N/A:Cacna1s	UTSW	1	136073509	missense	probably benign	0.00
R0030:Cacna1s	UTSW	1	136094989	critical splice donor site	probably null
R0030:Cacna1s	UTSW	1	136094989	critical splice donor site	probably null
R0097:Cacna1s	UTSW	1	136100622	missense	possibly damaging	0.79
R0097:Cacna1s	UTSW	1	136100622	missense	possibly damaging	0.79
R0240:Cacna1s	UTSW	1	136073496	unclassified	probably benign
R0255:Cacna1s	UTSW	1	136118806	missense	possibly damaging	0.93
R0302:Cacna1s	UTSW	1	136100604	missense	probably benign	0.01
R0319:Cacna1s	UTSW	1	136070717	missense	probably damaging	0.99
R0411:Cacna1s	UTSW	1	136113303	missense	probably damaging	1.00
R0413:Cacna1s	UTSW	1	136098209	missense	probably benign	0.00
R0482:Cacna1s	UTSW	1	136113394	missense	probably benign
R0491:Cacna1s	UTSW	1	136089008	splice site	probably benign
R0518:Cacna1s	UTSW	1	136076859	missense	probably benign
R0717:Cacna1s	UTSW	1	136098291	missense	probably damaging	1.00
R0725:Cacna1s	UTSW	1	136098526	splice site	probably benign
R0815:Cacna1s	UTSW	1	136112957	missense	possibly damaging	0.95
R1384:Cacna1s	UTSW	1	136094971	missense	probably benign	0.02
R1518:Cacna1s	UTSW	1	136098551	missense	probably damaging	1.00
R1548:Cacna1s	UTSW	1	136110937	missense	probably damaging	1.00
R1725:Cacna1s	UTSW	1	136098623	missense	probably damaging	1.00
R1728:Cacna1s	UTSW	1	136118716	missense	probably benign
R1729:Cacna1s	UTSW	1	136118716	missense	probably benign
R1730:Cacna1s	UTSW	1	136118716	missense	probably benign
R1739:Cacna1s	UTSW	1	136118716	missense	probably benign
R1762:Cacna1s	UTSW	1	136118716	missense	probably benign
R1783:Cacna1s	UTSW	1	136118716	missense	probably benign
R1784:Cacna1s	UTSW	1	136118716	missense	probably benign
R1785:Cacna1s	UTSW	1	136118716	missense	probably benign
R1800:Cacna1s	UTSW	1	136076854	missense	probably benign
R1924:Cacna1s	UTSW	1	136089017	splice site	probably null
R1969:Cacna1s	UTSW	1	136119095	missense	probably benign	0.42
R2072:Cacna1s	UTSW	1	136079504	missense	probably benign
R2380:Cacna1s	UTSW	1	136095848	missense	probably damaging	1.00
R3110:Cacna1s	UTSW	1	136075093	nonsense	probably null
R3112:Cacna1s	UTSW	1	136075093	nonsense	probably null
R3151:Cacna1s	UTSW	1	136105794	missense	probably damaging	1.00
R3696:Cacna1s	UTSW	1	136105814	missense	probably damaging	1.00
R3722:Cacna1s	UTSW	1	136069042	missense	possibly damaging	0.77
R3804:Cacna1s	UTSW	1	136107018	missense	possibly damaging	0.85
R3813:Cacna1s	UTSW	1	136085347	missense	probably damaging	1.00
R3905:Cacna1s	UTSW	1	136084269	missense	probably damaging	0.99
R3907:Cacna1s	UTSW	1	136084269	missense	probably damaging	0.99
R3909:Cacna1s	UTSW	1	136084269	missense	probably damaging	0.99
R4170:Cacna1s	UTSW	1	136108195	missense	probably damaging	1.00
R4329:Cacna1s	UTSW	1	136119033	missense	probably benign	0.00
R4485:Cacna1s	UTSW	1	136076852	missense	probably damaging	1.00
R4581:Cacna1s	UTSW	1	136070970	splice site	probably null
R4719:Cacna1s	UTSW	1	136118652	splice site	probably benign
R4816:Cacna1s	UTSW	1	136115269	missense	possibly damaging	0.89
R4909:Cacna1s	UTSW	1	136079604	missense	probably damaging	0.99
R4917:Cacna1s	UTSW	1	136101564	critical splice donor site	probably null
R5296:Cacna1s	UTSW	1	136095785	missense	probably benign	0.11
R5411:Cacna1s	UTSW	1	136105811	missense	probably benign	0.09
R5503:Cacna1s	UTSW	1	136086742	missense	probably damaging	1.00
R5533:Cacna1s	UTSW	1	136098375	critical splice donor site	probably null
R5714:Cacna1s	UTSW	1	136112066	missense	probably benign	0.44
R5775:Cacna1s	UTSW	1	136108122	missense	probably damaging	1.00
R5814:Cacna1s	UTSW	1	136107142	missense	probably benign	0.31
R5820:Cacna1s	UTSW	1	136079604	missense	probably damaging	1.00
R5822:Cacna1s	UTSW	1	136112078	missense	probably damaging	1.00
R5877:Cacna1s	UTSW	1	136100667	missense	probably damaging	0.99
R5923:Cacna1s	UTSW	1	136076822	missense	possibly damaging	0.79
R6021:Cacna1s	UTSW	1	136106487	missense	probably benign	0.15
R6037:Cacna1s	UTSW	1	136070967	missense	possibly damaging	0.90
R6037:Cacna1s	UTSW	1	136070967	missense	possibly damaging	0.90
R6056:Cacna1s	UTSW	1	136105836	missense	probably damaging	1.00
R6143:Cacna1s	UTSW	1	136076758	missense	probably damaging	0.99
R6222:Cacna1s	UTSW	1	136104622	missense	probably benign	0.00
R6237:Cacna1s	UTSW	1	136105844	missense	possibly damaging	0.88
R6274:Cacna1s	UTSW	1	136089045	missense	probably benign	0.02
R6609:Cacna1s	UTSW	1	136113391	missense	probably benign	0.30
R6626:Cacna1s	UTSW	1	136094965	missense	probably damaging	1.00
R6838:Cacna1s	UTSW	1	136084437	missense	possibly damaging	0.91
R6848:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6849:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6850:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6851:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6868:Cacna1s	UTSW	1	136092694	missense	probably benign	0.01
R6879:Cacna1s	UTSW	1	136115959	missense	probably benign	0.12
R6893:Cacna1s	UTSW	1	136077693	missense	probably benign	0.05
R7017:Cacna1s	UTSW	1	136095858	missense	probably damaging	0.99
R7228:Cacna1s	UTSW	1	136071059	missense	possibly damaging	0.90
R7283:Cacna1s	UTSW	1	136073708	missense	probably damaging	1.00
R7357:Cacna1s	UTSW	1	136071021	missense	probably damaging	0.99
R7385:Cacna1s	UTSW	1	136092633	missense	probably damaging	0.99
R7421:Cacna1s	UTSW	1	136086802	missense	probably damaging	1.00
R7505:Cacna1s	UTSW	1	136085449	nonsense	probably null
R7519:Cacna1s	UTSW	1	136070756	missense	probably damaging	0.99
R7675:Cacna1s	UTSW	1	136110874	missense	probably damaging	1.00
R7746:Cacna1s	UTSW	1	136069018	missense	probably damaging	0.99
R7779:Cacna1s	UTSW	1	136119029	missense	probably damaging	1.00
R7850:Cacna1s	UTSW	1	136071048	missense	probably damaging	1.00
R7932:Cacna1s	UTSW	1	136084359	missense	probably damaging	0.99
R7935:Cacna1s	UTSW	1	136092595	missense	possibly damaging	0.62
R7950:Cacna1s	UTSW	1	136100625	missense	probably benign	0.01
R7969:Cacna1s	UTSW	1	136076732	missense	probably damaging	1.00
R8083:Cacna1s	UTSW	1	136095791	missense	possibly damaging	0.91
R8101:Cacna1s	UTSW	1	136118665	missense	probably benign	0.02
R8123:Cacna1s	UTSW	1	136108179	missense	probably damaging	1.00
R8191:Cacna1s	UTSW	1	136108155	missense	probably damaging	1.00
R8194:Cacna1s	UTSW	1	136077692	missense	probably benign	0.33
R8265:Cacna1s	UTSW	1	136092626	nonsense	probably null
R8301:Cacna1s	UTSW	1	136073441	unclassified	probably benign
R8310:Cacna1s	UTSW	1	136087337	missense	probably damaging	1.00
R8359:Cacna1s	UTSW	1	136116061	missense	probably benign	0.21
R8461:Cacna1s	UTSW	1	136073702	missense	possibly damaging	0.53
R8553:Cacna1s	UTSW	1	136091802	missense	possibly damaging	0.93
R8743:Cacna1s	UTSW	1	136105548	missense	probably damaging	1.00
R8766:Cacna1s	UTSW	1	136075143	missense	probably damaging	1.00
R8884:Cacna1s	UTSW	1	136115243	missense	probably benign	0.05
R8897:Cacna1s	UTSW	1	136117654	missense	probably benign	0.01
R8939:Cacna1s	UTSW	1	136086806	critical splice donor site	probably null
R8953:Cacna1s	UTSW	1	136097432	missense	possibly damaging	0.94
R9039:Cacna1s	UTSW	1	136088319	missense	probably benign
R9058:Cacna1s	UTSW	1	136070698	nonsense	probably null
R9137:Cacna1s	UTSW	1	136069006	missense	possibly damaging	0.89
R9332:Cacna1s	UTSW	1	136092714	nonsense	probably null
R9416:Cacna1s	UTSW	1	136094951	missense	possibly damaging	0.88
R9427:Cacna1s	UTSW	1	136084352	missense	probably benign	0.30
R9446:Cacna1s	UTSW	1	136117624	missense	probably benign	0.00
R9564:Cacna1s	UTSW	1	136118778	missense	probably benign
R9620:Cacna1s	UTSW	1	136108171	missense	probably damaging	1.00
X0025:Cacna1s	UTSW	1	136115970	missense	probably benign	0.00
Z1176:Cacna1s	UTSW	1	136107084	nonsense	probably null
Z1177:Cacna1s	UTSW	1	136117686	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- TGTAGCTCACTGAAAGAGGAGC -3'
(R):5'- CCTAGGTGAAAGAATTGTTGTTGC -3'

Sequencing Primer
(F):5'- CTCACTGAAAGAGGAGCAAGGAG -3'
(R):5'- ACACCATCAGCCTGGGAG -3'

Posted On

2020-07-28