Incidental Mutation 'R5200:Clcn3'
ID 400693
Institutional Source Beutler Lab
Gene Symbol Clcn3
Ensembl Gene ENSMUSG00000004319
Gene Name chloride channel, voltage-sensitive 3
Synonyms Clc3
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.456) question?
Stock # R5200 (G1)
Quality Score 225
Status Not validated
Chromosome 8
Chromosomal Location 61363423-61436334 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 61376039 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Arginine at position 618 (K618R)
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 damaging
Transcript: ENSMUST00000004430
AA Change: K645R

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000004430
Gene: ENSMUSG00000004319
AA Change: K645R

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 benign
Transcript: ENSMUST00000056508
AA Change: K618R

PolyPhen 2 Score 0.249 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000058648
Gene: ENSMUSG00000004319
AA Change: K618R

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 benign
Transcript: ENSMUST00000093490
AA Change: K587R

PolyPhen 2 Score 0.249 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000091202
Gene: ENSMUSG00000004319
AA Change: K587R

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 benign
Transcript: ENSMUST00000110301
AA Change: K645R

PolyPhen 2 Score 0.249 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000105930
Gene: ENSMUSG00000004319
AA Change: K645R

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 probably damaging
Transcript: ENSMUST00000110302
AA Change: K618R

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000105931
Gene: ENSMUSG00000004319
AA Change: K618R

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
  • 1x: 99.3%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.5%
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: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Akap9 T C 5: 4,010,734 (GRCm39) V497A probably benign Het
Alx3 T C 3: 107,507,980 (GRCm39) F163S possibly damaging Het
Ankmy1 T C 1: 92,798,014 (GRCm39) R997G probably benign Het
Arfgef2 T C 2: 166,702,604 (GRCm39) S848P probably benign Het
Atp11b A G 3: 35,891,156 (GRCm39) I810V probably benign Het
C1ql4 T G 15: 98,982,718 (GRCm39) I212L probably benign Het
Cep63 T C 9: 102,475,387 (GRCm39) Y443C probably benign Het
Cfap45 C T 1: 172,372,696 (GRCm39) Q464* probably null Het
Dmpk C G 7: 18,821,944 (GRCm39) L301V probably benign Het
Dnaaf4 T C 9: 72,879,713 (GRCm39) S418P probably damaging Het
H2-M10.2 T G 17: 36,595,641 (GRCm39) R216S probably benign Het
Hook1 A G 4: 95,881,367 (GRCm39) D113G probably damaging Het
Ift122 A G 6: 115,897,340 (GRCm39) E914G probably damaging Het
Insr A G 8: 3,248,059 (GRCm39) probably null Het
Itpr2 A T 6: 146,045,605 (GRCm39) probably null Het
Myo6 C T 9: 80,183,656 (GRCm39) Q684* probably null Het
Nrde2 T A 12: 100,096,756 (GRCm39) I1015F possibly damaging Het
Or12e9 T A 2: 87,202,446 (GRCm39) V190E probably damaging Het
Or2d4 G A 7: 106,544,187 (GRCm39) T7I possibly damaging Het
Otx1 C A 11: 21,947,037 (GRCm39) A91S probably damaging Het
Pappa A T 4: 65,074,076 (GRCm39) N210I probably damaging Het
Pax4 G A 6: 28,445,138 (GRCm39) P179L probably damaging Het
Pcx G A 19: 4,668,532 (GRCm39) D656N probably damaging Het
Pms1 T A 1: 53,245,916 (GRCm39) H541L probably benign Het
Pten C T 19: 32,777,291 (GRCm39) P95L probably damaging Het
Rsrc2 G A 5: 123,877,562 (GRCm39) R140* probably null Het
Shc3 T C 13: 51,670,601 (GRCm39) M49V probably damaging Het
Snap91 C G 9: 86,697,497 (GRCm39) K288N probably damaging Het
Spag17 C T 3: 99,970,787 (GRCm39) Q1324* probably null Het
Tasor A G 14: 27,151,183 (GRCm39) E53G probably benign Het
Tfr2 A G 5: 137,569,242 (GRCm39) probably benign Het
Tgfbrap1 A T 1: 43,114,803 (GRCm39) I99K probably damaging Het
Tmem38a T A 8: 73,333,878 (GRCm39) V119E probably damaging Het
Tmtc4 T G 14: 123,182,969 (GRCm39) D243A probably benign Het
Tnc A T 4: 63,889,515 (GRCm39) S1755T probably damaging Het
Trim67 T C 8: 125,551,589 (GRCm39) S590P probably damaging Het
Ttn T A 2: 76,590,287 (GRCm39) T12814S probably damaging Het
Uspl1 T A 5: 149,150,923 (GRCm39) S708T probably benign Het
Vmn2r69 A T 7: 85,055,717 (GRCm39) F807Y probably damaging Het
Vmn2r97 C T 17: 19,148,615 (GRCm39) P170L probably damaging Het
Zfp612 C T 8: 110,816,532 (GRCm39) Q580* probably null Het
Other mutations in Clcn3
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- AGCCGTACCTATTGCAATAGTC -3'
(R):5'- TGGTGTGACAAGAATGACTGTG -3'

Sequencing Primer
(F):5'- CAGGTCTCTTCTGAGGGCAAATC -3'
(R):5'- ACAAGAATGACTGTGTCTCTGG -3'
Posted On 2016-07-06