Mutagenetix > Incidental Mutation

Incidental Mutation 'R0437:Clcn3'

39079

Institutional Source

Beutler Lab

Gene Symbol

Clcn3

Ensembl Gene

ENSMUSG00000004319

Gene Name

chloride channel, voltage-sensitive 3

Synonyms

Clc3

MMRRC Submission

038638-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.456) question?

Stock #

R0437 (G1)

Quality Score

217

Status

Validated

Chromosome

Chromosomal Location

61363423-61436334 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 61387571 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 199 (V199A)

Ref Sequence

ENSEMBL: ENSMUSP00000105931 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000004430] [ENSMUST00000056508] [ENSMUST00000093490] [ENSMUST00000110301] [ENSMUST00000110302]

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000004430
AA Change: V226A

PolyPhen 2 Score 0.688 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000004430
Gene: ENSMUSG00000004319
AA Change: V226A

Domain	Start	End	E-Value	Type
transmembrane domain	128	150	N/A	INTRINSIC
Pfam:Voltage_CLC	220	623	1.4e-111	PFAM
CBS	667	717	2.46e-1	SMART
CBS	758	805	2.08e-8	SMART
low complexity region	847	861	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000056508
AA Change: V199A

PolyPhen 2 Score 0.047 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000058648
Gene: ENSMUSG00000004319
AA Change: V199A

Domain	Start	End	E-Value	Type
transmembrane domain	101	123	N/A	INTRINSIC
Pfam:Voltage_CLC	193	596	1.4e-103	PFAM
CBS	640	690	2.46e-1	SMART
CBS	731	778	6.59e-11	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000093490
AA Change: V168A

PolyPhen 2 Score 0.123 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000091202
Gene: ENSMUSG00000004319
AA Change: V168A

Domain	Start	End	E-Value	Type
transmembrane domain	70	92	N/A	INTRINSIC
Pfam:Voltage_CLC	162	565	1.2e-103	PFAM
CBS	609	659	2.46e-1	SMART
CBS	700	747	6.59e-11	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000110301
AA Change: V226A

PolyPhen 2 Score 0.123 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000105930
Gene: ENSMUSG00000004319
AA Change: V226A

Domain	Start	End	E-Value	Type
transmembrane domain	128	150	N/A	INTRINSIC
Pfam:Voltage_CLC	220	623	2.7e-103	PFAM
CBS	667	717	2.46e-1	SMART
CBS	758	805	6.59e-11	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000110302
AA Change: V199A

PolyPhen 2 Score 0.688 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000105931
Gene: ENSMUSG00000004319
AA Change: V199A

Domain	Start	End	E-Value	Type
transmembrane domain	101	123	N/A	INTRINSIC
Pfam:Voltage_CLC	193	596	1.3e-103	PFAM
CBS	640	690	2.46e-1	SMART
CBS	731	778	2.08e-8	SMART
low complexity region	820	834	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129672

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000132234

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147824

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145493

Meta Mutation Damage Score

0.5223

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.0%
20x: 94.8%

Validation Efficiency

100% (104/104)

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 voltage-gated chloride channel (ClC) family. The encoded protein is present in all cell types and localized in plasma membranes and in intracellular vesicles. It is a multi-pass membrane protein which contains a ClC domain and two additional C-terminal CBS (cystathionine beta-synthase) domains. The ClC domain catalyzes the selective flow of Cl- ions across cell membranes, and the CBS domain may have a regulatory function. This protein plays a role in both acidification and transmitter loading of GABAergic synaptic vesicles, and in smooth muscle cell activation and neointima formation. This protein is required for lysophosphatidic acid (LPA)-activated Cl- current activity and fibroblast-to-myofibroblast differentiation. The protein activity is regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in glioma cells. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
PHENOTYPE: Nullizygous mutations cause degeneration of hippocampal neurons and retinal photoreceptors, reduced body weight, behavioral deficits, gliosis, kyphosis and premature death, and may alter male fertility, ileum morphology, liver physiology, seizure susceptibility, and behavioral response to drugs. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 99 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4833420G17Rik	G	A	13: 119,606,631 (GRCm39)	R291K	probably benign	Het
Abca2	T	C	2: 25,332,857 (GRCm39)	S1519P	probably damaging	Het
Abcb11	G	A	2: 69,087,639 (GRCm39)	A1042V	probably damaging	Het
Abcc10	A	T	17: 46,623,845 (GRCm39)		probably null	Het
Abcc10	G	T	17: 46,623,846 (GRCm39)		probably benign	Het
Alkbh3	A	C	2: 93,811,914 (GRCm39)	L240V	probably damaging	Het
Apol10b	T	C	15: 77,469,608 (GRCm39)	S190G	probably benign	Het
Atp1a3	C	A	7: 24,698,392 (GRCm39)	C135F	probably benign	Het
Atp4a	C	G	7: 30,419,526 (GRCm39)	R659G	probably benign	Het
Bicra	A	G	7: 15,722,687 (GRCm39)	S277P	possibly damaging	Het
Bltp1	A	T	3: 37,043,953 (GRCm39)	H2820L	possibly damaging	Het
Bmp8a	T	C	4: 123,210,690 (GRCm39)	E275G	probably benign	Het
Ccdc102a	T	C	8: 95,640,054 (GRCm39)	E80G	probably damaging	Het
Cdh23	T	C	10: 60,246,576 (GRCm39)	D954G	probably damaging	Het
Chrm4	A	G	2: 91,758,788 (GRCm39)	T399A	possibly damaging	Het
Crlf1	T	C	8: 70,952,164 (GRCm39)		probably null	Het
Crx	G	T	7: 15,605,071 (GRCm39)	S57*	probably null	Het
Cstpp1	A	G	2: 91,252,298 (GRCm39)	L21P	probably damaging	Het
Cyp4f16	A	G	17: 32,756,072 (GRCm39)	I34V	possibly damaging	Het
Daxx	T	C	17: 34,132,598 (GRCm39)	V576A	probably benign	Het
Ddx17	C	T	15: 79,421,672 (GRCm39)	R351H	probably damaging	Het
Dhx38	T	C	8: 110,285,261 (GRCm39)		probably benign	Het
Dnd1	T	C	18: 36,897,552 (GRCm39)		probably benign	Het
Dync1i2	A	T	2: 71,058,169 (GRCm39)		probably null	Het
E2f6	T	C	12: 16,866,446 (GRCm39)	S52P	probably benign	Het
Epb41l4a	A	G	18: 34,013,326 (GRCm39)	F116S	probably damaging	Het
Ext1	T	C	15: 52,969,502 (GRCm39)	N362S	probably damaging	Het
Fam227a	C	A	15: 79,528,189 (GRCm39)	K79N	possibly damaging	Het
Fam228a	T	A	12: 4,782,759 (GRCm39)	L111F	probably damaging	Het
Fat2	T	C	11: 55,173,625 (GRCm39)	T2363A	probably benign	Het
Fat3	A	T	9: 15,908,228 (GRCm39)	N2591K	probably damaging	Het
Frem2	A	G	3: 53,560,436 (GRCm39)	M1357T	possibly damaging	Het
Frmd4b	A	T	6: 97,400,424 (GRCm39)	V29D	probably damaging	Het
G930045G22Rik	A	G	6: 50,823,918 (GRCm39)		noncoding transcript	Het
Galnt3	A	G	2: 65,937,573 (GRCm39)	S46P	possibly damaging	Het
Gmeb2	A	G	2: 180,895,766 (GRCm39)	V468A	possibly damaging	Het
Herc2	C	T	7: 55,869,563 (GRCm39)	R4271*	probably null	Het
Il5	C	A	11: 53,614,733 (GRCm39)		probably benign	Het
Ints9	G	A	14: 65,223,818 (GRCm39)		probably benign	Het
Itga10	T	C	3: 96,556,453 (GRCm39)	F196S	probably damaging	Het
Itgb3bp	T	C	4: 99,670,126 (GRCm39)	T138A	probably damaging	Het
Kcnd1	G	A	X: 7,690,922 (GRCm39)	V281M	probably benign	Het
Lcp2	T	C	11: 34,037,229 (GRCm39)	L391P	probably benign	Het
Lrrc66	T	C	5: 73,765,030 (GRCm39)	Y671C	probably benign	Het
Mettl23	T	C	11: 116,740,120 (GRCm39)	V197A	possibly damaging	Het
Mmp15	C	A	8: 96,097,400 (GRCm39)	D456E	probably benign	Het
Mospd4	T	C	18: 46,598,848 (GRCm39)		noncoding transcript	Het
Mov10l1	C	A	15: 88,889,515 (GRCm39)	H484N	probably damaging	Het
Mphosph9	T	C	5: 124,453,631 (GRCm39)	Q197R	probably benign	Het
Ms4a1	T	A	19: 11,233,933 (GRCm39)		probably null	Het
Mybbp1a	T	C	11: 72,339,674 (GRCm39)	V919A	possibly damaging	Het
Mycbpap	A	T	11: 94,404,338 (GRCm39)		probably benign	Het
Naip6	G	A	13: 100,433,432 (GRCm39)	S1135F	possibly damaging	Het
Ndufc2	T	A	7: 97,049,544 (GRCm39)	M50K	probably benign	Het
Npr2	T	C	4: 43,648,082 (GRCm39)	V842A	probably damaging	Het
Ntsr2	G	T	12: 16,703,696 (GRCm39)	G66W	probably damaging	Het
Obscn	T	C	11: 58,885,914 (GRCm39)		probably benign	Het
Optn	C	T	2: 5,028,926 (GRCm39)	G526R	probably damaging	Het
Or4c11	T	A	2: 88,695,229 (GRCm39)	N93K	probably benign	Het
Or4c114	T	A	2: 88,904,956 (GRCm39)	I160F	probably benign	Het
Or6c33	T	C	10: 129,853,965 (GRCm39)	V245A	probably damaging	Het
Or6k14	G	A	1: 173,927,965 (GRCm39)	G314R	probably benign	Het
Otud4	T	A	8: 80,396,626 (GRCm39)	H628Q	probably benign	Het
Padi6	T	C	4: 140,456,240 (GRCm39)	T585A	probably benign	Het
Pex16	G	T	2: 92,205,937 (GRCm39)	R10L	probably damaging	Het
Pitpnm2	A	G	5: 124,269,152 (GRCm39)		probably benign	Het
Pom121l2	A	G	13: 22,167,375 (GRCm39)	T549A	possibly damaging	Het
Prdm15	A	T	16: 97,613,759 (GRCm39)	M470K	probably benign	Het
Prkag2	T	A	5: 25,233,503 (GRCm39)	D49V	possibly damaging	Het
Prl3c1	A	G	13: 27,383,447 (GRCm39)	M38V	probably benign	Het
Prpf18	T	A	2: 4,648,572 (GRCm39)	I85F	possibly damaging	Het
Psg27	A	G	7: 18,294,636 (GRCm39)		probably benign	Het
Relt	A	G	7: 100,497,991 (GRCm39)		probably benign	Het
Rskr	T	C	11: 78,182,362 (GRCm39)	L57P	probably benign	Het
Serpina3b	A	T	12: 104,096,929 (GRCm39)	N70I	probably damaging	Het
Slc19a3	T	C	1: 83,000,286 (GRCm39)	S244G	probably benign	Het
Slc39a5	T	C	10: 128,235,716 (GRCm39)	T81A	possibly damaging	Het
Slc7a2	G	A	8: 41,357,563 (GRCm39)	G277D	probably damaging	Het
Slc9c1	C	T	16: 45,420,250 (GRCm39)		probably benign	Het
Slx1b	A	G	7: 126,291,753 (GRCm39)	F104L	probably benign	Het
Smg6	G	A	11: 74,820,527 (GRCm39)	S266N	probably damaging	Het
Spata9	T	C	13: 76,146,614 (GRCm39)	V162A	possibly damaging	Het
Szrd1	T	C	4: 140,846,055 (GRCm39)	I47V	probably benign	Het
Tha1	G	T	11: 117,759,401 (GRCm39)	L363M	probably benign	Het
Tmc6	G	A	11: 117,669,087 (GRCm39)	T89I	possibly damaging	Het
Tmem132d	C	T	5: 127,866,849 (GRCm39)	G684R	probably damaging	Het
Trim55	G	A	3: 19,725,142 (GRCm39)	G220S	probably benign	Het
Ttn	A	G	2: 76,600,874 (GRCm39)	L18836P	probably damaging	Het
Ubn1	G	T	16: 4,890,048 (GRCm39)		probably benign	Het
Ush2a	T	G	1: 188,643,228 (GRCm39)	W4197G	probably benign	Het
Vmn1r189	A	T	13: 22,286,231 (GRCm39)	V202E	probably damaging	Het
Vmn1r209	T	C	13: 22,990,526 (GRCm39)	I55V	probably benign	Het
Vmn2r86	A	T	10: 130,282,412 (GRCm39)	C735S	probably damaging	Het
Vwf	A	T	6: 125,543,281 (GRCm39)	D174V	probably damaging	Het
Zfp438	T	C	18: 5,214,910 (GRCm39)	N16S	probably damaging	Het
Zfp444	C	T	7: 6,192,408 (GRCm39)	T142I	probably benign	Het
Zfp804a	A	G	2: 81,884,135 (GRCm39)	M1V	probably null	Het
Zfp936	T	G	7: 42,838,734 (GRCm39)	I67S	probably benign	Het
Zfp948	A	T	17: 21,807,260 (GRCm39)	N151Y	unknown	Het

Other mutations in Clcn3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00782:Clcn3	APN	8	61,375,826 (GRCm39)	missense	probably damaging	0.99
IGL01088:Clcn3	APN	8	61,390,381 (GRCm39)	missense	probably damaging	1.00
IGL01449:Clcn3	APN	8	61,387,632 (GRCm39)	missense	probably damaging	0.97
IGL01792:Clcn3	APN	8	61,382,356 (GRCm39)	missense	probably damaging	1.00
IGL01845:Clcn3	APN	8	61,366,129 (GRCm39)	missense	probably benign	0.08
IGL01984:Clcn3	APN	8	61,382,614 (GRCm39)	missense	probably damaging	1.00
IGL02041:Clcn3	APN	8	61,376,187 (GRCm39)	missense	probably damaging	0.99
IGL02199:Clcn3	APN	8	61,380,308 (GRCm39)	missense	possibly damaging	0.82
IGL02199:Clcn3	APN	8	61,386,126 (GRCm39)	nonsense	probably null
IGL02456:Clcn3	APN	8	61,394,391 (GRCm39)	missense	probably damaging	1.00
IGL03353:Clcn3	APN	8	61,376,022 (GRCm39)	missense	probably benign	0.37
Precipice	UTSW	8	61,394,433 (GRCm39)	missense	probably benign	0.16
R0003:Clcn3	UTSW	8	61,380,330 (GRCm39)	nonsense	probably null
R0023:Clcn3	UTSW	8	61,386,104 (GRCm39)	splice site	probably benign
R0023:Clcn3	UTSW	8	61,386,104 (GRCm39)	splice site	probably benign
R0349:Clcn3	UTSW	8	61,394,382 (GRCm39)	missense	possibly damaging	0.91
R0784:Clcn3	UTSW	8	61,382,237 (GRCm39)	missense	probably benign	0.25
R0840:Clcn3	UTSW	8	61,382,188 (GRCm39)	missense	probably benign	0.22
R1167:Clcn3	UTSW	8	61,375,822 (GRCm39)	critical splice donor site	probably null
R2035:Clcn3	UTSW	8	61,387,632 (GRCm39)	missense	probably damaging	0.97
R2193:Clcn3	UTSW	8	61,382,221 (GRCm39)	missense	possibly damaging	0.56
R3697:Clcn3	UTSW	8	61,366,157 (GRCm39)	missense	probably benign	0.02
R3736:Clcn3	UTSW	8	61,436,686 (GRCm39)	unclassified	probably benign
R4676:Clcn3	UTSW	8	61,383,685 (GRCm39)	intron	probably benign
R4807:Clcn3	UTSW	8	61,387,564 (GRCm39)	missense	probably damaging	1.00
R5112:Clcn3	UTSW	8	61,407,586 (GRCm39)	missense	probably benign	0.07
R5200:Clcn3	UTSW	8	61,376,039 (GRCm39)	missense	probably damaging	0.99
R5652:Clcn3	UTSW	8	61,372,387 (GRCm39)	missense	possibly damaging	0.81
R5712:Clcn3	UTSW	8	61,390,332 (GRCm39)	critical splice donor site	probably null
R5731:Clcn3	UTSW	8	61,375,923 (GRCm39)	missense	possibly damaging	0.46
R5814:Clcn3	UTSW	8	61,387,607 (GRCm39)	missense	probably damaging	1.00
R6134:Clcn3	UTSW	8	61,387,607 (GRCm39)	missense	probably damaging	1.00
R6370:Clcn3	UTSW	8	61,376,058 (GRCm39)	missense	probably damaging	1.00
R6371:Clcn3	UTSW	8	61,390,369 (GRCm39)	missense	probably benign	0.06
R6394:Clcn3	UTSW	8	61,394,325 (GRCm39)	missense	probably damaging	0.99
R6466:Clcn3	UTSW	8	61,382,595 (GRCm39)	missense	probably damaging	1.00
R6588:Clcn3	UTSW	8	61,367,861 (GRCm39)	missense	probably benign	0.03
R6750:Clcn3	UTSW	8	61,367,809 (GRCm39)	missense	possibly damaging	0.93
R7522:Clcn3	UTSW	8	61,394,446 (GRCm39)	missense	probably benign
R7556:Clcn3	UTSW	8	61,382,521 (GRCm39)	missense	probably damaging	0.99
R7557:Clcn3	UTSW	8	61,390,402 (GRCm39)	missense	probably damaging	0.99
R7685:Clcn3	UTSW	8	61,386,119 (GRCm39)	missense	possibly damaging	0.54
R7887:Clcn3	UTSW	8	61,394,433 (GRCm39)	missense	probably benign	0.16
R8219:Clcn3	UTSW	8	61,376,000 (GRCm39)	missense	probably damaging	0.98
R8478:Clcn3	UTSW	8	61,372,522 (GRCm39)	missense	probably benign
R8825:Clcn3	UTSW	8	61,382,522 (GRCm39)	missense	probably damaging	0.99
R9132:Clcn3	UTSW	8	61,382,136 (GRCm39)	missense	probably damaging	0.99
R9313:Clcn3	UTSW	8	61,390,503 (GRCm39)	missense	probably damaging	0.99
R9473:Clcn3	UTSW	8	61,407,651 (GRCm39)	missense	probably benign	0.01
R9475:Clcn3	UTSW	8	61,387,551 (GRCm39)	missense	probably damaging	0.96
R9598:Clcn3	UTSW	8	61,366,061 (GRCm39)	missense	unknown
R9697:Clcn3	UTSW	8	61,372,518 (GRCm39)	missense	probably damaging	1.00
R9718:Clcn3	UTSW	8	61,390,434 (GRCm39)	missense	possibly damaging	0.92

Predicted Primers

PCR Primer
(F):5'- GCATCTATACTACTCACCTACTGTGGGC -3'
(R):5'- GGTAAGTTCTCCATCCGTTCCTTATGTG -3'

Sequencing Primer
(F):5'- gtgagagagagagagagagagag -3'
(R):5'- ATCCGTTCCTTATGTGCCAGC -3'

Posted On

2013-05-23