Mutagenetix > Incidental Mutation

Incidental Mutation 'R2291:Cacna1d'

244378

Institutional Source

Beutler Lab

Gene Symbol

Cacna1d

Ensembl Gene

ENSMUSG00000015968

Gene Name

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

Synonyms

C79217, Cchl1a2, Cav1.3alpha1, Cchl1a, Cacnl1a2, D-LTCC, 8430418G19Rik

MMRRC Submission

040290-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.846) question?

Stock #

R2291 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

30039939-30491455 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 30042342 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Serine at position 2078 (R2078S)

Ref Sequence

ENSEMBL: ENSMUSP00000107869 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000067620] [ENSMUST00000112249] [ENSMUST00000112250] [ENSMUST00000118917] [ENSMUST00000223803] [ENSMUST00000224198] [ENSMUST00000224395] [ENSMUST00000224785]

AlphaFold

Q99246

Predicted Effect

probably benign
Transcript: ENSMUST00000067620

SMART Domains

Protein: ENSMUSP00000065542
Gene: ENSMUSG00000015970

Domain	Start	End	E-Value	Type
Pfam:GMC_oxred_N	43	341	2.4e-98	PFAM
Pfam:Lycopene_cycl	45	110	8.4e-8	PFAM
Pfam:GMC_oxred_C	431	569	2.5e-43	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000112249
AA Change: R2056S

PolyPhen 2 Score 0.870 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000107868
Gene: ENSMUSG00000015968
AA Change: R2056S

Domain	Start	End	E-Value	Type
low complexity region	1	10	N/A	INTRINSIC
low complexity region	54	67	N/A	INTRINSIC
Pfam:Ion_trans	163	405	4.8e-59	PFAM
PDB:4DEY\|B	406	502	3e-38	PDB
low complexity region	503	517	N/A	INTRINSIC
Pfam:Ion_trans	557	751	5.5e-46	PFAM
low complexity region	766	781	N/A	INTRINSIC
low complexity region	819	840	N/A	INTRINSIC
Pfam:Ion_trans	921	1151	7.2e-51	PFAM
Pfam:Ion_trans	1239	1448	3.6e-67	PFAM
Pfam:PKD_channel	1285	1455	1.9e-9	PFAM
Blast:EFh	1469	1497	2e-9	BLAST
Ca_chan_IQ	1583	1617	5.05e-16	SMART
low complexity region	1649	1661	N/A	INTRINSIC
low complexity region	1722	1728	N/A	INTRINSIC
low complexity region	1830	1840	N/A	INTRINSIC
low complexity region	1885	1905	N/A	INTRINSIC
low complexity region	1921	1936	N/A	INTRINSIC
low complexity region	2122	2133	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000112250
AA Change: R2078S

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

SMART Domains

Protein: ENSMUSP00000107869
Gene: ENSMUSG00000015968
AA Change: R2078S

Domain	Start	End	E-Value	Type
low complexity region	76	89	N/A	INTRINSIC
Pfam:Ion_trans	147	439	5.6e-72	PFAM
low complexity region	473	482	N/A	INTRINSIC
low complexity region	525	539	N/A	INTRINSIC
Pfam:Ion_trans	544	784	2e-56	PFAM
low complexity region	788	803	N/A	INTRINSIC
low complexity region	841	862	N/A	INTRINSIC
Pfam:Ion_trans	907	1185	2.6e-63	PFAM
Pfam:Ion_trans	1226	1482	1.7e-70	PFAM
Pfam:PKD_channel	1306	1477	1.2e-9	PFAM
Pfam:GPHH	1484	1553	2.3e-38	PFAM
Ca_chan_IQ	1605	1639	5.05e-16	SMART
Pfam:CAC1F_C	1649	2165	1.1e-68	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000118917

SMART Domains

Protein: ENSMUSP00000112916
Gene: ENSMUSG00000015970

Domain	Start	End	E-Value	Type
Pfam:GMC_oxred_N	43	341	2.4e-98	PFAM
Pfam:Lycopene_cycl	44	109	1.9e-8	PFAM
Pfam:GMC_oxred_C	431	569	5.9e-42	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000223573

Predicted Effect

possibly damaging
Transcript: ENSMUST00000223803
AA Change: R2056S

PolyPhen 2 Score 0.785 (Sensitivity: 0.85; Specificity: 0.93)

Predicted Effect

possibly damaging
Transcript: ENSMUST00000224198
AA Change: R2091S

PolyPhen 2 Score 0.947 (Sensitivity: 0.79; Specificity: 0.95)

Predicted Effect

probably benign
Transcript: ENSMUST00000224395

Predicted Effect

probably damaging
Transcript: ENSMUST00000224785
AA Change: R2047S

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000225353

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000225717

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.4%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a pore-forming subunit of the L-type, voltage-activated calcium channel family. These channels have been found to play a role in heart and smooth muscle contraction and in the transmission of auditory information. Homozygous knockout mice for this gene exhibit deafness and heart defects. These channels have also been linked to mitochondrial oxidative stress in a mouse model of Parkinson's disease. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2014]
PHENOTYPE: Homozygotes for targeted mutations exhibit small size, hypoinsulinemia, glucose intolerance, decreased number and size of pancreatic islets, deafness with degeneration of hair cells, bradycardia, and arrhythmia. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700006A11Rik	A	T	3: 124,413,801	I247N	probably damaging	Het
Afdn	A	G	17: 13,888,891	K1559E	probably damaging	Het
Ankhd1	C	T	18: 36,644,333	T1523I	probably benign	Het
Apc	T	A	18: 34,312,491	N795K	probably benign	Het
Arhgap26	G	T	18: 39,357,698		probably benign	Het
Atm	C	T	9: 53,490,909		probably null	Het
Atp1a4	T	C	1: 172,244,906	N394D	probably damaging	Het
Brinp3	T	A	1: 146,901,074	S420T	possibly damaging	Het
Cacna1e	T	C	1: 154,403,683	D1720G	probably damaging	Het
Camk2a	T	A	18: 60,963,959	V38E	probably damaging	Het
Camk4	G	A	18: 33,107,943		probably null	Het
Ccr7	G	A	11: 99,145,335	R254C	probably damaging	Het
Celf5	C	T	10: 81,467,047	G267D	probably damaging	Het
Cfap65	G	A	1: 74,926,475	P459S	probably damaging	Het
Chd1l	T	C	3: 97,591,283	K267E	probably damaging	Het
Chl1	T	A	6: 103,715,393	Y331N	probably damaging	Het
Cltc	G	A	11: 86,733,622	T158I	probably benign	Het
Col16a1	T	A	4: 130,067,040	D430E	unknown	Het
Cspg4	T	C	9: 56,892,743	V1597A	probably damaging	Het
Cstf2t	T	A	19: 31,084,864	L600H	probably benign	Het
Cyp27b1	T	C	10: 127,048,294	V5A	possibly damaging	Het
Depdc5	C	A	5: 32,979,402	Q1339K	probably damaging	Het
Diaph3	G	T	14: 86,966,446	P592Q	probably damaging	Het
Epha8	T	C	4: 136,933,347	M687V	probably damaging	Het
Fhod1	T	A	8: 105,336,964		probably benign	Het
Gls2	C	A	10: 128,207,610	S73*	probably null	Het
Gm3604	T	A	13: 62,371,843	M33L	probably damaging	Het
Gpr39	A	G	1: 125,677,541	T69A	probably benign	Het
Hal	T	C	10: 93,503,536	F496L	probably damaging	Het
Hipk1	T	C	3: 103,761,610	E490G	probably damaging	Het
Ints7	T	G	1: 191,606,203		probably null	Het
Itpr3	A	G	17: 27,113,579	E1799G	possibly damaging	Het
Kif11	T	A	19: 37,407,003	M570K	probably benign	Het
Kif18b	G	T	11: 102,908,270	Q702K	probably damaging	Het
Kif19a	A	G	11: 114,790,193	T247A	probably damaging	Het
Lama3	A	G	18: 12,525,079	E360G	probably damaging	Het
Loxl3	G	T	6: 83,037,488	A126S	probably benign	Het
Mc5r	C	T	18: 68,339,364	R265W	probably damaging	Het
Mpl	A	G	4: 118,449,000	V340A	probably benign	Het
Mrpl13	G	T	15: 55,548,219	H56Q	probably damaging	Het
Msr1	T	C	8: 39,624,222	T116A	probably benign	Het
N4bp3	T	C	11: 51,646,103	K48E	probably damaging	Het
Naaladl1	A	G	19: 6,106,195	T104A	probably benign	Het
Neu1	C	T	17: 34,932,766	R179W	probably damaging	Het
Olfr1053	A	T	2: 86,315,180	Y35*	probably null	Het
Olfr975	T	C	9: 39,950,334	T146A	probably benign	Het
Osbp	G	T	19: 11,973,834	E248*	probably null	Het
Otx1	T	A	11: 21,996,634		probably benign	Het
Parp4	A	T	14: 56,613,817	Q759L	probably damaging	Het
Pax6	A	C	2: 105,685,883	S169R	probably benign	Het
Pigg	T	G	5: 108,332,917	I389M	probably damaging	Het
Pla2g4a	C	A	1: 149,901,189	V59F	probably damaging	Het
Plcb4	A	T	2: 135,939,983	Q241H	probably benign	Het
Plpp6	A	G	19: 28,964,320	D107G	probably damaging	Het
Ppp6r2	T	A	15: 89,275,487	L459Q	probably damaging	Het
Prss55	A	T	14: 64,075,722	W238R	probably damaging	Het
Rgl1	C	T	1: 152,536,281	E446K	probably damaging	Het
Ric3	C	T	7: 109,038,883	G221D	probably damaging	Het
Rnf167	T	C	11: 70,649,303	F83S	probably damaging	Het
Ryr1	C	T	7: 29,098,777	V947M	probably damaging	Het
Scn1a	A	G	2: 66,288,968	L1397P	probably benign	Het
Sh3bp1	T	A	15: 78,918,319	V251E	possibly damaging	Het
Slc25a10	A	T	11: 120,497,074	I198L	probably benign	Het
Smoc2	A	T	17: 14,368,971	N234I	possibly damaging	Het
Spdl1	T	A	11: 34,819,309	K382*	probably null	Het
Ssrp1	G	A	2: 85,042,316		probably null	Het
Tril	G	T	6: 53,818,027	R737S	probably damaging	Het
Triqk	T	A	4: 12,974,817		probably null	Het
Ttc19	T	C	11: 62,283,693	Y128H	probably damaging	Het
Vmn1r15	T	C	6: 57,258,692	S182P	possibly damaging	Het
Vmn1r226	A	G	17: 20,688,213	I236V	probably damaging	Het
Vmn2r120	A	C	17: 57,509,479	N625K	probably damaging	Het
Vmn2r78	T	C	7: 86,920,154	I85T	probably damaging	Het
Wdr60	A	T	12: 116,229,571		probably null	Het
Whamm	C	T	7: 81,591,771	R277*	probably null	Het
Wnt7a	C	T	6: 91,394,486	V165I	probably benign	Het
Zbtb40	A	T	4: 136,985,017	Y1127N	possibly damaging	Het
Zfyve1	A	T	12: 83,547,931	H762Q	probably damaging	Het

Other mutations in Cacna1d

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00494:Cacna1d	APN	14	30096950	missense	probably damaging	0.97
IGL00857:Cacna1d	APN	14	30350681	missense	possibly damaging	0.83
IGL01015:Cacna1d	APN	14	30051742	splice site	probably benign
IGL01420:Cacna1d	APN	14	30051638	missense	probably benign	0.01
IGL01470:Cacna1d	APN	14	30099142	missense	probably damaging	0.99
IGL01560:Cacna1d	APN	14	30099206	missense	probably benign	0.00
IGL01617:Cacna1d	APN	14	30102371	missense	probably damaging	1.00
IGL01820:Cacna1d	APN	14	30042866	missense	possibly damaging	0.79
IGL01948:Cacna1d	APN	14	30124794	missense	probably damaging	1.00
IGL02702:Cacna1d	APN	14	30123533	nonsense	probably null
IGL02864:Cacna1d	APN	14	30051706	missense	probably benign	0.10
IGL03082:Cacna1d	APN	14	30099233	missense	probably damaging	1.00
Brisk	UTSW	14	30171314	missense	possibly damaging	0.91
Troppo	UTSW	14	30123454	missense	probably damaging	1.00
PIT4651001:Cacna1d	UTSW	14	30178645	missense	probably damaging	1.00
R0015:Cacna1d	UTSW	14	30114971	missense	probably benign	0.00
R0015:Cacna1d	UTSW	14	30114971	missense	probably benign	0.00
R0033:Cacna1d	UTSW	14	30105489	missense	probably damaging	0.99
R0047:Cacna1d	UTSW	14	30346790	splice site	probably benign
R0047:Cacna1d	UTSW	14	30346790	splice site	probably benign
R0051:Cacna1d	UTSW	14	30111095	missense	probably damaging	1.00
R0051:Cacna1d	UTSW	14	30111095	missense	probably damaging	1.00
R0067:Cacna1d	UTSW	14	30075010	unclassified	probably benign
R0067:Cacna1d	UTSW	14	30075010	unclassified	probably benign
R0238:Cacna1d	UTSW	14	30123496	missense	probably benign	0.29
R0238:Cacna1d	UTSW	14	30123496	missense	probably benign	0.29
R0239:Cacna1d	UTSW	14	30123496	missense	probably benign	0.29
R0239:Cacna1d	UTSW	14	30123496	missense	probably benign	0.29
R0240:Cacna1d	UTSW	14	30096969	missense	probably benign	0.00
R0240:Cacna1d	UTSW	14	30096969	missense	probably benign	0.00
R0284:Cacna1d	UTSW	14	30072105	missense	probably damaging	1.00
R0416:Cacna1d	UTSW	14	30100688	splice site	probably benign
R0427:Cacna1d	UTSW	14	30346817	missense	probably damaging	0.99
R0517:Cacna1d	UTSW	14	30179275	missense	probably damaging	1.00
R0639:Cacna1d	UTSW	14	30171294	critical splice donor site	probably null
R0727:Cacna1d	UTSW	14	30130115	critical splice donor site	probably null
R0732:Cacna1d	UTSW	14	30042920	missense	probably damaging	0.99
R0843:Cacna1d	UTSW	14	30124871	missense	probably damaging	1.00
R0900:Cacna1d	UTSW	14	30111082	missense	probably damaging	1.00
R1278:Cacna1d	UTSW	14	30178703	missense	probably damaging	1.00
R1340:Cacna1d	UTSW	14	30072067	missense	probably damaging	0.96
R1527:Cacna1d	UTSW	14	30107796	missense	probably damaging	1.00
R1711:Cacna1d	UTSW	14	30066056	missense	probably damaging	1.00
R1736:Cacna1d	UTSW	14	30089863	missense	probably damaging	1.00
R1763:Cacna1d	UTSW	14	30099196	missense	probably benign	0.25
R2034:Cacna1d	UTSW	14	30089863	missense	probably damaging	1.00
R2086:Cacna1d	UTSW	14	30047357	missense	possibly damaging	0.83
R2126:Cacna1d	UTSW	14	30123163	missense	probably damaging	1.00
R2218:Cacna1d	UTSW	14	30123091	missense	probably damaging	1.00
R2219:Cacna1d	UTSW	14	30042090	missense	probably damaging	1.00
R2262:Cacna1d	UTSW	14	30491016	missense	possibly damaging	0.46
R2399:Cacna1d	UTSW	14	30052487	missense	probably benign	0.34
R2424:Cacna1d	UTSW	14	30049023	missense	probably damaging	0.96
R2568:Cacna1d	UTSW	14	30082511	missense	probably damaging	0.99
R4038:Cacna1d	UTSW	14	30066083	missense	probably damaging	0.96
R4509:Cacna1d	UTSW	14	30096971	missense	probably damaging	1.00
R4649:Cacna1d	UTSW	14	30095408	missense	probably benign
R4650:Cacna1d	UTSW	14	30095408	missense	probably benign
R4652:Cacna1d	UTSW	14	30095408	missense	probably benign
R5009:Cacna1d	UTSW	14	30079332	missense	probably damaging	1.00
R5058:Cacna1d	UTSW	14	30114244	nonsense	probably null
R5063:Cacna1d	UTSW	14	30051383	missense	probably benign
R5138:Cacna1d	UTSW	14	30490972	missense	probably benign
R5151:Cacna1d	UTSW	14	30123323	missense	probably damaging	1.00
R5278:Cacna1d	UTSW	14	30352924	critical splice donor site	probably null
R5286:Cacna1d	UTSW	14	30350725	missense	possibly damaging	0.69
R5313:Cacna1d	UTSW	14	30346841	missense	probably benign	0.38
R5383:Cacna1d	UTSW	14	30045279	missense	possibly damaging	0.51
R5387:Cacna1d	UTSW	14	30100751	missense	probably damaging	1.00
R5514:Cacna1d	UTSW	14	30350833	nonsense	probably null
R5524:Cacna1d	UTSW	14	30042129	missense	probably benign	0.01
R5663:Cacna1d	UTSW	14	30123340	missense	probably damaging	1.00
R5712:Cacna1d	UTSW	14	30074997	missense	probably damaging	1.00
R5796:Cacna1d	UTSW	14	30066116	missense	probably damaging	1.00
R5906:Cacna1d	UTSW	14	30096960	missense	probably damaging	1.00
R5923:Cacna1d	UTSW	14	30111148	missense	probably damaging	1.00
R5936:Cacna1d	UTSW	14	30171314	missense	possibly damaging	0.91
R5938:Cacna1d	UTSW	14	30103735	missense	probably damaging	1.00
R6041:Cacna1d	UTSW	14	30042357	missense	probably damaging	1.00
R6432:Cacna1d	UTSW	14	30123454	missense	probably damaging	1.00
R6486:Cacna1d	UTSW	14	30114233	missense	probably benign	0.01
R6600:Cacna1d	UTSW	14	30114235	missense	probably benign	0.15
R6661:Cacna1d	UTSW	14	30089875	missense	probably damaging	1.00
R6753:Cacna1d	UTSW	14	30042786	missense	probably damaging	1.00
R6804:Cacna1d	UTSW	14	30051665	missense	probably benign	0.00
R6851:Cacna1d	UTSW	14	30042782	missense	probably damaging	1.00
R6863:Cacna1d	UTSW	14	30075852	missense	probably damaging	1.00
R6916:Cacna1d	UTSW	14	30095364	missense	probably damaging	1.00
R6925:Cacna1d	UTSW	14	30051637	missense	probably benign
R7066:Cacna1d	UTSW	14	30352978	intron	probably benign
R7188:Cacna1d	UTSW	14	30089833	missense	probably benign
R7242:Cacna1d	UTSW	14	30178706	missense	probably benign	0.00
R7249:Cacna1d	UTSW	14	30142703	missense	probably damaging	1.00
R7250:Cacna1d	UTSW	14	30075151	missense	probably damaging	1.00
R7274:Cacna1d	UTSW	14	30142643	missense	probably damaging	1.00
R7336:Cacna1d	UTSW	14	30045282	missense	probably benign	0.18
R7343:Cacna1d	UTSW	14	30123057	missense	probably benign	0.02
R7411:Cacna1d	UTSW	14	30352990	start codon destroyed	probably null
R7461:Cacna1d	UTSW	14	30066163	missense	probably benign	0.05
R7534:Cacna1d	UTSW	14	30079362	missense	probably damaging	1.00
R7613:Cacna1d	UTSW	14	30066163	missense	probably benign	0.05
R7661:Cacna1d	UTSW	14	30047220	missense	probably benign	0.07
R7754:Cacna1d	UTSW	14	30075852	missense	probably damaging	1.00
R7759:Cacna1d	UTSW	14	30099188	missense	probably benign	0.01
R7784:Cacna1d	UTSW	14	30123439	missense	probably damaging	1.00
R7808:Cacna1d	UTSW	14	30111069	missense	probably damaging	1.00
R7965:Cacna1d	UTSW	14	30047313	nonsense	probably null
R8225:Cacna1d	UTSW	14	30123033	missense	probably benign	0.23
R8259:Cacna1d	UTSW	14	30051518	missense	probably benign
R8348:Cacna1d	UTSW	14	30102407	missense	probably damaging	1.00
R8448:Cacna1d	UTSW	14	30102407	missense	probably damaging	1.00
R8822:Cacna1d	UTSW	14	30178735	missense	probably benign	0.02
R8848:Cacna1d	UTSW	14	30123326	missense	possibly damaging	0.89
R9122:Cacna1d	UTSW	14	30123445	missense	probably damaging	1.00
R9122:Cacna1d	UTSW	14	30130168	missense	probably benign	0.00
R9169:Cacna1d	UTSW	14	30074916	missense	probably damaging	1.00
R9199:Cacna1d	UTSW	14	30042936	missense	probably benign	0.26
R9203:Cacna1d	UTSW	14	30051712	missense	probably benign	0.04
R9263:Cacna1d	UTSW	14	30074968	missense	probably damaging	1.00
R9346:Cacna1d	UTSW	14	30096923	missense	possibly damaging	0.86
R9444:Cacna1d	UTSW	14	30107784	critical splice donor site	probably null
R9487:Cacna1d	UTSW	14	30123462	missense	possibly damaging	0.90
R9542:Cacna1d	UTSW	14	30123359	missense	probably benign	0.00
R9651:Cacna1d	UTSW	14	30042924	missense	probably benign	0.00
R9785:Cacna1d	UTSW	14	30102343	critical splice donor site	probably null
Z1176:Cacna1d	UTSW	14	30111116	missense	probably benign	0.15
Z1176:Cacna1d	UTSW	14	30179188	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- AATCATCTCATCTGCCAGGTC -3'
(R):5'- TTCGACACCAACAGAGCTGAG -3'

Sequencing Primer
(F):5'- AAAGTCCTGGAGCTCATAGTCCTG -3'
(R):5'- AGCTGAGCTCATTTATGGTTAGCATC -3'

Posted On

2014-10-30