Incidental Mutation 'R0014:Clcc1'
ID8179
Institutional Source Beutler Lab
Gene Symbol Clcc1
Ensembl Gene ENSMUSG00000027884
Gene Namechloride channel CLIC-like 1
SynonymsMclc
MMRRC Submission 038309-MU
Accession Numbers

Ncbi RefSeq: NM_001177770.1, NM_145543.2, NM_001177771.1; MGI:2385186

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #R0014 (G1)
Quality Score
Status Validated
Chromosome3
Chromosomal Location108653913-108678840 bp(+) (GRCm38)
Type of Mutationnonsense
DNA Base Change (assembly) T to A at 108661396 bp
ZygosityHeterozygous
Amino Acid Change Cysteine to Stop codon at position 10 (C10*)
Ref Sequence ENSEMBL: ENSMUSP00000118529 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000029483] [ENSMUST00000106609] [ENSMUST00000106613] [ENSMUST00000124384]
Predicted Effect probably null
Transcript: ENSMUST00000029483
AA Change: C10*
SMART Domains Protein: ENSMUSP00000029483
Gene: ENSMUSG00000027884
AA Change: C10*

DomainStartEndE-ValueType
Pfam:MCLC 3 539 2e-266 PFAM
Predicted Effect probably null
Transcript: ENSMUST00000106609
AA Change: C10*
SMART Domains Protein: ENSMUSP00000102220
Gene: ENSMUSG00000027884
AA Change: C10*

DomainStartEndE-ValueType
Pfam:MCLC 3 539 2e-266 PFAM
Predicted Effect probably null
Transcript: ENSMUST00000106613
AA Change: C15*
SMART Domains Protein: ENSMUSP00000102224
Gene: ENSMUSG00000027884
AA Change: C15*

DomainStartEndE-ValueType
Pfam:MCLC 8 544 N/A PFAM
Predicted Effect probably null
Transcript: ENSMUST00000124384
AA Change: C10*
SMART Domains Protein: ENSMUSP00000118529
Gene: ENSMUSG00000027884
AA Change: C10*

DomainStartEndE-ValueType
Pfam:MCLC 3 84 4.2e-37 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000125274
Predicted Effect noncoding transcript
Transcript: ENSMUST00000130352
Predicted Effect noncoding transcript
Transcript: ENSMUST00000139016
Meta Mutation Damage Score 0.9755 question?
Coding Region Coverage
  • 1x: 75.1%
  • 3x: 61.1%
  • 10x: 30.7%
  • 20x: 14.1%
Validation Efficiency 90% (62/69)
MGI Phenotype PHENOTYPE: Mice homozygous for a spontaneous mutation show strain-dependent cerebellar granule cell death and peripheral motor axon degeneration. The peripheral neuropathy, neurogenic muscular atrophy and mild truncal ataxia observed on the C57BL/6J background is not found on the C3H/HeSnJ background. [provided by MGI curators]
Allele List at MGI

All alleles(12) : Targeted(1) Gene trapped(11)

Other mutations in this stock
Total: 33 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
9130409I23Rik T C 1: 181,055,131 F153L possibly damaging Het
Adam17 C T 12: 21,336,644 E445K probably benign Het
Als2 A G 1: 59,211,388 V399A possibly damaging Het
Ankrd52 C A 10: 128,386,452 T583K probably benign Het
Ccr5 T C 9: 124,124,621 F87S probably damaging Het
Cngb3 T C 4: 19,396,685 I346T probably benign Het
Dmbx1 G T 4: 115,918,024 T358K probably damaging Het
Dpyd T C 3: 119,141,935 S670P probably damaging Het
Epc2 A T 2: 49,522,525 K172* probably null Het
Exog T C 9: 119,452,278 I218T probably damaging Het
F2rl2 A T 13: 95,700,909 N154I probably damaging Het
Fbxo30 T A 10: 11,289,859 Y108* probably null Het
Fhad1 A T 4: 141,928,408 L795Q probably damaging Het
Fyttd1 G A 16: 32,905,554 R175Q probably damaging Het
Gbp5 T A 3: 142,506,735 C395S probably damaging Het
Gen1 T C 12: 11,241,641 N716D probably benign Het
Gucy1b1 T C 3: 82,039,861 D347G probably damaging Het
Helz2 A G 2: 181,240,511 L163P probably damaging Het
Hmox2 T A 16: 4,765,033 L210Q probably damaging Het
Khdrbs3 A G 15: 69,024,835 T115A probably benign Het
Lrrk2 T C 15: 91,802,045 probably benign Het
Ncoa6 A C 2: 155,438,043 S18A possibly damaging Het
Neb G A 2: 52,287,156 A1391V probably damaging Het
Nek6 T C 2: 38,558,844 probably benign Het
Pclo C T 5: 14,680,451 probably benign Het
Pex1 G A 5: 3,626,141 probably benign Het
Pi4kb T G 3: 94,998,897 I612S probably damaging Het
Pitx2 T G 3: 129,218,499 S193A possibly damaging Het
Psma8 A G 18: 14,726,530 I86V possibly damaging Het
Slc7a2 T C 8: 40,911,028 L426P probably damaging Het
Tut1 T A 19: 8,962,447 L265Q possibly damaging Het
Wdr63 T C 3: 146,081,423 probably null Het
Zfp458 A G 13: 67,258,090 V95A possibly damaging Het
Other mutations in Clcc1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01443:Clcc1 APN 3 108670903 missense probably benign 0.04
IGL01683:Clcc1 APN 3 108676796 missense probably benign 0.00
IGL02067:Clcc1 APN 3 108668721 missense probably damaging 0.99
IGL02341:Clcc1 APN 3 108673383 missense possibly damaging 0.60
B6584:Clcc1 UTSW 3 108672913 missense probably damaging 1.00
R0733:Clcc1 UTSW 3 108674740 missense probably benign 0.00
R1151:Clcc1 UTSW 3 108668043 missense probably damaging 1.00
R1432:Clcc1 UTSW 3 108668102 missense probably benign 0.11
R3546:Clcc1 UTSW 3 108668113 missense probably benign 0.00
R3547:Clcc1 UTSW 3 108668113 missense probably benign 0.00
R3548:Clcc1 UTSW 3 108668113 missense probably benign 0.00
R3932:Clcc1 UTSW 3 108673366 missense probably damaging 1.00
R4210:Clcc1 UTSW 3 108663591 missense possibly damaging 0.90
R4211:Clcc1 UTSW 3 108663591 missense possibly damaging 0.90
R4756:Clcc1 UTSW 3 108672920 splice site probably null
R4856:Clcc1 UTSW 3 108676838 missense probably benign 0.02
R4886:Clcc1 UTSW 3 108676838 missense probably benign 0.02
R5858:Clcc1 UTSW 3 108661428 missense probably damaging 1.00
R6258:Clcc1 UTSW 3 108673308 missense possibly damaging 0.73
R6301:Clcc1 UTSW 3 108673366 missense probably damaging 1.00
R6414:Clcc1 UTSW 3 108676851 missense possibly damaging 0.90
R6944:Clcc1 UTSW 3 108670968 missense probably damaging 1.00
R6965:Clcc1 UTSW 3 108673309 missense probably damaging 0.99
R7331:Clcc1 UTSW 3 108668078 missense probably damaging 1.00
Nature of Mutation

Multiple transcripts of the Clcc1 gene are displayed on Ensembl and Vega.

Protein Function and Prediction

The Clcc1 gene encodes multiple isoforms of a chloride ion channel. The protein contains three transmembrane domains at amino acids 185-205, 216-236, and 330-350 of the 544 amino acid isoform (Uniprot Q99LI2). Clcc1 (alternatively, Mclc) is a chloride channel in the endoplasmic reticulum, golgi apparatus, and nucleus (1). Chloride channels expressed on intracellular membranes are proposed to regulate the acidification of intracellular compartments as well as vesicle trafficking (2).  Although not studied, it is proposed that Clcc1 functions in spermatogenesis (1).

Expression/Localization

Northern blot analysis of rat tissues identified two splice variants of Clcc1 in the spleen, liver, testis, kidney, heart, aorta, brain, and lung; strong expression was observed in the testis (1).  Strong protein expression was observed in the testis, liver, and lung; within the testis, strong expression was observed in primary spermatocytes (1).

References
Posted On2012-11-20
Science WriterAnne Murray