Mutagenetix > Incidental Mutation

Incidental Mutation 'R5011:Clcn2'

390543

Institutional Source

Beutler Lab

Gene Symbol

Clcn2

Ensembl Gene

ENSMUSG00000022843

Gene Name

chloride channel, voltage-sensitive 2

Synonyms

ClC-2, nmf240, Clc2

MMRRC Submission

042602-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.483) question?

Stock #

R5011 (G1)

Quality Score

214

Status

Validated

Chromosome

Chromosomal Location

20702964-20717746 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 20707215 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Proline to Serine at position 785 (P785S)

Ref Sequence

ENSEMBL: ENSMUSP00000112759 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000007207] [ENSMUST00000056518] [ENSMUST00000118919] [ENSMUST00000120099] [ENSMUST00000131522] [ENSMUST00000232309]

AlphaFold

Q9R0A1

Predicted Effect

probably damaging
Transcript: ENSMUST00000007207
AA Change: P802S

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000007207
Gene: ENSMUSG00000022843
AA Change: P802S

Domain	Start	End	E-Value	Type
low complexity region	2	14	N/A	INTRINSIC
low complexity region	102	111	N/A	INTRINSIC
Pfam:Voltage_CLC	151	555	1.2e-94	PFAM
Blast:CBS	595	644	3e-12	BLAST
low complexity region	666	680	N/A	INTRINSIC
CBS	803	850	3.69e0	SMART
low complexity region	869	881	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000056518

SMART Domains

Protein: ENSMUSP00000060194
Gene: ENSMUSG00000050821

Domain	Start	End	E-Value	Type
low complexity region	45	60	N/A	INTRINSIC
Pfam:FAM131	80	356	6.4e-144	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000118919

SMART Domains

Protein: ENSMUSP00000113719
Gene: ENSMUSG00000050821

Domain	Start	End	E-Value	Type
Pfam:FAM131	1	271	4e-119	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000120099
AA Change: P785S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000112759
Gene: ENSMUSG00000022843
AA Change: P785S

Domain	Start	End	E-Value	Type
low complexity region	2	14	N/A	INTRINSIC
low complexity region	102	111	N/A	INTRINSIC
Pfam:Voltage_CLC	151	538	5.6e-77	PFAM
Blast:CBS	578	627	4e-12	BLAST
low complexity region	649	663	N/A	INTRINSIC
CBS	786	833	3.69e0	SMART
low complexity region	852	864	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123417

Predicted Effect

probably benign
Transcript: ENSMUST00000131522

SMART Domains

Protein: ENSMUSP00000122921
Gene: ENSMUSG00000022843

Domain	Start	End	E-Value	Type
low complexity region	2	14	N/A	INTRINSIC
low complexity region	102	111	N/A	INTRINSIC
Pfam:Voltage_CLC	151	473	4.2e-63	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000131833

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144400

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000148131

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153075

Predicted Effect

probably benign
Transcript: ENSMUST00000231381

Predicted Effect

probably damaging
Transcript: ENSMUST00000232309
AA Change: P758S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

Meta Mutation Damage Score

0.3258

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.5%

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 voltage-gated chloride channel. The encoded protein is a transmembrane protein that maintains chloride ion homeostasis in various cells. Defects in this gene may be a cause of certain epilepsies. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]
PHENOTYPE: Mice homozygous for a null allele exhibit abnormal brain morphology, male infertility, and abnormal eye morphology. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1810010H24Rik	T	C	11: 107,028,498	V223A	probably damaging	Het
2700049A03Rik	A	T	12: 71,164,547	E685V	possibly damaging	Het
2700049A03Rik	G	T	12: 71,164,546	E685*	probably null	Het
A630095E13Rik	T	C	9: 36,637,824	N47D	probably benign	Het
Ahctf1	A	T	1: 179,784,110	I565N	possibly damaging	Het
Ank1	C	T	8: 23,082,284	T70I	probably damaging	Het
Atg16l1	C	A	1: 87,774,180	S248*	probably null	Het
Atp13a5	A	T	16: 29,350,748	L42Q	probably damaging	Het
Atxn1	T	C	13: 45,557,069	N796D	probably damaging	Het
C3	T	A	17: 57,223,236	Y455F	probably benign	Het
Card11	A	T	5: 140,876,520	D1007E	possibly damaging	Het
Cbr2	T	C	11: 120,730,871	D60G	possibly damaging	Het
Cgn	T	A	3: 94,776,145	E400V	probably null	Het
Chil3	T	A	3: 106,150,161	Y229F	possibly damaging	Het
Clk1	T	C	1: 58,414,483	I315V	probably benign	Het
Cops6	A	G	5: 138,162,197	D102G	probably benign	Het
Dennd5a	A	G	7: 109,914,776	I743T	possibly damaging	Het
Dnaaf5	T	A	5: 139,163,257	L437Q	probably damaging	Het
Dnah12	T	A	14: 26,710,171	D381E	probably benign	Het
Dnah8	G	A	17: 30,748,568	D2585N	probably benign	Het
Draxin	C	A	4: 148,107,979	R292L	probably damaging	Het
Dst	T	C	1: 34,250,647	V5776A	probably damaging	Het
Epp13	G	A	7: 6,266,333		probably benign	Het
Ercc4	G	A	16: 13,123,581		probably benign	Het
Eya1	T	A	1: 14,184,358	N417Y	probably damaging	Het
Fam149b	T	A	14: 20,363,371	H219Q	possibly damaging	Het
Fam227b	G	A	2: 126,116,123	P241S	probably damaging	Het
Fat1	A	T	8: 45,031,263		probably null	Het
Fbxl18	A	G	5: 142,886,680	S267P	probably damaging	Het
Fer1l4	T	C	2: 156,031,215	Y1315C	probably damaging	Het
Fgd2	T	C	17: 29,374,980		probably null	Het
Gm7251	T	A	13: 49,805,180		noncoding transcript	Het
Golt1a	T	C	1: 133,320,268	V78A	probably damaging	Het
Gsn	T	A	2: 35,298,921	Y440N	probably damaging	Het
Gtf2ird2	G	T	5: 134,216,982	S694I	possibly damaging	Het
H2-Ob	T	A	17: 34,241,279		probably null	Het
Hsp90b1	T	C	10: 86,696,753	D353G	probably benign	Het
Ilk	A	G	7: 105,742,249	D374G	probably damaging	Het
Invs	G	A	4: 48,421,807	R813Q	probably damaging	Het
Itga7	G	A	10: 128,949,447	V836M	possibly damaging	Het
Itln1	T	A	1: 171,533,390	K45*	probably null	Het
Ivd	A	G	2: 118,880,465	Y385C	probably damaging	Het
Ivns1abp	T	A	1: 151,363,202	M589K	possibly damaging	Het
Jakmip3	C	T	7: 139,020,222	R284W	probably damaging	Het
Kank3	T	C	17: 33,822,070	L512P	probably damaging	Het
Kcnn2	T	A	18: 45,685,285	I483N	possibly damaging	Het
Klk1b4	A	G	7: 44,211,068	N170S	probably benign	Het
Klk9	A	C	7: 43,795,995	D203A	probably damaging	Het
Lbr	A	T	1: 181,819,888	Y199*	probably null	Het
Lcn6	T	A	2: 25,677,070		probably null	Het
Lrriq1	T	C	10: 103,189,923	D946G	probably damaging	Het
Ltbp1	T	A	17: 75,066,157	L265H	probably damaging	Het
Maml3	A	T	3: 51,690,775	N183K	possibly damaging	Het
Mprip	T	C	11: 59,759,895	V1475A	possibly damaging	Het
Myh4	C	A	11: 67,256,363	S1611R	probably benign	Het
Nagpa	A	T	16: 5,195,879	M365K	probably benign	Het
Nckap5l	G	T	15: 99,426,576	P682Q	probably benign	Het
Nudt12	T	C	17: 58,996,504		probably benign	Het
Nup153	T	C	13: 46,687,403	T910A	possibly damaging	Het
Olfr1055	A	T	2: 86,347,303	F154L	probably benign	Het
Olfr291	T	C	7: 84,856,438	V23A	probably damaging	Het
Olfr367-ps	A	G	2: 37,270,925		noncoding transcript	Het
Olfr391-ps	T	A	11: 73,799,647	T37S	possibly damaging	Het
Pbx2	T	A	17: 34,594,699	C224*	probably null	Het
Pcdha6	A	G	18: 36,967,907	D51G	probably damaging	Het
Pnpla1	C	T	17: 28,885,584	T538I	possibly damaging	Het
Pnpla2	T	C	7: 141,459,291		probably null	Het
Psme2b	C	T	11: 48,945,827	E98K	probably benign	Het
Ranbp2	T	A	10: 58,461,895	S375T	probably benign	Het
Rimbp2	T	C	5: 128,803,921	Y134C	probably damaging	Het
Ryr1	G	A	7: 29,102,809		probably null	Het
Sh3tc1	G	T	5: 35,700,289	A1185D	probably damaging	Het
Sin3b	G	A	8: 72,744,556	S377N	probably benign	Het
Slc28a2	T	C	2: 122,457,890	M554T	possibly damaging	Het
Snhg11	T	C	2: 158,376,952		probably benign	Het
Spink5	A	T	18: 44,006,412	N614I	probably damaging	Het
Tert	T	C	13: 73,646,309		probably null	Het
Thap4	T	C	1: 93,749,876	Y396C	probably damaging	Het
Tle2	T	C	10: 81,584,697	L348P	probably damaging	Het
Tmem104	T	C	11: 115,243,486	S283P	probably damaging	Het
Tnn	T	C	1: 160,126,379	E602G	possibly damaging	Het
Tpm4	A	G	8: 72,147,094	K190R	probably benign	Het
Ttf2	T	C	3: 100,963,169	E196G	probably benign	Het
Ugt3a2	T	C	15: 9,365,287	W329R	probably damaging	Het
Unc13a	G	A	8: 71,641,477	Q1327*	probably null	Het
Vmn1r194	C	T	13: 22,244,888	T225I	probably benign	Het
Vmn1r215	T	C	13: 23,076,551	S254P	probably damaging	Het
Vmn2r109	T	C	17: 20,555,189	E92G	probably damaging	Het
Ythdc2	A	G	18: 44,854,742	M625V	probably benign	Het
Zfp106	A	G	2: 120,510,534	W1832R	probably damaging	Het
Zfp189	G	A	4: 49,530,438	G514S	probably damaging	Het
Zfp768	T	C	7: 127,343,703	R418G	probably damaging	Het
Zmynd11	C	T	13: 9,689,443		probably benign	Het

Other mutations in Clcn2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00843:Clcn2	APN	16	20,703,641 (GRCm38)	missense	probably benign	0.08
IGL01657:Clcn2	APN	16	20,713,619 (GRCm38)	missense	probably damaging	1.00
IGL01797:Clcn2	APN	16	20,712,761 (GRCm38)	missense	probably damaging	1.00
IGL02557:Clcn2	APN	16	20,708,464 (GRCm38)	missense	probably damaging	1.00
IGL02624:Clcn2	APN	16	20,703,348 (GRCm38)	missense	probably damaging	0.98
IGL02819:Clcn2	APN	16	20,709,256 (GRCm38)	nonsense	probably null
IGL03329:Clcn2	APN	16	20,712,152 (GRCm38)	missense	probably damaging	1.00
Bemr14	UTSW	16	0 ()	unclassified
R0008:Clcn2	UTSW	16	20,710,390 (GRCm38)	missense	probably null	1.00
R0454:Clcn2	UTSW	16	20,710,428 (GRCm38)	critical splice acceptor site	probably null
R1101:Clcn2	UTSW	16	20,703,595 (GRCm38)	missense	probably damaging	1.00
R1466:Clcn2	UTSW	16	20,712,552 (GRCm38)	splice site	probably benign
R1824:Clcn2	UTSW	16	20,715,962 (GRCm38)	missense	probably benign	0.04
R4592:Clcn2	UTSW	16	20,709,142 (GRCm38)	missense	probably damaging	0.99
R5013:Clcn2	UTSW	16	20,707,215 (GRCm38)	missense	probably damaging	1.00
R5154:Clcn2	UTSW	16	20,703,303 (GRCm38)	missense	probably benign	0.01
R5374:Clcn2	UTSW	16	20,709,669 (GRCm38)	missense	possibly damaging	0.78
R5726:Clcn2	UTSW	16	20,710,535 (GRCm38)	intron	probably benign
R5787:Clcn2	UTSW	16	20,703,433 (GRCm38)	missense	probably damaging	1.00
R5992:Clcn2	UTSW	16	20,713,654 (GRCm38)	missense	possibly damaging	0.68
R6045:Clcn2	UTSW	16	20,711,688 (GRCm38)	critical splice donor site	probably null
R6663:Clcn2	UTSW	16	20,703,245 (GRCm38)	makesense	probably null
R6765:Clcn2	UTSW	16	20,707,668 (GRCm38)	splice site	probably null
R6825:Clcn2	UTSW	16	20,709,658 (GRCm38)	utr 3 prime	probably benign
R7872:Clcn2	UTSW	16	20,708,460 (GRCm38)	missense	probably damaging	0.99
R8028:Clcn2	UTSW	16	20,708,762 (GRCm38)	missense	possibly damaging	0.66
R8198:Clcn2	UTSW	16	20,707,196 (GRCm38)	missense	probably damaging	0.99
R8805:Clcn2	UTSW	16	20,713,418 (GRCm38)	missense	probably damaging	1.00
R8924:Clcn2	UTSW	16	20,712,180 (GRCm38)	missense	probably damaging	1.00
R8992:Clcn2	UTSW	16	20,712,330 (GRCm38)	missense	probably damaging	1.00
R9074:Clcn2	UTSW	16	20,712,664 (GRCm38)	missense	possibly damaging	0.78
R9101:Clcn2	UTSW	16	20,707,229 (GRCm38)	missense	probably benign	0.00
R9456:Clcn2	UTSW	16	20,715,952 (GRCm38)	small deletion	probably benign

Predicted Primers

PCR Primer
(F):5'- GGCTTACAGACTTACATGGCTG -3'
(R):5'- TAGAGTGACTCAGACCCGGAAG -3'

Sequencing Primer
(F):5'- GCTTACAGACTTACATGGCTGAAAGC -3'
(R):5'- ATGCCATTAGACTCTAGAGGGTTTC -3'

Posted On

2016-06-06