Incidental Mutation 'IGL02041:Clcn3'
ID184745
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Clcn3
Ensembl Gene ENSMUSG00000004319
Gene Namechloride channel, voltage-sensitive 3
SynonymsClc3
Accession Numbers
Is this an essential gene? Possibly non essential (E-score: 0.491) question?
Stock #IGL02041
Quality Score
Status
Chromosome8
Chromosomal Location60910389-60983300 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to C at 60923153 bp
ZygosityHeterozygous
Amino Acid Change Isoleucine to Valine at position 596 (I596V)
Ref Sequence ENSEMBL: ENSMUSP00000105930 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000004430] [ENSMUST00000056508] [ENSMUST00000093490] [ENSMUST00000110301] [ENSMUST00000110302]
Predicted Effect possibly damaging
Transcript: ENSMUST00000004430
AA Change: I596V

PolyPhen 2 Score 0.888 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000004430
Gene: ENSMUSG00000004319
AA Change: I596V

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000056508
AA Change: I569V

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000058648
Gene: ENSMUSG00000004319
AA Change: I569V

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000093490
AA Change: I538V

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000091202
Gene: ENSMUSG00000004319
AA Change: I538V

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000110301
AA Change: I596V

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000105930
Gene: ENSMUSG00000004319
AA Change: I596V

DomainStartEndE-ValueType
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: I569V

PolyPhen 2 Score 0.888 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000105931
Gene: ENSMUSG00000004319
AA Change: I569V

DomainStartEndE-ValueType
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
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: 46 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc2 A T 19: 43,784,235 Q28L probably damaging Het
Afg1l A G 10: 42,454,380 V97A probably damaging Het
Akap6 A C 12: 53,140,653 S1617R probably damaging Het
Aldh1a3 T C 7: 66,407,831 N285D probably damaging Het
Arhgap20 A T 9: 51,846,190 N494I possibly damaging Het
Atg9a G T 1: 75,183,104 Q712K possibly damaging Het
Btbd11 G A 10: 85,387,554 D76N unknown Het
Cdcp2 G A 4: 107,107,189 probably benign Het
Cds2 T A 2: 132,294,443 I84N possibly damaging Het
Ctxn1 A G 8: 4,258,514 L39P probably damaging Het
Efhb A T 17: 53,426,259 V528D probably damaging Het
Fmod T G 1: 134,040,263 S14A probably benign Het
Foxh1 A G 15: 76,668,920 F198S probably damaging Het
Gcc2 A G 10: 58,269,281 E77G probably damaging Het
Gm5420 G T 10: 21,691,034 noncoding transcript Het
Gm6434 T G 7: 25,882,230 noncoding transcript Het
Il1b A T 2: 129,369,742 N19K possibly damaging Het
Lama2 T A 10: 26,984,326 D3055V probably damaging Het
Lcn3 G A 2: 25,765,624 V18I probably benign Het
Lpcat2 A G 8: 92,918,181 S533G probably benign Het
Map4k2 G A 19: 6,351,318 R606Q probably benign Het
Mtnr1b T C 9: 15,863,293 T157A probably benign Het
Myo15 G A 11: 60,506,863 E2705K probably damaging Het
Ncf2 A G 1: 152,836,120 probably benign Het
Nfkbil1 G A 17: 35,220,958 T193M probably benign Het
Nmi T G 2: 51,960,629 K9T possibly damaging Het
Olfr494 T C 7: 108,367,535 F15S probably damaging Het
Olfr710 T C 7: 106,944,113 D296G possibly damaging Het
Olfr804 A G 10: 129,705,235 D119G probably damaging Het
Osbpl7 T A 11: 97,060,508 C502S probably benign Het
Pex5 A T 6: 124,405,281 probably benign Het
Pkhd1l1 T A 15: 44,493,056 probably null Het
Prmt3 C T 7: 49,828,963 T424M possibly damaging Het
Rapgef4 G A 2: 72,198,796 G404D probably damaging Het
Rbm5 C T 9: 107,755,846 probably benign Het
Rfc2 T A 5: 134,594,244 F238L probably benign Het
Rsl1 A G 13: 67,176,548 E46G probably damaging Het
Sall1 A G 8: 89,031,469 F669S probably damaging Het
Sipa1l2 A G 8: 125,491,819 S260P probably benign Het
Slc26a8 A G 17: 28,642,251 Y820H probably damaging Het
Tas2r115 A G 6: 132,737,467 F174L probably benign Het
Terb1 A C 8: 104,495,114 C185G probably damaging Het
Vmn2r108 A T 17: 20,463,136 V602E probably damaging Het
Vmn2r58 T A 7: 41,865,279 I89F probably damaging Het
Vps13b G T 15: 35,423,245 R237L probably damaging Het
Zfp865 T C 7: 5,031,373 S786P probably benign Het
Other mutations in Clcn3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00782:Clcn3 APN 8 60922792 missense probably damaging 0.99
IGL01088:Clcn3 APN 8 60937347 missense probably damaging 1.00
IGL01449:Clcn3 APN 8 60934598 missense probably damaging 0.97
IGL01792:Clcn3 APN 8 60929322 missense probably damaging 1.00
IGL01845:Clcn3 APN 8 60913095 missense probably benign 0.08
IGL01984:Clcn3 APN 8 60929580 missense probably damaging 1.00
IGL02199:Clcn3 APN 8 60933092 nonsense probably null
IGL02199:Clcn3 APN 8 60927274 missense possibly damaging 0.82
IGL02456:Clcn3 APN 8 60941357 missense probably damaging 1.00
IGL03353:Clcn3 APN 8 60922988 missense probably benign 0.37
R0003:Clcn3 UTSW 8 60927296 nonsense probably null
R0023:Clcn3 UTSW 8 60933070 splice site probably benign
R0023:Clcn3 UTSW 8 60933070 splice site probably benign
R0349:Clcn3 UTSW 8 60941348 missense possibly damaging 0.91
R0437:Clcn3 UTSW 8 60934537 missense possibly damaging 0.69
R0784:Clcn3 UTSW 8 60929203 missense probably benign 0.25
R0840:Clcn3 UTSW 8 60929154 missense probably benign 0.22
R1167:Clcn3 UTSW 8 60922788 critical splice donor site probably null
R2035:Clcn3 UTSW 8 60934598 missense probably damaging 0.97
R2193:Clcn3 UTSW 8 60929187 missense possibly damaging 0.56
R3697:Clcn3 UTSW 8 60913123 missense probably benign 0.02
R3736:Clcn3 UTSW 8 60983652 unclassified probably benign
R4676:Clcn3 UTSW 8 60930651 intron probably benign
R4807:Clcn3 UTSW 8 60934530 missense probably damaging 1.00
R5112:Clcn3 UTSW 8 60954552 missense probably benign 0.07
R5200:Clcn3 UTSW 8 60923005 missense probably damaging 0.99
R5652:Clcn3 UTSW 8 60919353 missense possibly damaging 0.81
R5712:Clcn3 UTSW 8 60937298 critical splice donor site probably null
R5731:Clcn3 UTSW 8 60922889 missense possibly damaging 0.46
R5814:Clcn3 UTSW 8 60934573 missense probably damaging 1.00
R6134:Clcn3 UTSW 8 60934573 missense probably damaging 1.00
R6370:Clcn3 UTSW 8 60923024 missense probably damaging 1.00
R6371:Clcn3 UTSW 8 60937335 missense probably benign 0.06
R6394:Clcn3 UTSW 8 60941291 missense probably damaging 0.99
R6466:Clcn3 UTSW 8 60929561 missense probably damaging 1.00
R6588:Clcn3 UTSW 8 60914827 missense probably benign 0.03
R6750:Clcn3 UTSW 8 60914775 missense possibly damaging 0.93
R7522:Clcn3 UTSW 8 60941412 missense probably benign
R7556:Clcn3 UTSW 8 60929487 missense probably damaging 0.99
R7557:Clcn3 UTSW 8 60937368 missense probably damaging 0.99
R7685:Clcn3 UTSW 8 60933085 missense possibly damaging 0.54
Posted On2014-05-07