Mutagenetix > Incidental Mutations

Incidental Mutation 'R0033:Cacna1d'

64559

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

038327-MU

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.721) question?

Stock #

R0033 (G1)

Quality Score

137

Status

Validated

Chromosome

Chromosomal Location

30039939-30491455 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 30105489 bp

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Leucine at position 993 (Q993L)

Ref Sequence

ENSEMBL: ENSMUSP00000153250 (fasta)

Gene Model

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000112249
AA Change: Q973L

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000107868
Gene: ENSMUSG00000015968
AA Change: Q973L

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

possibly damaging
Transcript: ENSMUST00000112250
AA Change: Q995L

PolyPhen 2 Score 0.894 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000107869
Gene: ENSMUSG00000015968
AA Change: Q995L

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: ENSMUST00000223803
AA Change: Q973L

PolyPhen 2 Score 0.267 (Sensitivity: 0.91; Specificity: 0.88)

Predicted Effect

probably damaging
Transcript: ENSMUST00000224198
AA Change: Q993L

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

Predicted Effect

probably benign
Transcript: ENSMUST00000224395

Predicted Effect

probably damaging
Transcript: ENSMUST00000224785
AA Change: Q973L

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)

Predicted Effect

probably benign
Transcript: ENSMUST00000224912

Meta Mutation Damage Score

0.3795

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 96.9%
20x: 93.3%

Validation Efficiency

100% (81/81)

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: 57 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3110009E18Rik	T	C	1: 120,188,064	F110L	probably damaging	Het
Agr3	C	T	12: 35,928,330	T14M	possibly damaging	Het
Ankib1	A	C	5: 3,769,588	D110E	possibly damaging	Het
Auts2	G	C	5: 131,440,093	D571E	probably damaging	Het
Cdkn3	C	A	14: 46,768,872	Y141*	probably null	Het
Ceacam12	T	G	7: 18,069,460		probably benign	Het
Celf1	T	C	2: 91,001,453		probably benign	Het
Col6a3	A	G	1: 90,802,245	S1780P	probably damaging	Het
Csf3r	A	G	4: 126,031,884	T151A	probably benign	Het
Ctss	G	A	3: 95,545,577		probably benign	Het
D430042O09Rik	T	G	7: 125,761,827	V103G	possibly damaging	Het
Emilin2	G	T	17: 71,275,014	T239K	probably benign	Het
Erp44	T	C	4: 48,241,289		probably benign	Het
Fbxl4	T	C	4: 22,377,017	V151A	probably damaging	Het
Fer1l4	G	A	2: 156,024,106		probably benign	Het
Gm12794	A	T	4: 101,941,684	Y284F	probably benign	Het
Gm43302	T	C	5: 105,276,844	D310G	probably benign	Het
Gstk1	A	G	6: 42,246,803		probably benign	Het
Hapln1	A	T	13: 89,601,813	Q159L	probably benign	Het
Hibch	A	G	1: 52,905,451	K296R	probably null	Het
Kcnh4	C	T	11: 100,746,932	G633E	probably benign	Het
Kdm7a	A	T	6: 39,165,197	Y382*	probably null	Het
Kirrel3	A	G	9: 35,000,963	I208V	probably benign	Het
Klc4	A	T	17: 46,635,433	C489S	probably damaging	Het
Lrrc8a	G	T	2: 30,255,345	C57F	probably damaging	Het
Ltbp1	A	G	17: 75,276,509	N435D	possibly damaging	Het
Macc1	T	A	12: 119,446,341	N281K	probably benign	Het
Myo16	A	T	8: 10,370,955	Y265F	probably damaging	Het
Myoc	G	A	1: 162,648,441	G238E	probably damaging	Het
Nlrp12	A	C	7: 3,240,407	S492A	probably damaging	Het
Obscn	A	G	11: 58,994,746		probably benign	Het
Olfr1413	A	G	1: 92,573,260	T30A	probably benign	Het
Olfr486	G	T	7: 108,171,927	D272E	probably benign	Het
Oplah	T	A	15: 76,297,134	Q1202L	probably benign	Het
Ppargc1b	G	A	18: 61,307,694	R718W	probably damaging	Het
Pwwp2b	A	T	7: 139,254,928	D95V	possibly damaging	Het
Rnf225	T	C	7: 12,928,158	L88P	probably damaging	Het
Slc12a1	A	G	2: 125,214,009	D820G	probably benign	Het
Slc12a4	G	T	8: 105,947,479		probably benign	Het
Slx4	C	T	16: 3,988,000	A72T	probably benign	Het
Snrnp200	T	C	2: 127,238,063	I1920T	probably damaging	Het
Stap2	C	T	17: 55,999,976	V234M	probably damaging	Het
Sv2b	A	G	7: 75,117,741	F636L	probably benign	Het
Tdp1	C	T	12: 99,935,052	T531I	probably benign	Het
Thra	G	A	11: 98,764,352	V353I	probably benign	Het
Tm7sf2	A	G	19: 6,066,422		probably benign	Het
Tmx4	A	T	2: 134,600,998		probably null	Het
Tnfrsf12a	A	G	17: 23,676,145		probably null	Het
Trav6n-5	T	A	14: 53,104,911	M14K	probably benign	Het
Ttn	T	A	2: 76,742,280	I26090F	probably damaging	Het
Tut1	G	T	19: 8,962,759	R369L	probably benign	Het
Uba5	T	A	9: 104,054,148	T241S	probably benign	Het
Unc13d	T	C	11: 116,069,165	T597A	probably benign	Het
Vmn1r58	A	T	7: 5,410,388	I281K	probably damaging	Het
Vmn1r59	A	G	7: 5,454,434	V109A	probably benign	Het
Xdh	T	A	17: 73,907,632	M773L	probably benign	Het
Zfp64	A	T	2: 168,925,715	I659N	possibly 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
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
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

Predicted Primers

PCR Primer
(F):5'- AAACTGCCACCCTGAGAAAGGATG -3'
(R):5'- TGCCAAGAGTTTGGGAAGAGCC -3'

Sequencing Primer
(F):5'- CCTAGCAGTAGGCATAAGGaaaaag -3'
(R):5'- GAAGAGCCCAGGTTTTTGC -3'

Posted On

2013-08-06