Mutagenetix > Incidental Mutation

Incidental Mutation 'R7757:Clcn7'

597644

Institutional Source

Beutler Lab

Gene Symbol

Clcn7

Ensembl Gene

ENSMUSG00000036636

Gene Name

chloride channel, voltage-sensitive 7

Synonyms

ClC-7

MMRRC Submission

045813-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7757 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

25352365-25381078 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 25375796 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 545 (Y545H)

Ref Sequence

ENSEMBL: ENSMUSP00000035964 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000040729] [ENSMUST00000160961]

AlphaFold

O70496

Predicted Effect

probably damaging
Transcript: ENSMUST00000040729
AA Change: Y545H

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

SMART Domains

Protein: ENSMUSP00000035964
Gene: ENSMUSG00000036636
AA Change: Y545H

Domain	Start	End	E-Value	Type
low complexity region	60	74	N/A	INTRINSIC
Pfam:Voltage_CLC	183	594	1.5e-96	PFAM
CBS	632	687	8.38e-4	SMART
CBS	742	790	1.77e-11	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000160961
AA Change: Y525H

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

SMART Domains

Protein: ENSMUSP00000124194
Gene: ENSMUSG00000036636
AA Change: Y525H

Domain	Start	End	E-Value	Type
low complexity region	8	25	N/A	INTRINSIC
low complexity region	40	54	N/A	INTRINSIC
Pfam:Voltage_CLC	163	574	1.5e-93	PFAM
CBS	612	667	8.38e-4	SMART
CBS	722	770	1.77e-11	SMART

Predicted Effect

SMART Domains

Protein: ENSMUSP00000124527
Gene: ENSMUSG00000036636
AA Change: Y257H

Domain	Start	End	E-Value	Type
Pfam:Voltage_CLC	5	307	1.3e-48	PFAM

Meta Mutation Damage Score

0.9247

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.9%

Validation Efficiency

96% (70/73)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The product of this gene belongs to the CLC chloride channel family of proteins. Chloride channels play important roles in the plasma membrane and in intracellular organelles. This gene encodes chloride channel 7. Defects in this gene are the cause of osteopetrosis autosomal recessive type 4 (OPTB4), also called infantile malignant osteopetrosis type 2 as well as the cause of autosomal dominant osteopetrosis type 2 (OPTA2), also called autosomal dominant Albers-Schonberg disease or marble disease autosoml dominant. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit postnatal lethality, abnormal bone formation, including osteopetrosis, and retinal degeneration. Mice homozygous for a conditional allele exhibit lysosomal defects with neuronal degeneration and accumulationof giant lysosomes in renal tubule cells. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700049A03Rik	G	A	12: 71,236,187 (GRCm39)	M1179I	probably benign	Het
6430550D23Rik	T	C	2: 155,845,351 (GRCm39)	T18A	possibly damaging	Het
Acox2	T	C	14: 8,230,166 (GRCm38)	N659S	probably damaging	Het
Agk	T	C	6: 40,353,212 (GRCm39)	V192A	possibly damaging	Het
Ap3b1	T	A	13: 94,664,666 (GRCm39)		probably null	Het
Bche	T	A	3: 73,608,454 (GRCm39)	D324V	probably damaging	Het
Bsn	A	G	9: 107,991,939 (GRCm39)	I1271T	possibly damaging	Het
Capn12	T	C	7: 28,582,246 (GRCm39)	L120P	probably damaging	Het
Cep290	T	A	10: 100,399,296 (GRCm39)	S2273T	probably benign	Het
Ckap4	T	C	10: 84,364,331 (GRCm39)	E244G	probably damaging	Het
Cmya5	T	A	13: 93,234,780 (GRCm39)	T103S	possibly damaging	Het
Cplane1	A	T	15: 8,281,711 (GRCm39)	E2850V	unknown	Het
Cpne9	G	A	6: 113,261,406 (GRCm39)	V121M	possibly damaging	Het
Csmd2	T	A	4: 128,377,249 (GRCm39)	I2043N		Het
Disc1	A	G	8: 125,814,243 (GRCm39)	T36A	probably benign	Het
Disp2	T	C	2: 118,621,391 (GRCm39)	Y708H	probably damaging	Het
Dnah3	A	G	7: 119,670,793 (GRCm39)	V635A	probably benign	Het
Dnah3	A	T	7: 119,570,438 (GRCm39)		probably null	Het
Dync1li1	A	G	9: 114,538,345 (GRCm39)	H234R	possibly damaging	Het
Egfr	T	C	11: 16,839,966 (GRCm39)	V660A	possibly damaging	Het
Epb42	T	C	2: 120,858,200 (GRCm39)	R253G	possibly damaging	Het
Fat2	T	A	11: 55,202,247 (GRCm39)	T276S	probably benign	Het
Fcho2	A	G	13: 98,901,011 (GRCm39)		probably null	Het
Ginm1	A	T	10: 7,655,119 (GRCm39)	I41N	probably damaging	Het
Gm4744	A	G	6: 40,927,367 (GRCm39)		probably benign	Het
Gm49368	C	T	7: 127,711,398 (GRCm39)	R701C	probably damaging	Het
Gpr37	T	A	6: 25,688,207 (GRCm39)	I297F	probably benign	Het
Gprc5a	T	A	6: 135,056,342 (GRCm39)	I263N	possibly damaging	Het
Gys2	A	T	6: 142,400,177 (GRCm39)	S345T	probably benign	Het
Hk2	T	C	6: 82,719,896 (GRCm39)	M255V	possibly damaging	Het
Ibtk	A	C	9: 85,579,290 (GRCm39)	S1202A	possibly damaging	Het
Il23r	T	G	6: 67,400,965 (GRCm39)	D455A	probably benign	Het
Irs2	T	A	8: 11,056,522 (GRCm39)	K637*	probably null	Het
Jak2	T	C	19: 29,260,946 (GRCm39)	V314A	probably benign	Het
Mei1	C	T	15: 81,966,824 (GRCm39)		probably benign	Het
Mill1	T	C	7: 17,996,391 (GRCm39)	M69T	probably benign	Het
Mms22l	T	C	4: 24,598,884 (GRCm39)		probably null	Het
Mup8	C	A	4: 60,220,332 (GRCm39)	Q133H	probably benign	Het
Mup8	T	A	4: 60,220,333 (GRCm39)	Q133L	probably benign	Het
Mycbp2	A	T	14: 103,429,055 (GRCm39)	Y2374N	probably damaging	Het
Nbeal1	A	T	1: 60,296,609 (GRCm39)	K1166N	probably damaging	Het
Nlrc4	T	A	17: 74,755,191 (GRCm39)	R8S	probably benign	Het
Nrcam	C	T	12: 44,596,681 (GRCm39)	Q25*	probably null	Het
Nudt16	A	C	9: 105,008,760 (GRCm39)	M47R	probably damaging	Het
Nup62	T	C	7: 44,478,419 (GRCm39)	S145P	probably benign	Het
Or10d1	A	G	9: 39,483,761 (GRCm39)	W265R	probably benign	Het
Or4c117	T	C	2: 88,955,333 (GRCm39)	I247M	possibly damaging	Het
Osbpl1a	A	T	18: 13,066,657 (GRCm39)	V34D	probably benign	Het
Otogl	T	A	10: 107,712,782 (GRCm39)	N521Y	probably damaging	Het
Pcdhb14	T	A	18: 37,582,887 (GRCm39)	D664E	possibly damaging	Het
Pex5l	T	C	3: 33,136,300 (GRCm39)		probably benign	Het
Pkhd1	A	G	1: 20,632,639 (GRCm39)	L592P	probably damaging	Het
Plxdc2	A	G	2: 16,734,187 (GRCm39)	H480R	probably benign	Het
Rnf216	T	A	5: 143,065,991 (GRCm39)	K532N	probably damaging	Het
Schip1	C	A	3: 68,525,028 (GRCm39)	Q358K	probably damaging	Het
Sdc2	A	T	15: 33,028,233 (GRCm39)	E117V	possibly damaging	Het
Septin11	A	T	5: 93,319,323 (GRCm39)		probably null	Het
Shprh	A	T	10: 11,037,924 (GRCm39)	E420V	probably benign	Het
Ska1	T	A	18: 74,330,044 (GRCm39)	H232L	probably benign	Het
Slc36a4	A	G	9: 15,630,956 (GRCm39)	N25S	possibly damaging	Het
Slitrk3	G	A	3: 72,958,172 (GRCm39)	T200M	probably damaging	Het
Smad2	C	T	18: 76,421,084 (GRCm39)	H138Y	probably benign	Het
Snx21	T	C	2: 164,628,085 (GRCm39)	S34P	probably damaging	Het
Sos2	A	G	12: 69,695,359 (GRCm39)	V126A	probably damaging	Het
Srcap	C	T	7: 127,129,966 (GRCm39)	T596I	probably damaging	Het
Stk31	T	G	6: 49,383,877 (GRCm39)		probably null	Het
Stox1	T	C	10: 62,499,743 (GRCm39)	D939G	probably damaging	Het
Syne2	G	T	12: 76,108,553 (GRCm39)	C979F	possibly damaging	Het
Tanc2	C	A	11: 105,667,684 (GRCm39)	N88K	possibly damaging	Het
Tll2	A	T	19: 41,084,447 (GRCm39)	V677E	probably damaging	Het
Ttn	T	C	2: 76,748,834 (GRCm39)	T4072A	probably benign	Het
Unc13b	CAGAGC	CAGAGCGAGAGC	4: 43,177,341 (GRCm39)		probably benign	Het
Unc13b	CGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGC	CGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGC	4: 43,177,312 (GRCm39)		probably benign	Het
Unc13b	AGAGCC	AGAGCCCGAGCC	4: 43,177,330 (GRCm39)		probably benign	Het
Vmn2r43	A	T	7: 8,258,253 (GRCm39)	F320Y	possibly damaging	Het
Zscan4f	G	T	7: 11,135,205 (GRCm39)	G204*	probably null	Het

Other mutations in Clcn7

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00486:Clcn7	APN	17	25,370,097 (GRCm39)	missense	probably damaging	1.00
IGL01735:Clcn7	APN	17	25,370,090 (GRCm39)	missense	probably benign	0.13
IGL01912:Clcn7	APN	17	25,371,983 (GRCm39)	splice site	probably benign
IGL01936:Clcn7	APN	17	25,374,350 (GRCm39)	missense	probably benign	0.44
IGL02084:Clcn7	APN	17	25,376,899 (GRCm39)	missense	probably benign
IGL02121:Clcn7	APN	17	25,372,058 (GRCm39)	missense	possibly damaging	0.95
IGL02160:Clcn7	APN	17	25,368,004 (GRCm39)	unclassified	probably benign
IGL02335:Clcn7	APN	17	25,365,821 (GRCm39)	missense	probably benign	0.00
IGL02507:Clcn7	APN	17	25,363,443 (GRCm39)	missense	probably damaging	1.00
IGL02605:Clcn7	APN	17	25,365,792 (GRCm39)	missense	possibly damaging	0.60
IGL03160:Clcn7	APN	17	25,365,427 (GRCm39)	unclassified	probably benign
IGL03192:Clcn7	APN	17	25,352,575 (GRCm39)	missense	probably benign	0.00
IGL03194:Clcn7	APN	17	25,369,522 (GRCm39)	missense	probably damaging	0.98
IGL03409:Clcn7	APN	17	25,374,359 (GRCm39)	missense	probably damaging	1.00
R0140:Clcn7	UTSW	17	25,372,728 (GRCm39)	missense	probably damaging	1.00
R0153:Clcn7	UTSW	17	25,368,176 (GRCm39)	unclassified	probably benign
R0970:Clcn7	UTSW	17	25,370,208 (GRCm39)	critical splice donor site	probably null
R1644:Clcn7	UTSW	17	25,378,672 (GRCm39)	missense	probably damaging	1.00
R1856:Clcn7	UTSW	17	25,379,445 (GRCm39)	missense	probably damaging	1.00
R2145:Clcn7	UTSW	17	25,363,425 (GRCm39)	missense	probably benign
R2173:Clcn7	UTSW	17	25,364,583 (GRCm39)	missense	probably benign
R2401:Clcn7	UTSW	17	25,372,114 (GRCm39)	missense	probably benign	0.02
R2511:Clcn7	UTSW	17	25,374,420 (GRCm39)	missense	probably damaging	1.00
R3683:Clcn7	UTSW	17	25,369,567 (GRCm39)	missense	possibly damaging	0.84
R3684:Clcn7	UTSW	17	25,369,567 (GRCm39)	missense	possibly damaging	0.84
R3694:Clcn7	UTSW	17	25,378,681 (GRCm39)	missense	probably damaging	0.99
R4424:Clcn7	UTSW	17	25,379,150 (GRCm39)	missense	probably damaging	1.00
R4681:Clcn7	UTSW	17	25,376,935 (GRCm39)	missense	probably damaging	1.00
R4870:Clcn7	UTSW	17	25,372,539 (GRCm39)	intron	probably benign
R5372:Clcn7	UTSW	17	25,376,153 (GRCm39)	missense	possibly damaging	0.82
R5820:Clcn7	UTSW	17	25,368,026 (GRCm39)	missense	probably damaging	1.00
R6154:Clcn7	UTSW	17	25,376,928 (GRCm39)	missense	probably damaging	0.98
R6181:Clcn7	UTSW	17	25,370,702 (GRCm39)	missense	possibly damaging	0.79
R6306:Clcn7	UTSW	17	25,376,502 (GRCm39)	missense	probably benign	0.01
R6798:Clcn7	UTSW	17	25,378,734 (GRCm39)	missense	probably damaging	1.00
R6961:Clcn7	UTSW	17	25,376,188 (GRCm39)	missense	probably damaging	1.00
R7020:Clcn7	UTSW	17	25,365,325 (GRCm39)	missense	possibly damaging	0.76
R7089:Clcn7	UTSW	17	25,372,667 (GRCm39)	missense
R8057:Clcn7	UTSW	17	25,368,233 (GRCm39)	nonsense	probably null
R8670:Clcn7	UTSW	17	25,378,588 (GRCm39)	missense	probably damaging	0.99
R9031:Clcn7	UTSW	17	25,376,497 (GRCm39)	missense	probably damaging	0.96
R9720:Clcn7	UTSW	17	25,374,471 (GRCm39)	missense	probably damaging	1.00
X0020:Clcn7	UTSW	17	25,369,200 (GRCm39)	missense	probably damaging	1.00
Z1177:Clcn7	UTSW	17	25,371,989 (GRCm39)	critical splice acceptor site	probably null

Predicted Primers

PCR Primer
(F):5'- GCAAGTGGCATAGTCTGTACC -3'
(R):5'- CGTGCTATGGACCTGATGAC -3'

Sequencing Primer
(F):5'- TGGCACACCTAGCTAGAGTGTTC -3'
(R):5'- GATGACCTCATCTGCCTCAC -3'

Posted On

2019-11-26