Mutagenetix > Incidental Mutation

Incidental Mutation 'R1646:Cacnb4'

173859

Institutional Source

Beutler Lab

Gene Symbol

Cacnb4

Ensembl Gene

ENSMUSG00000017412

Gene Name

calcium channel, voltage-dependent, beta 4 subunit

Synonyms

Cchb4, 3110038O15Rik

MMRRC Submission

039682-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.212) question?

Stock #

R1646 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

52318332-52566816 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 52364912 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 117 (I117T)

Ref Sequence

ENSEMBL: ENSMUSP00000077438 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000078324] [ENSMUST00000102760] [ENSMUST00000102761] [ENSMUST00000178799]

AlphaFold

Q8R0S4

PDB Structure

BETA4 SUBUNIT OF CA2+ CHANNEL [X-RAY DIFFRACTION]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000078324
AA Change: I117T

PolyPhen 2 Score 0.874 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000077438
Gene: ENSMUSG00000017412
AA Change: I117T

Domain	Start	End	E-Value	Type
Pfam:VGCC_beta4Aa_N	49	90	5.4e-27	PFAM
SH3	94	159	4.96e-2	SMART
low complexity region	172	189	N/A	INTRINSIC
low complexity region	193	206	N/A	INTRINSIC
GuKc	217	398	3.46e-37	SMART
low complexity region	465	481	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000102760
AA Change: I84T

PolyPhen 2 Score 0.674 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000099821
Gene: ENSMUSG00000017412
AA Change: I84T

Domain	Start	End	E-Value	Type
Pfam:VGCC_beta4Aa_N	16	57	9.4e-28	PFAM
SH3	61	126	4.96e-2	SMART
low complexity region	139	156	N/A	INTRINSIC
low complexity region	160	173	N/A	INTRINSIC
GuKc	184	365	3.46e-37	SMART
low complexity region	432	448	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000102761
AA Change: I71T

PolyPhen 2 Score 0.674 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000099822
Gene: ENSMUSG00000017412
AA Change: I71T

Domain	Start	End	E-Value	Type
Pfam:VGCC_beta4Aa_N	3	44	4.8e-27	PFAM
SH3	48	113	4.96e-2	SMART
low complexity region	126	143	N/A	INTRINSIC
low complexity region	147	160	N/A	INTRINSIC
GuKc	171	352	3.46e-37	SMART
low complexity region	419	435	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000178799
AA Change: I117T

PolyPhen 2 Score 0.539 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000136811
Gene: ENSMUSG00000017412
AA Change: I117T

Domain	Start	End	E-Value	Type
Pfam:VGCC_beta4Aa_N	49	90	1.3e-24	PFAM
SH3	94	159	4.96e-2	SMART
low complexity region	172	189	N/A	INTRINSIC
GuKc	217	398	3.46e-37	SMART
low complexity region	465	481	N/A	INTRINSIC

Meta Mutation Damage Score

0.5665

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.1%
20x: 91.8%

Validation Efficiency

96% (69/72)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the beta subunit family of voltage-dependent calcium channel complex proteins. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. The protein encoded by this locus plays an important role in calcium channel function by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Certain mutations in this gene have been associated with idiopathic generalized epilepsy (IGE), juvenile myoclonic epilepsy (JME), and episodic ataxia, type 5. [provided by RefSeq, Aug 2016]
PHENOTYPE: Homozygous mutants have lethargic behavior, unstable gait and seizures, with peripheral motor nerves showing reduced conduction velocity and prolonged distal latency. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Akna	T	G	4: 63,302,129 (GRCm39)	I581L	probably benign	Het
Capn1	A	T	19: 6,047,760 (GRCm39)	F434L	probably benign	Het
Cbs	T	C	17: 31,832,169 (GRCm39)	T547A	probably benign	Het
Col6a5	A	T	9: 105,739,948 (GRCm39)	L2557*	probably null	Het
Dach1	A	G	14: 98,406,550 (GRCm39)	S66P	unknown	Het
Ddx31	T	C	2: 28,782,532 (GRCm39)	V625A	probably benign	Het
Dmxl1	T	G	18: 50,095,328 (GRCm39)	V2969G	probably damaging	Het
Eapp	T	A	12: 54,732,745 (GRCm39)	K122*	probably null	Het
Elapor1	A	T	3: 108,370,306 (GRCm39)	S751T	probably damaging	Het
Epb41l5	G	T	1: 119,477,752 (GRCm39)		probably benign	Het
Fat1	T	C	8: 45,471,079 (GRCm39)	S1628P	probably damaging	Het
Fgfr2	T	A	7: 129,844,374 (GRCm39)	E37V	probably damaging	Het
Fgfr4	A	T	13: 55,313,777 (GRCm39)	N529Y	probably damaging	Het
Fsip2	A	T	2: 82,808,861 (GRCm39)	T1727S	probably benign	Het
Gak	A	T	5: 108,750,720 (GRCm39)	S397T	probably damaging	Het
Gm6040	T	A	8: 21,407,113 (GRCm39)	I36F	possibly damaging	Het
Grhl1	A	G	12: 24,661,860 (GRCm39)	D513G	possibly damaging	Het
Gstt1	T	A	10: 75,619,940 (GRCm39)	D219V	possibly damaging	Het
Hcfc2	T	G	10: 82,536,861 (GRCm39)	V91G	probably damaging	Het
Hells	A	T	19: 38,956,227 (GRCm39)	I808L	probably benign	Het
Icmt	T	A	4: 152,384,172 (GRCm39)	V110E	possibly damaging	Het
Ilrun	A	G	17: 28,012,934 (GRCm39)	S88P	probably damaging	Het
Iqca1	C	T	1: 90,067,760 (GRCm39)	V164M	probably damaging	Het
Klri1	G	A	6: 129,680,299 (GRCm39)	P119S	probably benign	Het
Krt71	C	A	15: 101,647,199 (GRCm39)		probably null	Het
Lpin1	A	G	12: 16,623,659 (GRCm39)		probably null	Het
Macir	A	T	1: 97,573,531 (GRCm39)	I178N	probably damaging	Het
Metap2	T	C	10: 93,706,059 (GRCm39)	H241R	probably damaging	Het
Myh15	A	G	16: 49,015,931 (GRCm39)	Y1869C	probably damaging	Het
Myo1h	G	A	5: 114,455,693 (GRCm39)	G59E	possibly damaging	Het
Ncam2	T	G	16: 81,262,594 (GRCm39)		probably benign	Het
Npat	T	C	9: 53,466,434 (GRCm39)	V241A	probably benign	Het
Npbwr1	C	A	1: 5,987,473 (GRCm39)	V14L	probably benign	Het
Nup37	T	A	10: 88,014,096 (GRCm39)	V323E	possibly damaging	Het
Or11g27	A	T	14: 50,771,040 (GRCm39)	Q57L	probably benign	Het
Or5m9b	A	G	2: 85,905,960 (GRCm39)	N292S	probably damaging	Het
Or5p59	C	T	7: 107,702,798 (GRCm39)	T94I	probably benign	Het
Or7a35	C	A	10: 78,853,340 (GRCm39)	Y61*	probably null	Het
Pdlim4	A	T	11: 53,947,080 (GRCm39)	L132Q	possibly damaging	Het
Ptcd3	T	C	6: 71,875,379 (GRCm39)	D201G	probably benign	Het
Ptk7	A	T	17: 46,897,223 (GRCm39)	F370I	probably benign	Het
Pus7l	T	C	15: 94,431,517 (GRCm39)	N371D	probably benign	Het
Pzp	G	A	6: 128,480,518 (GRCm39)	A589V	probably benign	Het
Rasef	T	A	4: 73,652,786 (GRCm39)	R572W	probably damaging	Het
Reep5	T	C	18: 34,482,712 (GRCm39)	T166A	probably benign	Het
Rhov	A	G	2: 119,101,501 (GRCm39)	V35A	probably damaging	Het
Ripk4	C	T	16: 97,545,097 (GRCm39)	G517R	probably damaging	Het
Rnasel	A	G	1: 153,630,800 (GRCm39)	T439A	probably damaging	Het
Slamf9	A	G	1: 172,304,907 (GRCm39)	T174A	probably benign	Het
Slc12a9	A	G	5: 137,321,411 (GRCm39)	L414P	probably damaging	Het
Slf1	G	A	13: 77,214,767 (GRCm39)	R640*	probably null	Het
Slfn8	G	T	11: 82,907,712 (GRCm39)	P277Q	probably damaging	Het
Stpg2	T	A	3: 139,125,463 (GRCm39)		probably benign	Het
Tm9sf3	A	C	19: 41,211,618 (GRCm39)	N408K	possibly damaging	Het
Trio	A	G	15: 27,758,433 (GRCm39)	V2049A	possibly damaging	Het
Ttn	A	T	2: 76,645,077 (GRCm39)	I11180N	probably damaging	Het
Ush2a	T	C	1: 188,148,018 (GRCm39)	C982R	probably damaging	Het
Usp36	C	T	11: 118,164,392 (GRCm39)	V207M	probably damaging	Het
Uvrag	T	C	7: 98,767,431 (GRCm39)	T67A	probably damaging	Het
Vasp	G	A	7: 18,994,903 (GRCm39)		probably benign	Het
Vmn2r115	T	C	17: 23,578,513 (GRCm39)	F662S	probably damaging	Het
Vmn2r54	A	T	7: 12,366,434 (GRCm39)	C167S	probably damaging	Het
Vmn2r71	C	A	7: 85,270,476 (GRCm39)	N547K	probably damaging	Het
Wasf2	A	G	4: 132,903,902 (GRCm39)	I37V	probably benign	Het
Wwc2	T	C	8: 48,295,937 (GRCm39)	E1111G	unknown	Het
Zfp317	A	G	9: 19,558,608 (GRCm39)	Y274C	probably damaging	Het
Zhx3	T	C	2: 160,623,195 (GRCm39)	Y324C	probably damaging	Het
Zzef1	T	C	11: 72,754,862 (GRCm39)		probably null	Het

Other mutations in Cacnb4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00961:Cacnb4	APN	2	52,367,724 (GRCm39)	missense	possibly damaging	0.46
IGL01328:Cacnb4	APN	2	52,354,637 (GRCm39)	missense	probably damaging	1.00
IGL01801:Cacnb4	APN	2	52,324,723 (GRCm39)	missense	probably benign	0.15
IGL01992:Cacnb4	APN	2	52,355,682 (GRCm39)	missense	probably damaging	1.00
IGL03030:Cacnb4	APN	2	52,364,894 (GRCm39)	missense	probably damaging	1.00
R0789:Cacnb4	UTSW	2	52,341,895 (GRCm39)	missense	probably damaging	1.00
R1069:Cacnb4	UTSW	2	52,345,623 (GRCm39)	missense	probably damaging	1.00
R2050:Cacnb4	UTSW	2	52,359,598 (GRCm39)	missense	probably damaging	0.99
R3939:Cacnb4	UTSW	2	52,359,501 (GRCm39)	missense	probably damaging	1.00
R3941:Cacnb4	UTSW	2	52,359,501 (GRCm39)	missense	probably damaging	1.00
R4455:Cacnb4	UTSW	2	52,355,665 (GRCm39)	missense	probably damaging	1.00
R4497:Cacnb4	UTSW	2	52,367,783 (GRCm39)	missense	probably damaging	1.00
R4707:Cacnb4	UTSW	2	52,364,927 (GRCm39)	missense	probably benign	0.45
R4824:Cacnb4	UTSW	2	52,565,822 (GRCm39)	missense	probably benign	0.00
R4957:Cacnb4	UTSW	2	52,448,303 (GRCm39)	missense	probably damaging	0.99
R5913:Cacnb4	UTSW	2	52,324,796 (GRCm39)	intron	probably benign
R6372:Cacnb4	UTSW	2	52,324,679 (GRCm39)	missense	probably benign	0.00
R6945:Cacnb4	UTSW	2	52,364,966 (GRCm39)	missense	probably damaging	1.00
R7557:Cacnb4	UTSW	2	52,359,579 (GRCm39)	missense	probably damaging	1.00
R7821:Cacnb4	UTSW	2	52,324,520 (GRCm39)	missense	possibly damaging	0.91
R8015:Cacnb4	UTSW	2	52,354,655 (GRCm39)	missense	probably damaging	1.00
R8043:Cacnb4	UTSW	2	52,355,663 (GRCm39)	missense	probably damaging	1.00
R8181:Cacnb4	UTSW	2	52,364,997 (GRCm39)	missense	probably benign	0.00
R8376:Cacnb4	UTSW	2	52,354,665 (GRCm39)	nonsense	probably null
R8466:Cacnb4	UTSW	2	52,354,679 (GRCm39)	missense	probably damaging	1.00
R8765:Cacnb4	UTSW	2	52,327,001 (GRCm39)	missense	probably damaging	0.99
R9018:Cacnb4	UTSW	2	52,324,706 (GRCm39)	missense	probably benign	0.26
R9574:Cacnb4	UTSW	2	52,327,016 (GRCm39)	missense	probably damaging	1.00
R9624:Cacnb4	UTSW	2	52,364,942 (GRCm39)	missense	probably benign	0.09
R9778:Cacnb4	UTSW	2	52,359,615 (GRCm39)	missense	probably damaging	0.96
Z1176:Cacnb4	UTSW	2	52,565,824 (GRCm39)	critical splice acceptor site	probably null

Predicted Primers

PCR Primer
(F):5'- CCTGGATACTGCTGCTACCAAACTC -3'
(R):5'- TTGCCTGGAACCATCATTCATCCTG -3'

Sequencing Primer
(F):5'- cacacacacacacacacac -3'
(R):5'- TCTGTCTCCAGTCCAAACCT -3'

Posted On

2014-04-24