Mutagenetix > Incidental Mutations

Incidental Mutation 'R2424:Cacna1d'

249507

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

040386-MU

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.648) question?

Stock #

R2424 (G1)

Quality Score

176

Status

Validated

Chromosome

Chromosomal Location

30039939-30491455 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 30049023 bp

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Asparagine at position 1828 (Y1828N)

Ref Sequence

ENSEMBL: ENSMUSP00000107868 (fasta)

Gene Model

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000112249
AA Change: Y1828N

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000107868
Gene: ENSMUSG00000015968
AA Change: Y1828N

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: Y1850N

PolyPhen 2 Score 0.921 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000107869
Gene: ENSMUSG00000015968
AA Change: Y1850N

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

noncoding transcript
Transcript: ENSMUST00000223573

Predicted Effect

possibly damaging
Transcript: ENSMUST00000223803
AA Change: Y1828N

PolyPhen 2 Score 0.869 (Sensitivity: 0.83; Specificity: 0.93)

Predicted Effect

possibly damaging
Transcript: ENSMUST00000224198
AA Change: Y1863N

PolyPhen 2 Score 0.807 (Sensitivity: 0.84; Specificity: 0.93)

Predicted Effect

probably benign
Transcript: ENSMUST00000224395

Predicted Effect

possibly damaging
Transcript: ENSMUST00000224785
AA Change: Y1819N

PolyPhen 2 Score 0.810 (Sensitivity: 0.84; Specificity: 0.93)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000225353

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000225717

Meta Mutation Damage Score

0.198

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.1%
20x: 94.3%

Validation Efficiency

100% (64/64)

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: 65 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921501E09Rik	T	C	17: 33,065,756	T691A	probably benign	Het
Aacs	A	G	5: 125,513,095		probably null	Het
Acot3	G	T	12: 84,053,864	R138L	probably damaging	Het
Ago3	A	G	4: 126,404,247	V160A	probably damaging	Het
Akap9	A	C	5: 4,065,279	E166D	probably damaging	Het
Arid5a	T	C	1: 36,318,501	Y136H	probably damaging	Het
Ascc3	T	C	10: 50,618,201	V244A	probably benign	Het
Atp10a	A	T	7: 58,794,555	H560L	probably benign	Het
Btbd6	A	G	12: 112,978,360	T482A	probably benign	Het
Capzb	A	G	4: 139,194,130	M1V	probably null	Het
Cdh9	T	G	15: 16,850,354	F524L	probably damaging	Het
Ctnna1	T	C	18: 35,253,707	S846P	probably benign	Het
Dab1	C	T	4: 104,731,751	A524V	probably benign	Het
Dock7	T	A	4: 98,945,307	R1886*	probably null	Het
Dpp3	A	T	19: 4,907,707	L711*	probably null	Het
Dst	T	A	1: 34,167,060	I566N	probably damaging	Het
Eif2b3	T	A	4: 117,070,848	S421R	probably benign	Het
Epg5	T	C	18: 77,968,613	V825A	probably benign	Het
Eya1	T	A	1: 14,270,848		probably benign	Het
Fam187a	T	C	11: 102,885,954	Y195H	probably damaging	Het
Fbn2	C	T	18: 58,203,787	C132Y	probably damaging	Het
Fbxw21	A	T	9: 109,157,519	Y97*	probably null	Het
Grin1	A	T	2: 25,318,652	C79S	probably null	Het
Haao	T	A	17: 83,835,562	Y118F	probably damaging	Het
Il11ra1	T	A	4: 41,768,222	S378T	probably damaging	Het
Kcnj5	A	T	9: 32,322,820	N66K	probably damaging	Het
Kif21a	T	A	15: 90,971,196	N668I	probably damaging	Het
Kprp	A	T	3: 92,825,605	L46Q	probably damaging	Het
Lama1	C	T	17: 67,798,665	T2056I	probably benign	Het
Madd	G	C	2: 91,166,622	D824E	probably damaging	Het
Mapk9	A	G	11: 49,863,672	N84S	probably damaging	Het
Mrpl39	A	G	16: 84,730,860	V160A	probably benign	Het
Mrpl9	T	C	3: 94,443,806	S98P	probably benign	Het
Mybpc3	A	T	2: 91,135,793	M1233L	probably benign	Het
Neb	A	G	2: 52,209,659		probably benign	Het
Ngly1	A	G	14: 16,290,721		probably null	Het
Nt5c1b	A	T	12: 10,370,072	T4S	probably damaging	Het
Obscn	T	C	11: 58,994,451		probably benign	Het
Olfr725	T	C	14: 50,034,824	Y193C	probably damaging	Het
Olfr904	T	C	9: 38,464,832	S264P	probably damaging	Het
Olfr92	T	C	17: 37,111,516	I155M	probably benign	Het
Olfr968	A	G	9: 39,772,297	F168L	probably benign	Het
Otog	A	T	7: 46,298,169	K64*	probably null	Het
Papola	A	G	12: 105,827,052	T544A	probably benign	Het
Phc1	A	G	6: 122,320,043	V790A	probably damaging	Het
Phf3	G	T	1: 30,806,349	R1252S	probably damaging	Het
Plxna2	C	T	1: 194,749,317	S538F	probably damaging	Het
Rgs17	T	A	10: 5,833,111	I159F	probably damaging	Het
Rgs17	T	A	10: 5,842,560	E62V	probably benign	Het
Rnase1	A	G	14: 51,145,547	Y117H	possibly damaging	Het
Rnf214	T	C	9: 45,899,798	D189G	probably damaging	Het
Sema4b	A	G	7: 80,219,275	N365S	probably damaging	Het
Setd2	A	G	9: 110,617,522	H2480R	probably benign	Het
Slc27a6	G	T	18: 58,605,117	C415F	probably benign	Het
Stim1	A	G	7: 102,408,405	I142V	probably benign	Het
Supt5	T	C	7: 28,315,165	I1070V	possibly damaging	Het
Tbp	T	C	17: 15,513,533	F174L	possibly damaging	Het
Tex26	A	G	5: 149,470,448		probably benign	Het
Tmem132d	A	G	5: 127,864,599	V479A	probably benign	Het
Ttn	T	C	2: 76,881,145		probably benign	Het
Urb2	T	A	8: 124,030,426	N957K	probably benign	Het
Usp24	T	C	4: 106,399,113		probably null	Het
Vmn2r114	T	C	17: 23,296,868	T550A	possibly damaging	Het
Vmn2r72	A	G	7: 85,750,953	V296A	probably damaging	Het
Vmn2r91	C	A	17: 18,136,169	Y699*	probably null	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
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

Predicted Primers

PCR Primer
(F):5'- AACTCCTGCCCTGATGTGTC -3'
(R):5'- TGAGTAGTCTTATGGCCCCG -3'

Sequencing Primer
(F):5'- ATGTGTCAGAGGAATCCTGAGTG -3'
(R):5'- GCACTCTGAGGGAGGACAC -3'

Posted On

2014-11-12