Mutagenetix > Incidental Mutation

Incidental Mutation 'F5493:Cars1'

563

Institutional Source

Beutler Lab

Gene Symbol

Cars1

Ensembl Gene

ENSMUSG00000010755

Gene Name

cysteinyl-tRNA synthetase 1

Synonyms

Cars, CA3

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

F5493 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

143110967-143153827 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 143123608 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Serine at position 448 (T448S)

Ref Sequence

ENSEMBL: ENSMUSP00000101529 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000010899] [ENSMUST00000105909]

AlphaFold

Q9ER72

Predicted Effect

probably damaging
Transcript: ENSMUST00000010899
AA Change: T531S

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000010899
Gene: ENSMUSG00000010755
AA Change: T531S

Domain	Start	End	E-Value	Type
Pfam:tRNA-synt_1e	124	537	2.7e-128	PFAM
Blast:DALR_2	584	644	2e-13	BLAST
coiled coil region	728	768	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000105909
AA Change: T448S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000101529
Gene: ENSMUSG00000010755
AA Change: T448S

Domain	Start	End	E-Value	Type
Pfam:tRNA-synt_1e	41	454	2e-129	PFAM
Pfam:tRNA-synt_1g	387	465	1.2e-6	PFAM
Blast:DALR_2	501	561	1e-13	BLAST
coiled coil region	645	685	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000134753

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135032

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146462

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146904

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184553

Predicted Effect

probably benign
Transcript: ENSMUST00000208575

Meta Mutation Damage Score

0.1518

Coding Region Coverage

1x: 76.6%
3x: 51.4%

Het Detection Efficiency

27.8%

Validation Efficiency

67% (74/111)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. This gene is one of several located near the imprinted gene domain on chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2010]

Allele List at MGI

All alleles(37) : Targeted, other(2) Gene trapped(35)

Other mutations in this stock

Total: 10 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Cdca2	T	A	14: 67,915,141 (GRCm39)	N706I	probably damaging	Het
Fat1	A	G	8: 45,478,517 (GRCm39)	E2521G	probably damaging	Het
Fmo2	C	A	1: 162,708,101 (GRCm39)	V345L	probably benign	Het
Frrs1l	T	C	4: 56,968,293 (GRCm39)	M160V	probably benign	Het
Nckap5	A	T	1: 125,953,564 (GRCm39)	M996K	probably benign	Het
Nlrp4d	A	T	7: 10,115,011 (GRCm39)	D568E	possibly damaging	Het
Pex1	T	G	5: 3,685,912 (GRCm39)		probably null	Het
Ptprd	A	G	4: 76,002,645 (GRCm39)	L17P	probably damaging	Het
Tnfsf13b	T	A	8: 10,056,916 (GRCm39)	V25E	probably damaging	Het
Zfp386	T	C	12: 116,023,922 (GRCm39)	Y512H	probably damaging	Het

Other mutations in Cars1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01155:Cars1	APN	7	143,123,586 (GRCm39)	missense	probably benign	0.03
IGL02192:Cars1	APN	7	143,125,325 (GRCm39)	missense	probably damaging	1.00
IGL02645:Cars1	APN	7	143,111,646 (GRCm39)	missense	probably damaging	0.97
IGL02807:Cars1	APN	7	143,123,209 (GRCm39)	missense	possibly damaging	0.87
IGL02860:Cars1	APN	7	143,140,158 (GRCm39)	missense	probably damaging	1.00
IGL03005:Cars1	APN	7	143,112,906 (GRCm39)	missense	probably damaging	1.00
Vroom	UTSW	7	143,124,385 (GRCm39)	missense	probably damaging	1.00
Zoom	UTSW	7	143,146,362 (GRCm39)	nonsense	probably null
BB001:Cars1	UTSW	7	143,123,608 (GRCm39)	missense	possibly damaging	0.88
BB011:Cars1	UTSW	7	143,123,608 (GRCm39)	missense	possibly damaging	0.88
R0358:Cars1	UTSW	7	143,142,219 (GRCm39)	splice site	probably benign
R0452:Cars1	UTSW	7	143,146,362 (GRCm39)	nonsense	probably null
R0717:Cars1	UTSW	7	143,138,492 (GRCm39)	missense	probably damaging	0.98
R0930:Cars1	UTSW	7	143,124,307 (GRCm39)	missense	probably damaging	1.00
R1069:Cars1	UTSW	7	143,123,844 (GRCm39)	missense	probably benign	0.40
R1184:Cars1	UTSW	7	143,140,876 (GRCm39)	missense	probably damaging	1.00
R1503:Cars1	UTSW	7	143,122,726 (GRCm39)	missense	probably benign	0.04
R1755:Cars1	UTSW	7	143,123,194 (GRCm39)	missense	probably damaging	1.00
R1762:Cars1	UTSW	7	143,146,211 (GRCm39)	missense	probably damaging	1.00
R1783:Cars1	UTSW	7	143,146,211 (GRCm39)	missense	probably damaging	1.00
R1786:Cars1	UTSW	7	143,146,211 (GRCm39)	missense	probably damaging	1.00
R1828:Cars1	UTSW	7	143,130,385 (GRCm39)	missense	probably damaging	0.97
R2084:Cars1	UTSW	7	143,140,919 (GRCm39)	missense	probably benign	0.03
R2132:Cars1	UTSW	7	143,146,211 (GRCm39)	missense	probably damaging	1.00
R2133:Cars1	UTSW	7	143,146,211 (GRCm39)	missense	probably damaging	1.00
R2397:Cars1	UTSW	7	143,146,244 (GRCm39)	missense	possibly damaging	0.61
R4012:Cars1	UTSW	7	143,113,411 (GRCm39)	missense	possibly damaging	0.65
R4057:Cars1	UTSW	7	143,124,385 (GRCm39)	missense	probably damaging	1.00
R4082:Cars1	UTSW	7	143,123,234 (GRCm39)	missense	probably damaging	1.00
R4118:Cars1	UTSW	7	143,113,384 (GRCm39)	critical splice donor site	probably null
R4527:Cars1	UTSW	7	143,118,786 (GRCm39)	missense	probably benign	0.22
R4663:Cars1	UTSW	7	143,129,697 (GRCm39)	missense	probably damaging	1.00
R4758:Cars1	UTSW	7	143,125,304 (GRCm39)	missense	probably benign	0.01
R4820:Cars1	UTSW	7	143,124,301 (GRCm39)	missense	probably damaging	1.00
R4921:Cars1	UTSW	7	143,123,212 (GRCm39)	missense	probably damaging	1.00
R4923:Cars1	UTSW	7	143,123,587 (GRCm39)	missense	probably damaging	0.97
R5512:Cars1	UTSW	7	143,123,870 (GRCm39)	missense	possibly damaging	0.91
R6505:Cars1	UTSW	7	143,118,744 (GRCm39)	missense	probably damaging	1.00
R7125:Cars1	UTSW	7	143,138,510 (GRCm39)	missense	probably benign	0.01
R7641:Cars1	UTSW	7	143,140,840 (GRCm39)	critical splice donor site	probably null
R7674:Cars1	UTSW	7	143,140,840 (GRCm39)	critical splice donor site	probably null
R7812:Cars1	UTSW	7	143,123,784 (GRCm39)	missense	probably damaging	1.00
R7924:Cars1	UTSW	7	143,123,608 (GRCm39)	missense	possibly damaging	0.88
R8260:Cars1	UTSW	7	143,139,446 (GRCm39)	missense	probably benign
R8447:Cars1	UTSW	7	143,123,766 (GRCm39)	missense	possibly damaging	0.67
R8905:Cars1	UTSW	7	143,140,196 (GRCm39)	missense	probably damaging	1.00
R9200:Cars1	UTSW	7	143,129,654 (GRCm39)	critical splice donor site	probably null
R9240:Cars1	UTSW	7	143,138,533 (GRCm39)	missense	probably benign	0.01
R9441:Cars1	UTSW	7	143,123,185 (GRCm39)	missense	probably benign	0.00
R9566:Cars1	UTSW	7	143,113,384 (GRCm39)	critical splice donor site	probably null
R9603:Cars1	UTSW	7	143,112,929 (GRCm39)	missense	possibly damaging	0.83
X0021:Cars1	UTSW	7	143,130,321 (GRCm39)	critical splice donor site	probably null

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to T transversion at position 1628 of the Cars transcript in exon 14 of 23 total exons. Multiple transcripts of the Cars gene are displayed on Ensembl and Vega. The mutated nucleotide causes a threonine to serine substitution at amino acid 531 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (see related file).

Protein Function and Prediction

The Cars gene encodes the 831 amino acid cytoplasmic cysteinyl-tRNA synthetase. This enzyme belongs to the class-I aminoacyl-tRNA synthetase family. Two isoforms are produced by alternative splicing. The important catalytic HIGH and KMSKS motifs occur at residues 140-150 and 489-493, respectively (Uniprot Q9ER72).

The T531S change is predicted to be benign by the PolyPhen program.

Posted On

2010-11-29