Incidental Mutation 'R2193:Clcn3'
ID 238268
Institutional Source Beutler Lab
Gene Symbol Clcn3
Ensembl Gene ENSMUSG00000004319
Gene Name chloride channel, voltage-sensitive 3
Synonyms Clc3
MMRRC Submission 040195-MU
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.456) question?
Stock # R2193 (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 A at 61382221 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 456 (I456F)
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: I483F

PolyPhen 2 Score 0.560 (Sensitivity: 0.88; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000004430
Gene: ENSMUSG00000004319
AA Change: I483F

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: I456F

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000058648
Gene: ENSMUSG00000004319
AA Change: I456F

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: I425F

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000091202
Gene: ENSMUSG00000004319
AA Change: I425F

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: I483F

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000105930
Gene: ENSMUSG00000004319
AA Change: I483F

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: I456F

PolyPhen 2 Score 0.560 (Sensitivity: 0.88; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000105931
Gene: ENSMUSG00000004319
AA Change: I456F

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: ENSMUST00000132234
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.8%
  • 10x: 97.6%
  • 20x: 96.1%
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: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acp4 T C 7: 43,902,993 (GRCm39) R289G probably benign Het
Bfar A G 16: 13,515,335 (GRCm39) N183D probably benign Het
Cdca3 A G 6: 124,808,409 (GRCm39) T69A probably damaging Het
Ces1b A T 8: 93,806,505 (GRCm39) C14S probably benign Het
Dab1 C T 4: 104,588,948 (GRCm39) A524V probably benign Het
Dcpp2 A C 17: 24,119,393 (GRCm39) D69A probably damaging Het
Dlgap2 T A 8: 14,793,431 (GRCm39) I475N possibly damaging Het
Dnah6 T A 6: 73,115,623 (GRCm39) M1592L probably damaging Het
Dscaml1 A G 9: 45,596,532 (GRCm39) Q792R probably benign Het
Eif2ak4 A G 2: 118,252,747 (GRCm39) I440V probably benign Het
Frrs1 T C 3: 116,671,994 (GRCm39) S31P probably damaging Het
Isoc2b T C 7: 4,853,823 (GRCm39) H117R probably benign Het
Kalrn C T 16: 33,810,180 (GRCm39) D2525N possibly damaging Het
Klf5 C T 14: 99,536,406 (GRCm39) probably benign Het
Ltn1 G A 16: 87,224,535 (GRCm39) S63F probably damaging Het
Nsf C T 11: 103,821,578 (GRCm39) E26K possibly damaging Het
Oas1f A C 5: 120,989,648 (GRCm39) T196P probably damaging Het
Obscn T C 11: 59,022,472 (GRCm39) R758G possibly damaging Het
Ocln T C 13: 100,676,412 (GRCm39) D27G probably damaging Het
Or2av9 A T 11: 58,380,732 (GRCm39) M283K probably damaging Het
Or2y17 A G 11: 49,231,770 (GRCm39) H137R possibly damaging Het
Rasgrf2 A C 13: 92,160,221 (GRCm39) probably null Het
Sars2 G T 7: 28,448,422 (GRCm39) V268L probably damaging Het
Sin3a T A 9: 57,024,761 (GRCm39) S1040R possibly damaging Het
Vps9d1 A T 8: 123,979,404 (GRCm39) Y39N probably damaging 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
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
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'- AATGGTTTCTCCTGGATTGTTAGCC -3'
(R):5'- AATATTGCCTGGTGTCGTCGAC -3'

Sequencing Primer
(F):5'- GATGCAGCCTCTCGAATCTAG -3'
(R):5'- TGGTGTCGTCGACGCAAG -3'
Posted On 2014-10-02