Incidental Mutation 'R6750:Clcn3'
| ID |
530703 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Clcn3
|
| Ensembl Gene |
ENSMUSG00000004319 |
| Gene Name |
chloride channel, voltage-sensitive 3 |
| Synonyms |
Clc3 |
| MMRRC Submission |
044867-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly non essential
(E-score: 0.456)
|
| Stock # |
R6750 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
8 |
| Chromosomal Location |
61363423-61436334 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 61367809 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Proline
at position 780
(L780P)
|
| 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: L807P
PolyPhen 2
Score 0.931 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000004430
Gene: ENSMUSG00000004319
AA Change: L807P
| 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
|
| SMART Domains |
Protein: ENSMUSP00000058648
Gene: ENSMUSG00000004319
| 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 |
possibly damaging
Transcript: ENSMUST00000110302
AA Change: L780P
PolyPhen 2
Score 0.931 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000105931
Gene: ENSMUSG00000004319
AA Change: L780P
| 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: ENSMUST00000145741
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.5%
- 10x: 97.6%
- 20x: 92.7%
|
| Validation Efficiency |
100% (75/75) |
| 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: 73 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adal |
A |
T |
2: 120,973,130 (GRCm39) |
L62F |
probably damaging |
Het |
| Akap13 |
C |
T |
7: 75,389,206 (GRCm39) |
P2375S |
probably benign |
Het |
| Apob |
T |
A |
12: 8,047,853 (GRCm39) |
L931Q |
probably damaging |
Het |
| Arcn1 |
A |
G |
9: 44,661,691 (GRCm39) |
V391A |
possibly damaging |
Het |
| Ccdc162 |
A |
T |
10: 41,437,222 (GRCm39) |
I1729N |
possibly damaging |
Het |
| Cd24a |
T |
C |
10: 43,458,721 (GRCm39) |
L86P |
unknown |
Het |
| Cdcp3 |
T |
A |
7: 130,889,974 (GRCm39) |
|
probably benign |
Het |
| Churc1 |
C |
A |
12: 76,822,405 (GRCm39) |
H71Q |
probably damaging |
Het |
| Cldn17 |
C |
T |
16: 88,303,195 (GRCm39) |
G178E |
possibly damaging |
Het |
| Cmah |
A |
G |
13: 24,648,235 (GRCm39) |
Y345C |
probably damaging |
Het |
| Cntnap5b |
C |
T |
1: 100,202,224 (GRCm39) |
S357L |
probably damaging |
Het |
| Col6a6 |
A |
G |
9: 105,660,879 (GRCm39) |
I410T |
probably damaging |
Het |
| Crmp1 |
T |
C |
5: 37,422,666 (GRCm39) |
|
probably null |
Het |
| Csmd2 |
A |
C |
4: 128,091,018 (GRCm39) |
N186H |
possibly damaging |
Het |
| Cyp1a1 |
A |
T |
9: 57,607,539 (GRCm39) |
M56L |
probably benign |
Het |
| D2hgdh |
G |
C |
1: 93,754,129 (GRCm39) |
R56P |
probably benign |
Het |
| Dapk2 |
A |
G |
9: 66,128,034 (GRCm39) |
E104G |
probably damaging |
Het |
| Dld |
T |
C |
12: 31,382,213 (GRCm39) |
N498S |
probably benign |
Het |
| Dyrk4 |
G |
T |
6: 126,875,918 (GRCm39) |
Q106K |
probably benign |
Het |
| Eif2b4 |
T |
C |
5: 31,347,304 (GRCm39) |
I333V |
probably damaging |
Het |
| F5 |
A |
G |
1: 164,021,076 (GRCm39) |
T1184A |
possibly damaging |
Het |
| Fbxl6 |
C |
T |
15: 76,422,612 (GRCm39) |
G102D |
probably damaging |
Het |
| Foxa1 |
C |
T |
12: 57,589,396 (GRCm39) |
G275R |
probably benign |
Het |
| Fryl |
A |
G |
5: 73,179,575 (GRCm39) |
I2944T |
probably damaging |
Het |
| Gna15 |
T |
C |
10: 81,350,117 (GRCm39) |
D95G |
probably benign |
Het |
| Greb1 |
T |
A |
12: 16,738,584 (GRCm39) |
M1460L |
probably benign |
Het |
| Herc1 |
TCCC |
TCC |
9: 66,408,470 (GRCm39) |
|
probably null |
Het |
| Herc2 |
T |
C |
7: 55,747,195 (GRCm39) |
I444T |
probably damaging |
Het |
| Ifngr1 |
T |
A |
10: 19,485,099 (GRCm39) |
M366K |
probably benign |
Het |
| Krt27 |
C |
T |
11: 99,239,806 (GRCm39) |
E253K |
probably damaging |
Het |
| Mical2 |
C |
T |
7: 111,981,046 (GRCm39) |
T406I |
probably damaging |
Het |
| Mocs2 |
T |
G |
13: 114,962,784 (GRCm39) |
D156E |
probably damaging |
Het |
| Mprip |
A |
T |
11: 59,586,957 (GRCm39) |
K43N |
probably damaging |
Het |
| Myo5b |
A |
T |
18: 74,750,106 (GRCm39) |
T190S |
possibly damaging |
Het |
| Naa25 |
C |
T |
5: 121,546,372 (GRCm39) |
T86M |
probably damaging |
Het |
| Ncam1 |
T |
C |
9: 49,478,639 (GRCm39) |
D163G |
probably damaging |
Het |
| Nlrp4f |
A |
T |
13: 65,329,468 (GRCm39) |
Y908* |
probably null |
Het |
| Nlrp9b |
T |
A |
7: 19,757,159 (GRCm39) |
L132* |
probably null |
Het |
| Nrg1 |
A |
C |
8: 32,308,124 (GRCm39) |
S679A |
probably damaging |
Het |
| Or1j1 |
C |
A |
2: 36,702,954 (GRCm39) |
R50M |
possibly damaging |
Het |
| Or52p1 |
C |
T |
7: 104,267,320 (GRCm39) |
R145C |
probably damaging |
Het |
| Paqr9 |
A |
T |
9: 95,443,050 (GRCm39) |
T347S |
probably damaging |
Het |
| Pcdhb21 |
T |
C |
18: 37,647,501 (GRCm39) |
L210P |
probably damaging |
Het |
| Pdzd7 |
T |
G |
19: 45,016,187 (GRCm39) |
D978A |
probably benign |
Het |
| Phf8-ps |
A |
T |
17: 33,285,372 (GRCm39) |
S477T |
possibly damaging |
Het |
| Pkd1l1 |
A |
T |
11: 8,923,217 (GRCm39) |
S17T |
unknown |
Het |
| Plcz1 |
T |
C |
6: 139,974,164 (GRCm39) |
K93E |
possibly damaging |
Het |
| Pom121l2 |
G |
C |
13: 22,166,107 (GRCm39) |
R126P |
probably damaging |
Het |
| Prkg1 |
C |
T |
19: 31,741,961 (GRCm39) |
E88K |
probably benign |
Het |
| Psme4 |
A |
T |
11: 30,803,203 (GRCm39) |
D15V |
probably damaging |
Het |
| Ptprf |
A |
G |
4: 118,088,928 (GRCm39) |
V625A |
probably benign |
Het |
| Rab27a |
G |
A |
9: 72,992,290 (GRCm39) |
S106N |
probably damaging |
Het |
| Rasa4 |
A |
G |
5: 136,129,802 (GRCm39) |
T261A |
probably benign |
Het |
| Sardh |
T |
C |
2: 27,118,269 (GRCm39) |
D487G |
probably benign |
Het |
| Sec16a |
A |
G |
2: 26,330,030 (GRCm39) |
Y662H |
probably benign |
Het |
| Sema3d |
T |
A |
5: 12,635,067 (GRCm39) |
L711* |
probably null |
Het |
| Septin14 |
T |
A |
5: 129,773,181 (GRCm39) |
Y152F |
probably damaging |
Het |
| Smc5 |
A |
G |
19: 23,220,004 (GRCm39) |
L411P |
probably damaging |
Het |
| Spata31e5 |
C |
A |
1: 28,816,495 (GRCm39) |
E512D |
probably damaging |
Het |
| Spg7 |
T |
A |
8: 123,800,650 (GRCm39) |
V39E |
probably damaging |
Het |
| Tas2r117 |
A |
G |
6: 132,779,817 (GRCm39) |
|
probably benign |
Het |
| Tle1 |
A |
T |
4: 72,040,687 (GRCm39) |
I631N |
probably damaging |
Het |
| Tmed3 |
T |
A |
9: 89,581,843 (GRCm39) |
S207C |
probably damaging |
Het |
| Tmem59l |
G |
A |
8: 70,939,022 (GRCm39) |
P51S |
probably benign |
Het |
| Trpc3 |
A |
G |
3: 36,678,542 (GRCm39) |
Y848H |
probably damaging |
Het |
| Tsen2 |
T |
C |
6: 115,526,881 (GRCm39) |
F66S |
probably damaging |
Het |
| Ttll5 |
T |
A |
12: 86,003,384 (GRCm39) |
S216R |
probably damaging |
Het |
| Usp22 |
A |
T |
11: 61,048,042 (GRCm39) |
V426E |
probably damaging |
Het |
| Vmn2r76 |
T |
C |
7: 85,875,114 (GRCm39) |
N621S |
probably damaging |
Het |
| Wdr75 |
A |
G |
1: 45,856,539 (GRCm39) |
T521A |
probably damaging |
Het |
| Wrnip1 |
T |
A |
13: 32,986,739 (GRCm39) |
D173E |
probably damaging |
Het |
| Zfp317 |
G |
A |
9: 19,559,100 (GRCm39) |
G438D |
probably damaging |
Het |
| Zscan10 |
T |
A |
17: 23,826,164 (GRCm39) |
S109T |
possibly damaging |
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 |
|
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 |
|
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'- TCTGACGAGAGATGTTAGTTGC -3'
(R):5'- AGTTCATGAGGAGCATTCTTACG -3'
Sequencing Primer
(F):5'- ACGAGAGATGTTAGTTGCTGCTTAC -3'
(R):5'- CATGAGGAGCATTCTTACGGTTTATG -3'
|
| Posted On |
2018-08-01 |
Incidental Mutation