Incidental Mutation '3370:Clca2'
ID68
Institutional Source Beutler Lab
Gene Symbol Clca2
Ensembl Gene ENSMUSG00000036960
Gene Namechloride channel accessory 2
SynonymsClca5
Accession Numbers
Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #3370 of strain dazzle
Quality Score
Status Validated
Chromosome3
Chromosomal Location145070263-145099443 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) C to T at 145077977 bp
ZygosityHomozygous
Amino Acid Change Alanine to Threonine at position 626 (A626T)
Ref Sequence ENSEMBL: ENSMUSP00000143161 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000040465] [ENSMUST00000198993]
Predicted Effect probably damaging
Transcript: ENSMUST00000040465
AA Change: A626T

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000036029
Gene: ENSMUSG00000036960
AA Change: A626T

DomainStartEndE-ValueType
low complexity region 15 29 N/A INTRINSIC
VWA 309 485 3.55e-5 SMART
low complexity region 739 754 N/A INTRINSIC
Blast:FN3 765 875 5e-21 BLAST
Predicted Effect probably damaging
Transcript: ENSMUST00000198993
AA Change: A626T

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000143161
Gene: ENSMUSG00000036960
AA Change: A626T

DomainStartEndE-ValueType
Pfam:CLCA_N 7 265 1.7e-121 PFAM
VWA 309 485 2.2e-7 SMART
Pfam:DUF1973 494 674 7.8e-75 PFAM
Meta Mutation Damage Score 0.2270 question?
Coding Region Coverage
  • 1x: 78.5%
  • 3x: 41.6%
Validation Efficiency 55% (17/31)
MGI Phenotype FUNCTION: This gene encodes a member of the calcium-activated chloride channel regulator (CLCR) family of proteins. Members of this family regulate the transport of chloride across the plasma membrane. Expression of this gene is upregulated by the tumor suppressor protein p53 in response to DNA damage. Mice lacking a functional copy of this gene exhibit increased liver weight and hepatocyte hypertrophy. [provided by RefSeq, Sep 2016]
PHENOTYPE: Mice homozygous for a targeted null mutation exhibit increases in liver weight to body weight ratio and hepatocyte hypertrophy; one incidence of multifocal hepatic necrosis. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 5 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Dido1 A G 2: 180,671,542 M979T probably benign Homo
Mnx1 A G 5: 29,474,887 C241R unknown Homo
Rab38 A G 7: 88,490,651 H176R probably benign Homo
Tap2 A G 17: 34,209,279 probably null Homo
Tmem167 A C 13: 90,098,466 K36N probably damaging Homo
Other mutations in Clca2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00419:Clca2 APN 3 145098813 missense probably damaging 1.00
IGL01337:Clca2 APN 3 145095178 missense probably damaging 1.00
IGL01389:Clca2 APN 3 145077868 critical splice donor site probably null
IGL01595:Clca2 APN 3 145088007 missense probably damaging 1.00
IGL01704:Clca2 APN 3 145095218 missense probably benign 0.04
IGL02416:Clca2 APN 3 145085016 missense probably benign 0.02
IGL02455:Clca2 APN 3 145081411 missense probably benign 0.00
IGL02481:Clca2 APN 3 145084940 missense possibly damaging 0.92
IGL02526:Clca2 APN 3 145088018 missense probably benign 0.02
IGL02797:Clca2 APN 3 145081263 missense probably benign 0.02
IGL03253:Clca2 APN 3 145071563 missense probably benign 0.41
IGL03256:Clca2 APN 3 145086392 missense possibly damaging 0.75
IGL03294:Clca2 APN 3 145097769 missense probably damaging 1.00
R0479:Clca2 UTSW 3 145090849 missense probably damaging 1.00
R0542:Clca2 UTSW 3 145075810 splice site probably benign
R0629:Clca2 UTSW 3 145072239 missense probably benign
R1488:Clca2 UTSW 3 145084164 missense possibly damaging 0.49
R1523:Clca2 UTSW 3 145071644 nonsense probably null
R1568:Clca2 UTSW 3 145075649 nonsense probably null
R1650:Clca2 UTSW 3 145092212 missense probably damaging 1.00
R1771:Clca2 UTSW 3 145081410 missense probably benign 0.12
R2101:Clca2 UTSW 3 145077938 missense probably damaging 0.99
R2242:Clca2 UTSW 3 145090790 missense probably damaging 0.98
R3751:Clca2 UTSW 3 145071455 missense probably benign 0.04
R4496:Clca2 UTSW 3 145092165 missense possibly damaging 0.94
R4962:Clca2 UTSW 3 145077879 missense probably damaging 1.00
R5344:Clca2 UTSW 3 145087942 missense probably damaging 1.00
R5424:Clca2 UTSW 3 145084181 missense probably damaging 0.99
R5931:Clca2 UTSW 3 145092125 missense possibly damaging 0.88
R6181:Clca2 UTSW 3 145090708 nonsense probably null
R6598:Clca2 UTSW 3 145086485 nonsense probably null
R7167:Clca2 UTSW 3 145097784 missense probably benign 0.40
R7229:Clca2 UTSW 3 145084108 missense probably damaging 1.00
R7256:Clca2 UTSW 3 145090847 missense probably damaging 0.99
R7365:Clca2 UTSW 3 145098784 missense probably damaging 1.00
R7813:Clca2 UTSW 3 145084965 missense probably benign 0.26
R8077:Clca2 UTSW 3 145071527 missense possibly damaging 0.56
R8169:Clca2 UTSW 3 145077892 missense probably damaging 1.00
R8290:Clca2 UTSW 3 145087958 missense possibly damaging 0.93
R8300:Clca2 UTSW 3 145098931 missense probably benign 0.00
X0025:Clca2 UTSW 3 145086504 missense possibly damaging 0.87
Z1177:Clca2 UTSW 3 145086451 missense probably damaging 1.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified a G to A transition at position 1953 of the Clca5 transcript in exon 11 of 14 total exons. The mutated nucleotide causes an alanine to threonine substitution at amino acid 626 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Clca5 gene encodes a 942 amino acid protein that is a calcium-activated chloride channel. CLCA5 is a single-pass type I membrane protein, and modulates chloride current across the plasma membrane in a calcium-dependent manner. The protein is highly expressed in eye, spleen, lung, kidney, uterus, and endothelial cells, and weakly expressed in heart and the gastrointestinal tract. CLCA5 plays a role in cell adhesion, and may act as a tumor suppressor in breast and colorectal cancer. The CLCA5 protein contains a von Willebrand factor, type A (VWFA) domain at amino acids 311-483 (Uniprot Q8BG22).  Mice homozygous for a targeted null mutation of Clca5 exhibit increases in liver weight to body weight ratio and hepatocyte hypertrophy.
 
The A626T change occurs in the extracellular region of the protein, and is predicted to be benign by the PolyPhen program.
Posted On2009-12-08