Mutagenetix > Incidental Mutation

Incidental Mutation 'R5112:Clcn3'

393936

Institutional Source

Beutler Lab

Gene Symbol

Clcn3

Ensembl Gene

ENSMUSG00000004319

Gene Name

chloride channel, voltage-sensitive 3

Synonyms

Clc3

MMRRC Submission

042700-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.447) question?

Stock #

R5112 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

61363423-61436334 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 61407586 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Tyrosine at position 24 (H24Y)

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

probably benign
Transcript: ENSMUST00000004430

SMART Domains

Protein: ENSMUSP00000004430
Gene: ENSMUSG00000004319

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: H24Y

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000058648
Gene: ENSMUSG00000004319
AA Change: H24Y

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

SMART Domains

Protein: ENSMUSP00000091202
Gene: ENSMUSG00000004319

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

SMART Domains

Protein: ENSMUSP00000105930
Gene: ENSMUSG00000004319

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

probably benign
Transcript: ENSMUST00000110302
AA Change: H24Y

PolyPhen 2 Score 0.071 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000105931
Gene: ENSMUSG00000004319
AA Change: H24Y

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

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.4%
20x: 92.6%

Validation Efficiency

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: 103 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca2	A	G	2: 25,328,383 (GRCm39)	K846R	probably damaging	Het
Acsbg3	T	A	17: 57,184,465 (GRCm39)	M80K	probably benign	Het
Acsm5	A	G	7: 119,136,502 (GRCm39)	K358E	possibly damaging	Het
Adam26a	A	T	8: 44,021,893 (GRCm39)	D532E	probably benign	Het
Adamts19	C	T	18: 59,164,876 (GRCm39)	R993*	probably null	Het
Akr1c13	A	G	13: 4,244,151 (GRCm39)	K68R	possibly damaging	Het
Amer3	T	A	1: 34,626,157 (GRCm39)	M132K	possibly damaging	Het
Ankrd2	A	G	19: 42,028,326 (GRCm39)	D38G	possibly damaging	Het
Ano7	G	A	1: 93,325,085 (GRCm39)	V546M	possibly damaging	Het
Aox1	G	A	1: 58,349,254 (GRCm39)		probably null	Het
Apc	T	A	18: 34,449,162 (GRCm39)	C1985*	probably null	Het
Astn1	C	T	1: 158,484,763 (GRCm39)	S15F	possibly damaging	Het
Atp13a4	A	T	16: 29,228,686 (GRCm39)	N950K	possibly damaging	Het
Bcl6	A	G	16: 23,791,496 (GRCm39)	V286A	probably benign	Het
Brox	T	A	1: 183,073,541 (GRCm39)	T79S	probably benign	Het
C2cd3	A	T	7: 100,092,692 (GRCm39)	I512F	possibly damaging	Het
Camta1	A	G	4: 151,158,511 (GRCm39)	L542S	probably damaging	Het
Capn13	GCA	G	17: 73,658,501 (GRCm39)		probably null	Het
Card10	C	T	15: 78,686,580 (GRCm39)		probably null	Het
Cd96	A	G	16: 45,919,301 (GRCm39)	M240T	probably benign	Het
Cdc123	A	G	2: 5,809,748 (GRCm39)	L221P	possibly damaging	Het
Cdh19	A	G	1: 110,882,354 (GRCm39)	V46A	possibly damaging	Het
Col11a2	T	C	17: 34,283,062 (GRCm39)		probably benign	Het
Cpsf3	A	T	12: 21,341,785 (GRCm39)	M50L	probably benign	Het
Csf3	T	A	11: 98,593,749 (GRCm39)	L197Q	probably damaging	Het
Ctsw	T	A	19: 5,516,285 (GRCm39)	D196V	probably damaging	Het
Dcun1d3	A	T	7: 119,457,250 (GRCm39)	I154K	probably damaging	Het
Ddr1	T	C	17: 35,993,377 (GRCm39)	T877A	probably benign	Het
Dnah8	T	A	17: 30,950,012 (GRCm39)	L1944I	probably benign	Het
Dpf3	G	T	12: 83,417,385 (GRCm39)	S29*	probably null	Het
Ephb1	A	G	9: 101,848,378 (GRCm39)	I640T	probably damaging	Het
Fat1	G	A	8: 45,477,319 (GRCm39)	G2099S	probably damaging	Het
Fbxo41	G	T	6: 85,454,906 (GRCm39)	N667K	probably damaging	Het
Flacc1	T	C	1: 58,698,441 (GRCm39)	T326A	probably benign	Het
Gart	A	T	16: 91,430,933 (GRCm39)	D376E	probably benign	Het
Glyr1	G	A	16: 4,836,740 (GRCm39)	Q475*	probably null	Het
Gm28051	G	A	12: 102,686,430 (GRCm39)	Q77*	probably null	Het
Gnmt	C	A	17: 47,037,256 (GRCm39)	R176L	probably damaging	Het
Gpr176	A	T	2: 118,110,629 (GRCm39)	V210D	possibly damaging	Het
Gtf2ird1	A	T	5: 134,431,038 (GRCm39)	D339E	probably damaging	Het
Hmbox1	A	G	14: 65,063,061 (GRCm39)	Y372H	probably damaging	Het
Ier2	G	T	8: 85,389,361 (GRCm39)	A7E	probably damaging	Het
Il20ra	A	G	10: 19,634,691 (GRCm39)	T311A	possibly damaging	Het
Il24	T	C	1: 130,811,179 (GRCm39)		probably null	Het
Insl6	G	A	19: 29,298,996 (GRCm39)	Q139*	probably null	Het
Itga2b	A	T	11: 102,349,017 (GRCm39)	I729K	probably damaging	Het
Itpr2	A	T	6: 146,135,489 (GRCm39)	M1814K	possibly damaging	Het
Klhl3	G	A	13: 58,166,703 (GRCm39)	S429F	probably damaging	Het
Lipo2	T	C	19: 33,725,865 (GRCm39)	N129S	probably benign	Het
Lrba	C	T	3: 86,132,678 (GRCm39)	T28M	probably benign	Het
Ly86	G	T	13: 37,559,013 (GRCm39)	G71C	probably damaging	Het
Maob	T	C	X: 16,582,662 (GRCm39)	T400A	probably benign	Het
Mical2	A	G	7: 111,919,818 (GRCm39)	S443G	probably damaging	Het
Mmp17	A	G	5: 129,679,229 (GRCm39)	H376R	possibly damaging	Het
Mplkipl1	C	T	19: 61,164,364 (GRCm39)	G24R	unknown	Het
Myo7b	T	C	18: 32,116,640 (GRCm39)	H989R	probably damaging	Het
Neil2	A	G	14: 63,425,909 (GRCm39)	W154R	probably damaging	Het
Nlrp12	G	A	7: 3,289,613 (GRCm39)	H300Y	possibly damaging	Het
Nlrp3	A	T	11: 59,439,554 (GRCm39)	Y377F	probably damaging	Het
Notch2	T	C	3: 98,008,952 (GRCm39)		probably null	Het
Nudcd1	A	T	15: 44,240,039 (GRCm39)	C500*	probably null	Het
Or5b24	T	C	19: 12,912,180 (GRCm39)	V26A	probably benign	Het
Or5d37	A	G	2: 87,923,353 (GRCm39)	V309A	probably damaging	Het
Or8g18	A	G	9: 39,149,717 (GRCm39)	M1T	probably null	Het
Or8h9	A	T	2: 86,789,698 (GRCm39)	Y35N	probably damaging	Het
Pabpc6	T	A	17: 9,888,540 (GRCm39)	S4C	probably damaging	Het
Pan2	C	T	10: 128,151,464 (GRCm39)	R835*	probably null	Het
Parp9	G	A	16: 35,784,683 (GRCm39)	V346I	probably damaging	Het
Pcbp4	C	T	9: 106,337,917 (GRCm39)	T69M	probably damaging	Het
Pclo	T	A	5: 14,727,896 (GRCm39)		probably benign	Het
Phldb3	A	T	7: 24,324,110 (GRCm39)	I495F	possibly damaging	Het
Plce1	G	T	19: 38,640,277 (GRCm39)	V508F	probably benign	Het
Pmpca	A	T	2: 26,285,178 (GRCm39)	I468F	probably damaging	Het
Pmpcb	G	A	5: 21,961,441 (GRCm39)	R399H	probably damaging	Het
Ptprc	A	G	1: 138,022,037 (GRCm39)	S544P	probably damaging	Het
Rev3l	T	A	10: 39,699,326 (GRCm39)	D1274E	probably benign	Het
Ryr3	A	T	2: 112,733,010 (GRCm39)	V612E	probably damaging	Het
Scfd2	G	T	5: 74,366,982 (GRCm39)	H639Q	probably benign	Het
Sell	T	A	1: 163,892,887 (GRCm39)	H34Q	possibly damaging	Het
Setd2	A	G	9: 110,377,226 (GRCm39)	D347G	probably benign	Het
Sgip1	G	A	4: 102,726,966 (GRCm39)	D81N	probably damaging	Het
Slc12a1	A	T	2: 125,060,144 (GRCm39)	I940F	possibly damaging	Het
Slc25a34	T	A	4: 141,348,769 (GRCm39)	I232L	probably benign	Het
Slc36a3	T	A	11: 55,039,399 (GRCm39)	K76N	probably damaging	Het
Slc6a15	T	A	10: 103,225,087 (GRCm39)	D58E	probably benign	Het
Slc6a7	T	C	18: 61,140,448 (GRCm39)	S195G	probably null	Het
Svep1	G	A	4: 58,068,610 (GRCm39)	Q3059*	probably null	Het
Syce1l	A	C	8: 114,378,274 (GRCm39)	H56P	probably damaging	Het
Tbc1d2	A	G	4: 46,606,503 (GRCm39)	V814A	probably damaging	Het
Tbx18	T	A	9: 87,597,740 (GRCm39)	I265F	probably damaging	Het
Thbs2	T	C	17: 14,890,852 (GRCm39)		probably null	Het
Ttll1	T	C	15: 83,380,597 (GRCm39)	H256R	probably damaging	Het
Ttn	A	T	2: 76,641,587 (GRCm39)	L5176Q	possibly damaging	Het
Ttyh2	A	T	11: 114,587,583 (GRCm39)	T195S	probably benign	Het
Unc119b	A	G	5: 115,263,553 (GRCm39)	L217P	probably damaging	Het
Unc5a	T	C	13: 55,151,231 (GRCm39)		probably null	Het
Usp6nl	A	G	2: 6,425,714 (GRCm39)	K152E	probably benign	Het
Vcam1	T	C	3: 115,910,941 (GRCm39)	R486G	probably benign	Het
Vmn2r1	A	C	3: 63,997,544 (GRCm39)	Q400P	possibly damaging	Het
Vmn2r80	T	A	10: 79,030,292 (GRCm39)	V706D	possibly damaging	Het
Vmn2r87	A	T	10: 130,314,422 (GRCm39)	L388Q	probably damaging	Het
Vwa3a	A	T	7: 120,383,208 (GRCm39)	Y603F	probably damaging	Het
Zfp850	A	T	7: 27,689,658 (GRCm39)	C183*	probably null	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
R0437:Clcn3	UTSW	8	61,387,571 (GRCm39)	missense	possibly damaging	0.69
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
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'- CACTGCTAATCGCCACAGAG -3'
(R):5'- TCAGCCAGTCGAACTATGCAG -3'

Sequencing Primer
(F):5'- TGCTAATCGCCACAGAGCAAAC -3'
(R):5'- GCAGTTCTAACCTCATCAAATATGGC -3'

Posted On

2016-06-15