Incidental Mutation 'R7556:Clcn3'
ID 584775
Institutional Source Beutler Lab
Gene Symbol Clcn3
Ensembl Gene ENSMUSG00000004319
Gene Name chloride channel, voltage-sensitive 3
Synonyms Clc3
MMRRC Submission 045624-MU
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.456) question?
Stock # R7556 (G1)
Quality Score 225.009
Status Not validated
Chromosome 8
Chromosomal Location 61363423-61436334 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 61382521 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Serine at position 383 (T383S)
Ref Sequence ENSEMBL: ENSMUSP00000004430 (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: T383S

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000004430
Gene: ENSMUSG00000004319
AA Change: T383S

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: T356S

PolyPhen 2 Score 0.053 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000058648
Gene: ENSMUSG00000004319
AA Change: T356S

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: T325S

PolyPhen 2 Score 0.053 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000091202
Gene: ENSMUSG00000004319
AA Change: T325S

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: T383S

PolyPhen 2 Score 0.053 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000105930
Gene: ENSMUSG00000004319
AA Change: T383S

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: T356S

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000105931
Gene: ENSMUSG00000004319
AA Change: T356S

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.9%
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: 77 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4931429L15Rik C T 9: 46,221,611 (GRCm39) W11* probably null Het
A2ml1 A G 6: 128,546,927 (GRCm39) S401P probably damaging Het
Adamtsl1 T A 4: 86,195,358 (GRCm39) Y592N probably benign Het
Adh6b C T 3: 138,058,546 (GRCm39) T76I probably damaging Het
Aebp2 C A 6: 140,623,137 (GRCm39) P503Q probably benign Het
Ankrd2 A G 19: 42,028,839 (GRCm39) D134G Het
Atf7ip T C 6: 136,538,239 (GRCm39) S491P probably damaging Het
Atp1a3 T C 7: 24,680,991 (GRCm39) D832G probably benign Het
Atrnl1 G A 19: 57,643,278 (GRCm39) V389I probably benign Het
Bahcc1 T C 11: 120,178,589 (GRCm39) S2383P probably damaging Het
Brd9 A G 13: 74,092,886 (GRCm39) D292G possibly damaging Het
Cacna1e G T 1: 154,348,419 (GRCm39) Q781K probably benign Het
Ccdc9 T C 7: 16,018,491 (GRCm39) probably benign Het
Cdc42ep4 C G 11: 113,619,366 (GRCm39) E342Q probably damaging Het
Celf3 C T 3: 94,387,590 (GRCm39) T54M probably damaging Het
Cenpn T C 8: 117,664,008 (GRCm39) Y267H probably damaging Het
Chrnb4 T C 9: 54,942,339 (GRCm39) T312A probably benign Het
Cln3 T C 7: 126,174,242 (GRCm39) Q327R probably damaging Het
Cnep1r1 T C 8: 88,851,761 (GRCm39) L50P probably damaging Het
Cnot6 T C 11: 49,566,144 (GRCm39) N512S probably benign Het
Col7a1 T A 9: 108,811,533 (GRCm39) probably null Het
Cryba4 C T 5: 112,398,969 (GRCm39) R25Q probably damaging Het
Dnah5 A G 15: 28,290,389 (GRCm39) I1260V probably null Het
Dock2 G T 11: 34,611,778 (GRCm39) T195K probably benign Het
Dpp9 A T 17: 56,497,012 (GRCm39) I740N possibly damaging Het
Fbxl21 A T 13: 56,674,741 (GRCm39) N31Y probably benign Het
Frat1 G A 19: 41,818,959 (GRCm39) R118Q possibly damaging Het
Gna11 A G 10: 81,367,208 (GRCm39) F228S Het
Golgb1 A T 16: 36,736,155 (GRCm39) M1842L probably benign Het
Got1 A T 19: 43,491,469 (GRCm39) M327K probably damaging Het
H4c9 A G 13: 22,225,414 (GRCm39) I27T probably damaging Het
Hexa T A 9: 59,470,582 (GRCm39) L468Q probably damaging Het
Ift57 G A 16: 49,526,491 (GRCm39) V178I probably benign Het
Kbtbd13 T C 9: 65,298,757 (GRCm39) T60A probably benign Het
Klk1b5 A G 7: 43,496,649 (GRCm39) T194A probably damaging Het
Krtap16-3 C A 16: 88,759,666 (GRCm39) G16C unknown Het
Lamb3 T C 1: 193,014,757 (GRCm39) S639P probably benign Het
Mapt C A 11: 104,189,528 (GRCm39) P182Q probably benign Het
Mcf2l A G 8: 13,023,071 (GRCm39) T86A probably damaging Het
Mecom G T 3: 30,041,220 (GRCm39) H125N probably benign Het
Med18 T C 4: 132,187,247 (GRCm39) H84R probably benign Het
Muc2 A G 7: 141,307,439 (GRCm39) Y798C Het
Mycbp T C 4: 123,799,060 (GRCm39) Y17H probably damaging Het
Nacad C T 11: 6,551,272 (GRCm39) V640M possibly damaging Het
Ncoa1 C T 12: 4,320,794 (GRCm39) V1092I probably damaging Het
Nomo1 A G 7: 45,715,642 (GRCm39) E696G probably damaging Het
Notch4 G A 17: 34,794,444 (GRCm39) C741Y probably damaging Het
Or10g7 A G 9: 39,905,978 (GRCm39) N291D probably damaging Het
Or6d12 C T 6: 116,493,697 (GRCm39) Q320* probably null Het
Osbpl10 C A 9: 115,036,692 (GRCm39) H229Q probably damaging Het
Pif1 A T 9: 65,496,993 (GRCm39) probably null Het
Plk2 T G 13: 110,533,122 (GRCm39) probably null Het
Ppp1r42 T C 1: 10,065,408 (GRCm39) H172R probably benign Het
Ring1 A G 17: 34,240,688 (GRCm39) I363T possibly damaging Het
Rnf168 T G 16: 32,117,863 (GRCm39) Y475D probably damaging Het
Sbf2 T A 7: 109,913,260 (GRCm39) K1671N probably benign Het
Sema6d A G 2: 124,496,109 (GRCm39) N51S probably damaging Het
Setx C A 2: 29,036,505 (GRCm39) Q997K possibly damaging Het
Skint5 T G 4: 113,425,162 (GRCm39) Q1088P unknown Het
Slc22a27 T C 19: 7,843,119 (GRCm39) D528G probably damaging Het
Slc6a7 T A 18: 61,140,514 (GRCm39) K173* probably null Het
Smc2 T C 4: 52,457,379 (GRCm39) F380L probably benign Het
Spata31d1a T C 13: 59,849,798 (GRCm39) M777V probably benign Het
Stkld1 A T 2: 26,837,307 (GRCm39) N319I possibly damaging Het
Tanc2 T C 11: 105,799,857 (GRCm39) V93A Het
Tbx20 T C 9: 24,661,573 (GRCm39) probably null Het
Trbv20 G A 6: 41,165,715 (GRCm39) V47I probably benign Het
Trip4 A T 9: 65,782,155 (GRCm39) C192* probably null Het
Tsbp1 A T 17: 34,656,691 (GRCm39) I103F unknown Het
Tulp2 A G 7: 45,168,005 (GRCm39) probably null Het
Ush2a C A 1: 188,689,690 (GRCm39) P5084Q probably benign Het
Virma T C 4: 11,518,927 (GRCm39) Y675H probably damaging Het
Vmn2r102 T A 17: 19,898,093 (GRCm39) N369K probably benign Het
Vmn2r59 A T 7: 41,695,233 (GRCm39) M393K probably damaging Het
Vmn2r69 GAAAA GAAAAA 7: 85,060,768 (GRCm39) probably null Het
Xpot A G 10: 121,449,411 (GRCm39) S30P probably benign Het
Zfp947 T C 17: 22,364,597 (GRCm39) Y359C probably benign 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
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
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'- GTTGGGGAAGGCTATCACAG -3'
(R):5'- ATTCAAACTGCAACGAAGCTTG -3'

Sequencing Primer
(F):5'- CACCAGGCAATATTTGCC -3'
(R):5'- CTGCAACGAAGCTTGAGTTAC -3'
Posted On 2019-10-17