Mutagenetix > Incidental Mutation

Incidental Mutation '3370:Clca3a2'

Institutional Source

Beutler Lab

Gene Symbol

Clca3a2

Ensembl Gene

ENSMUSG00000028262

Gene Name

chloride channel accessory 3A2

Synonyms

Clca2

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.089) question?

Stock #

3370 of strain dazzle

Quality Score

Status

Validated

Chromosome

Chromosomal Location

144502320-144525255 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 144783738 bp (GRCm39)

Zygosity

Homozygous

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]

AlphaFold

Q9EQR4

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

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

Coding Region Coverage

1x: 78.5%
3x: 41.6%

Validation Efficiency

55% (17/31)

Allele List at MGI

Other mutations in this stock

Total: 5 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Dido1	A	G	2: 180,313,335 (GRCm39)	M979T	probably benign	Homo
Mnx1	A	G	5: 29,679,885 (GRCm39)	C241R	unknown	Homo
Rab38	A	G	7: 88,139,859 (GRCm39)	H176R	probably benign	Homo
Tap2	A	G	17: 34,428,253 (GRCm39)		probably null	Homo
Tmem167	A	C	13: 90,246,585 (GRCm39)	K36N	probably damaging	Homo

Other mutations in Clca3a2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00419:Clca3a2	APN	3	144,804,574 (GRCm39)	missense	probably damaging	1.00
IGL01019:Clca3a2	APN	3	144,519,388 (GRCm39)	nonsense	probably null
IGL01337:Clca3a2	APN	3	144,800,939 (GRCm39)	missense	probably damaging	1.00
IGL01389:Clca3a2	APN	3	144,783,629 (GRCm39)	critical splice donor site	probably null
IGL01595:Clca3a2	APN	3	144,793,768 (GRCm39)	missense	probably damaging	1.00
IGL01663:Clca3a2	APN	3	144,522,916 (GRCm39)	missense	probably damaging	0.97
IGL01704:Clca3a2	APN	3	144,800,979 (GRCm39)	missense	probably benign	0.04
IGL01779:Clca3a2	APN	3	144,525,139 (GRCm39)	missense	possibly damaging	0.47
IGL02066:Clca3a2	APN	3	144,519,216 (GRCm39)	missense	probably benign
IGL02301:Clca3a2	APN	3	144,512,133 (GRCm39)	missense	probably damaging	0.98
IGL02416:Clca3a2	APN	3	144,790,777 (GRCm39)	missense	probably benign	0.02
IGL02455:Clca3a2	APN	3	144,787,172 (GRCm39)	missense	probably benign	0.00
IGL02481:Clca3a2	APN	3	144,790,701 (GRCm39)	missense	possibly damaging	0.92
IGL02526:Clca3a2	APN	3	144,793,779 (GRCm39)	missense	probably benign	0.02
IGL02619:Clca3a2	APN	3	144,512,083 (GRCm39)	missense	probably damaging	1.00
IGL02797:Clca3a2	APN	3	144,787,024 (GRCm39)	missense	probably benign	0.02
IGL02852:Clca3a2	APN	3	144,512,104 (GRCm39)	missense	probably damaging	0.98
IGL02901:Clca3a2	APN	3	144,522,529 (GRCm39)	missense	probably damaging	1.00
IGL03162:Clca3a2	APN	3	144,512,177 (GRCm39)	missense	probably damaging	1.00
IGL03253:Clca3a2	APN	3	144,777,324 (GRCm39)	missense	probably benign	0.41
IGL03256:Clca3a2	APN	3	144,792,153 (GRCm39)	missense	possibly damaging	0.75
IGL03294:Clca3a2	APN	3	144,803,530 (GRCm39)	missense	probably damaging	1.00
R0032:Clca3a2	UTSW	3	144,522,494 (GRCm39)	missense	probably benign	0.01
R0244:Clca3a2	UTSW	3	144,519,659 (GRCm39)	missense	possibly damaging	0.90
R0479:Clca3a2	UTSW	3	144,796,610 (GRCm39)	missense	probably damaging	1.00
R0542:Clca3a2	UTSW	3	144,781,571 (GRCm39)	splice site	probably benign
R0629:Clca3a2	UTSW	3	144,778,000 (GRCm39)	missense	probably benign
R1249:Clca3a2	UTSW	3	144,508,765 (GRCm39)	missense	possibly damaging	0.80
R1370:Clca3a2	UTSW	3	144,519,624 (GRCm39)	splice site	probably benign
R1488:Clca3a2	UTSW	3	144,789,925 (GRCm39)	missense	possibly damaging	0.49
R1523:Clca3a2	UTSW	3	144,777,405 (GRCm39)	nonsense	probably null
R1568:Clca3a2	UTSW	3	144,781,410 (GRCm39)	nonsense	probably null
R1586:Clca3a2	UTSW	3	144,516,477 (GRCm39)	missense	possibly damaging	0.94
R1650:Clca3a2	UTSW	3	144,797,973 (GRCm39)	missense	probably damaging	1.00
R1771:Clca3a2	UTSW	3	144,787,171 (GRCm39)	missense	probably benign	0.12
R1776:Clca3a2	UTSW	3	144,519,681 (GRCm39)	missense	probably damaging	1.00
R1797:Clca3a2	UTSW	3	144,503,398 (GRCm39)	missense	probably benign	0.01
R1869:Clca3a2	UTSW	3	144,512,164 (GRCm39)	missense	probably benign	0.44
R1871:Clca3a2	UTSW	3	144,503,398 (GRCm39)	missense	probably benign	0.01
R1919:Clca3a2	UTSW	3	144,516,457 (GRCm39)	missense	probably benign
R1923:Clca3a2	UTSW	3	144,511,491 (GRCm39)	missense	probably damaging	1.00
R2101:Clca3a2	UTSW	3	144,783,699 (GRCm39)	missense	probably damaging	0.99
R2200:Clca3a2	UTSW	3	144,519,685 (GRCm39)	missense	probably benign	0.10
R2242:Clca3a2	UTSW	3	144,796,551 (GRCm39)	missense	probably damaging	0.98
R2324:Clca3a2	UTSW	3	144,512,041 (GRCm39)	critical splice donor site	probably null
R2937:Clca3a2	UTSW	3	144,519,679 (GRCm39)	missense	probably benign	0.06
R3429:Clca3a2	UTSW	3	144,512,088 (GRCm39)	missense	probably benign	0.07
R3434:Clca3a2	UTSW	3	144,514,522 (GRCm39)	unclassified	probably benign
R3551:Clca3a2	UTSW	3	144,508,842 (GRCm39)	missense	probably damaging	1.00
R3751:Clca3a2	UTSW	3	144,777,216 (GRCm39)	missense	probably benign	0.04
R3952:Clca3a2	UTSW	3	144,508,822 (GRCm39)	missense	probably damaging	1.00
R4120:Clca3a2	UTSW	3	144,516,613 (GRCm39)	missense	probably benign	0.25
R4383:Clca3a2	UTSW	3	144,512,081 (GRCm39)	missense	probably benign	0.02
R4496:Clca3a2	UTSW	3	144,797,926 (GRCm39)	missense	possibly damaging	0.94
R4518:Clca3a2	UTSW	3	144,514,466 (GRCm39)	missense	probably damaging	1.00
R4598:Clca3a2	UTSW	3	144,511,444 (GRCm39)	missense	probably damaging	1.00
R4801:Clca3a2	UTSW	3	144,513,112 (GRCm39)	missense	possibly damaging	0.95
R4802:Clca3a2	UTSW	3	144,513,112 (GRCm39)	missense	possibly damaging	0.95
R4816:Clca3a2	UTSW	3	144,516,613 (GRCm39)	missense	probably benign	0.25
R4934:Clca3a2	UTSW	3	144,523,692 (GRCm39)	missense	probably damaging	1.00
R4942:Clca3a2	UTSW	3	144,512,263 (GRCm39)	missense	probably damaging	1.00
R4962:Clca3a2	UTSW	3	144,783,640 (GRCm39)	missense	probably damaging	1.00
R5123:Clca3a2	UTSW	3	144,512,104 (GRCm39)	missense	probably damaging	1.00
R5156:Clca3a2	UTSW	3	144,511,599 (GRCm39)	missense	probably benign	0.26
R5275:Clca3a2	UTSW	3	144,519,340 (GRCm39)	missense	probably damaging	1.00
R5344:Clca3a2	UTSW	3	144,793,703 (GRCm39)	missense	probably damaging	1.00
R5372:Clca3a2	UTSW	3	144,503,286 (GRCm39)	missense	probably benign	0.00
R5424:Clca3a2	UTSW	3	144,789,942 (GRCm39)	missense	probably damaging	0.99
R5656:Clca3a2	UTSW	3	144,503,393 (GRCm39)	missense	probably benign	0.26
R5931:Clca3a2	UTSW	3	144,797,886 (GRCm39)	missense	possibly damaging	0.88
R6059:Clca3a2	UTSW	3	144,516,531 (GRCm39)	missense	probably damaging	1.00
R6155:Clca3a2	UTSW	3	144,525,118 (GRCm39)	missense	probably damaging	0.99
R6181:Clca3a2	UTSW	3	144,796,469 (GRCm39)	nonsense	probably null
R6254:Clca3a2	UTSW	3	144,507,895 (GRCm39)	missense	probably benign
R6336:Clca3a2	UTSW	3	144,512,239 (GRCm39)	missense	probably benign
R6470:Clca3a2	UTSW	3	144,510,024 (GRCm39)	splice site	probably null
R6593:Clca3a2	UTSW	3	144,514,338 (GRCm39)	critical splice donor site	probably null
R6598:Clca3a2	UTSW	3	144,792,246 (GRCm39)	nonsense	probably null
R6631:Clca3a2	UTSW	3	144,519,405 (GRCm39)	missense	probably benign
R6826:Clca3a2	UTSW	3	144,523,815 (GRCm39)	missense	possibly damaging	0.46
R6836:Clca3a2	UTSW	3	144,512,144 (GRCm39)	missense	probably damaging	0.97
R6896:Clca3a2	UTSW	3	144,514,462 (GRCm39)	missense	probably damaging	1.00
R7167:Clca3a2	UTSW	3	144,803,545 (GRCm39)	missense	probably benign	0.40
R7211:Clca3a2	UTSW	3	144,519,775 (GRCm39)	missense	probably benign	0.00
R7229:Clca3a2	UTSW	3	144,789,869 (GRCm39)	missense	probably damaging	1.00
R7256:Clca3a2	UTSW	3	144,796,608 (GRCm39)	missense	probably damaging	0.99
R7324:Clca3a2	UTSW	3	144,514,372 (GRCm39)	missense	probably damaging	0.99
R7365:Clca3a2	UTSW	3	144,804,545 (GRCm39)	missense	probably damaging	1.00
R7411:Clca3a2	UTSW	3	144,507,860 (GRCm39)	missense	probably damaging	1.00
R7486:Clca3a2	UTSW	3	144,503,362 (GRCm39)	missense	probably damaging	1.00
R7491:Clca3a2	UTSW	3	144,519,340 (GRCm39)	missense	probably damaging	1.00
R7521:Clca3a2	UTSW	3	144,507,674 (GRCm39)	makesense	probably null
R7813:Clca3a2	UTSW	3	144,790,726 (GRCm39)	missense	probably benign	0.26
R7889:Clca3a2	UTSW	3	144,516,574 (GRCm39)	nonsense	probably null
R7946:Clca3a2	UTSW	3	144,513,075 (GRCm39)	critical splice donor site	probably null
R7991:Clca3a2	UTSW	3	144,519,756 (GRCm39)	missense	probably benign	0.00
R8022:Clca3a2	UTSW	3	144,511,527 (GRCm39)	missense	probably damaging	1.00
R8077:Clca3a2	UTSW	3	144,777,288 (GRCm39)	missense	possibly damaging	0.56
R8169:Clca3a2	UTSW	3	144,783,653 (GRCm39)	missense	probably damaging	1.00
R8290:Clca3a2	UTSW	3	144,793,719 (GRCm39)	missense	possibly damaging	0.93
R8300:Clca3a2	UTSW	3	144,804,692 (GRCm39)	missense	probably benign	0.00
R8344:Clca3a2	UTSW	3	144,511,703 (GRCm39)	critical splice acceptor site	probably null
R8350:Clca3a2	UTSW	3	144,783,668 (GRCm39)	missense	probably benign	0.19
R8367:Clca3a2	UTSW	3	144,523,508 (GRCm39)	splice site	probably null
R8371:Clca3a2	UTSW	3	144,513,114 (GRCm39)	nonsense	probably null
R8814:Clca3a2	UTSW	3	144,503,525 (GRCm39)	missense	probably benign	0.18
R8854:Clca3a2	UTSW	3	144,783,852 (GRCm39)	missense	possibly damaging	0.94
R8876:Clca3a2	UTSW	3	144,777,360 (GRCm39)	missense	probably benign	0.00
R8887:Clca3a2	UTSW	3	144,790,810 (GRCm39)	nonsense	probably null
R9006:Clca3a2	UTSW	3	144,783,789 (GRCm39)	missense	probably damaging	0.99
R9031:Clca3a2	UTSW	3	144,511,475 (GRCm39)	missense	probably damaging	1.00
R9069:Clca3a2	UTSW	3	144,519,447 (GRCm39)	splice site	probably benign
R9093:Clca3a2	UTSW	3	144,781,481 (GRCm39)	missense	probably benign	0.20
R9190:Clca3a2	UTSW	3	144,796,599 (GRCm39)	missense	probably benign	0.00
R9201:Clca3a2	UTSW	3	144,519,684 (GRCm39)	missense	probably benign	0.00
R9209:Clca3a2	UTSW	3	144,778,005 (GRCm39)	missense	probably benign	0.00
R9261:Clca3a2	UTSW	3	144,525,158 (GRCm39)	missense	probably benign
R9469:Clca3a2	UTSW	3	144,507,938 (GRCm39)	missense	probably damaging	1.00
R9501:Clca3a2	UTSW	3	144,777,322 (GRCm39)	nonsense	probably null
R9515:Clca3a2	UTSW	3	144,508,808 (GRCm39)	nonsense	probably null
R9569:Clca3a2	UTSW	3	144,513,075 (GRCm39)	critical splice donor site	probably null
R9664:Clca3a2	UTSW	3	144,503,575 (GRCm39)	missense	probably damaging	1.00
X0025:Clca3a2	UTSW	3	144,792,265 (GRCm39)	missense	possibly damaging	0.87
Z1177:Clca3a2	UTSW	3	144,792,212 (GRCm39)	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 On

2009-12-08