Mutagenetix > Incidental Mutations

Incidental Mutation 'R2568:Cacna1d'

254655

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

040427-MU

Accession Numbers

Is this an essential gene?

Probably essential (E-score: 0.836) question?

Stock #

R2568 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

30039939-30491455 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 30082511 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 1335 (I1335T)

Ref Sequence

ENSEMBL: ENSMUSP00000153250 (fasta)

Gene Model

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

AlphaFold

Q99246

Predicted Effect

probably damaging
Transcript: ENSMUST00000112249
AA Change: I1300T

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000107868
Gene: ENSMUSG00000015968
AA Change: I1300T

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: I1322T

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000107869
Gene: ENSMUSG00000015968
AA Change: I1322T

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

possibly damaging
Transcript: ENSMUST00000223803
AA Change: I1300T

PolyPhen 2 Score 0.820 (Sensitivity: 0.84; Specificity: 0.93)

Predicted Effect

probably damaging
Transcript: ENSMUST00000224198
AA Change: I1335T

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

Predicted Effect

probably benign
Transcript: ENSMUST00000224395

Predicted Effect

possibly damaging
Transcript: ENSMUST00000224785
AA Change: I1300T

PolyPhen 2 Score 0.848 (Sensitivity: 0.83; Specificity: 0.93)

Predicted Effect

probably benign
Transcript: ENSMUST00000224912

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000225717

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.0%
20x: 94.1%

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: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410089E03Rik	T	C	15: 8,201,269	V1010A	possibly damaging	Het
4930563D23Rik	A	G	16: 92,321,319	L27P	probably damaging	Het
A730071L15Rik	A	T	11: 6,200,161		probably benign	Het
Abca13	A	T	11: 9,333,310	N3244I	probably benign	Het
Adgrf5	A	G	17: 43,437,671	T219A	probably damaging	Het
Adgrg5	A	T	8: 94,934,021	N92I	probably damaging	Het
Agt	A	C	8: 124,556,955	V475G	probably damaging	Het
Akap6	A	G	12: 52,887,278	K518E	possibly damaging	Het
Apoh	T	G	11: 108,404,871	D133E	probably benign	Het
Axdnd1	T	A	1: 156,392,749	M234L	possibly damaging	Het
Cdh15	G	A	8: 122,862,024	R279Q	probably damaging	Het
Cfap206	T	A	4: 34,711,566	K444*	probably null	Het
Clasp2	A	G	9: 113,878,764	I614M	probably benign	Het
Col6a4	A	T	9: 106,063,076	D1218E	possibly damaging	Het
Csmd3	CCTTTGCGCTT	CCTT	15: 47,741,236		probably null	Het
D130043K22Rik	C	T	13: 24,883,891	T870M	probably damaging	Het
Dagla	C	A	19: 10,248,152	A883S	probably benign	Het
Dhx30	A	G	9: 110,097,195	V87A	probably damaging	Het
Dtx1	C	A	5: 120,710,184	V44L	possibly damaging	Het
Ecm2	T	A	13: 49,530,129	S528T	possibly damaging	Het
Egfem1	A	T	3: 29,582,931	N172I	probably damaging	Het
Fam102b	T	A	3: 108,978,848	N356I	probably benign	Het
Fam13a	T	G	6: 58,935,609	R686S	probably damaging	Het
Fmo1	T	A	1: 162,836,259	I234L	probably benign	Het
Foxj2	C	T	6: 122,828,372	R68W	probably damaging	Het
Foxo6	A	T	4: 120,268,764	M278K	probably benign	Het
Fsip2	A	G	2: 82,990,431	S5503G	probably benign	Het
Gdf5	C	G	2: 155,942,090	R100G	probably benign	Het
Il1b	A	T	2: 129,367,322	D129E	probably damaging	Het
Klhl29	A	G	12: 5,091,350	S545P	probably damaging	Het
Krt83	G	T	15: 101,487,827	R296S	possibly damaging	Het
Llgl1	T	G	11: 60,708,812	S509R	probably damaging	Het
Lmod1	A	T	1: 135,363,964	K186*	probably null	Het
Lrpprc	C	T	17: 84,726,649	A973T	probably damaging	Het
Marco	T	C	1: 120,494,785	H49R	possibly damaging	Het
Mylk4	T	C	13: 32,722,018	N394S	probably null	Het
Myo5a	A	G	9: 75,123,040	Y147C	probably damaging	Het
Myo5a	T	C	9: 75,151,897	V469A	probably damaging	Het
Myot	A	G	18: 44,337,216	T87A	probably benign	Het
Nav2	A	G	7: 49,597,564	H2154R	probably damaging	Het
Nek10	A	G	14: 14,999,112	E1037G	possibly damaging	Het
Olfr181	A	G	16: 58,925,923	V216A	probably benign	Het
Olfr341	T	C	2: 36,479,974	D52G	probably damaging	Het
Olfr677	A	G	7: 105,056,671	T142A	probably benign	Het
Pitrm1	G	T	13: 6,575,092	V869F	probably benign	Het
Plekhm3	CCTGCTGCTGCTGCTGCTGCTGCTGC	CCTGCTGCTGCTGCTGCTGCTGC	1: 64,937,781		probably benign	Het
Prdx1	T	G	4: 116,693,800	I156S	probably benign	Het
Rbks	T	A	5: 31,665,752	T107S	probably damaging	Het
Ryr3	G	A	2: 112,675,874	R3468W	probably damaging	Het
Scn1a	C	T	2: 66,273,469	D1805N	probably damaging	Het
Sirpa	T	C	2: 129,615,648	V214A	probably benign	Het
Slc35c1	T	C	2: 92,458,880	N94D	probably benign	Het
Sorbs2	A	T	8: 45,795,370	K553*	probably null	Het
Tectb	C	G	19: 55,180,999		probably benign	Het
Thg1l	A	G	11: 45,951,565	V142A	probably benign	Het
Tiparp	T	A	3: 65,553,130	Y513*	probably null	Het
Tmc6	A	G	11: 117,772,820	V522A	probably benign	Het
Trim39	T	A	17: 36,269,164		probably benign	Het
Trrap	G	A	5: 144,843,369		probably null	Het
Tulp3	C	T	6: 128,327,638	V218I	probably benign	Het
Vmn1r38	T	A	6: 66,776,971	I54F	probably benign	Het
Vmn2r23	T	A	6: 123,742,188	Y833*	probably null	Het
Zfp810	A	T	9: 22,279,238	S125T	probably benign	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
R2291:Cacna1d	UTSW	14	30042342	missense	probably damaging	1.00
R2399:Cacna1d	UTSW	14	30052487	missense	probably benign	0.34
R2424:Cacna1d	UTSW	14	30049023	missense	probably damaging	0.96
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
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'- ATAATCTCTGCTGACTCAGTGGTC -3'
(R):5'- CTGAGCCCCTGTGTTGTTAG -3'

Sequencing Primer
(F):5'- TGACTCAGTGGTCAGACAGAG -3'
(R):5'- CCCCTGTGTTGTTAGCATGTG -3'

Posted On

2014-12-04