Incidental Mutation 'P0005:Dars2'
| ID |
7634 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Dars2
|
| Ensembl Gene |
ENSMUSG00000026709 |
| Gene Name |
aspartyl-tRNA synthetase 2 (mitochondrial) |
| Synonyms |
5830468K18Rik |
| MMRRC Submission |
038262-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
P0005 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
1 |
| Chromosomal Location |
160868171-160898228 bp(-) (GRCm39) |
| Type of Mutation |
critical splice donor site (2 bp from exon) |
| DNA Base Change (assembly) |
A to G
at 160881509 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000041851
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000035430]
|
| AlphaFold |
Q8BIP0 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000035430
|
| SMART Domains |
Protein: ENSMUSP00000041851
Gene: ENSMUSG00000026709
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:tRNA_anti-codon
|
65 |
148 |
7e-10 |
PFAM |
|
Pfam:tRNA-synt_2
|
165 |
607 |
1.2e-90 |
PFAM |
|
Pfam:GAD
|
355 |
451 |
2e-13 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000160591
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000160759
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000162654
|
| Meta Mutation Damage Score |
0.9503 |
| Coding Region Coverage |
- 1x: 85.5%
- 3x: 80.5%
- 10x: 66.1%
- 20x: 49.6%
|
| Validation Efficiency |
95% (104/109) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the class-II aminoacyl-tRNA synthetase family. It is a mitochondrial enzyme that specifically aminoacylates aspartyl-tRNA. Mutations in this gene are associated with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). [provided by RefSeq, Nov 2009]
|
| Allele List at MGI |
All alleles(5) : Targeted(2) Gene trapped(3)
|
| Other mutations in this stock |
Total: 20 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Atp13a1 |
T |
C |
8: 70,256,397 (GRCm39) |
V845A |
possibly damaging |
Het |
| Casp6 |
T |
C |
3: 129,705,792 (GRCm39) |
V153A |
probably benign |
Het |
| Col6a1 |
A |
G |
10: 76,553,163 (GRCm39) |
|
probably benign |
Het |
| Hmgcll1 |
T |
A |
9: 75,982,041 (GRCm39) |
M162K |
possibly damaging |
Het |
| Hydin |
A |
T |
8: 111,220,921 (GRCm39) |
|
probably null |
Het |
| Ift74 |
A |
G |
4: 94,550,813 (GRCm39) |
|
probably benign |
Het |
| Itpr1 |
A |
T |
6: 108,358,218 (GRCm39) |
I595F |
probably damaging |
Het |
| Mgat4f |
T |
A |
1: 134,315,646 (GRCm39) |
M15K |
probably benign |
Het |
| Mmp17 |
T |
C |
5: 129,673,695 (GRCm39) |
V258A |
probably benign |
Het |
| Nek6 |
T |
C |
2: 38,459,749 (GRCm39) |
|
probably null |
Het |
| Nomo1 |
A |
T |
7: 45,686,981 (GRCm39) |
|
probably null |
Het |
| Nudt3 |
A |
G |
17: 27,815,689 (GRCm39) |
|
probably benign |
Het |
| Pramel32 |
A |
G |
4: 88,546,187 (GRCm39) |
L385P |
probably damaging |
Het |
| Prkg2 |
A |
C |
5: 99,117,806 (GRCm39) |
F512V |
probably damaging |
Het |
| Ptp4a3 |
T |
A |
15: 73,627,160 (GRCm39) |
D72E |
possibly damaging |
Het |
| Rpgrip1l |
A |
T |
8: 92,025,853 (GRCm39) |
|
probably benign |
Het |
| Rrp9 |
G |
A |
9: 106,358,376 (GRCm39) |
R101H |
probably benign |
Het |
| Slc7a6os |
T |
C |
8: 106,931,154 (GRCm39) |
I161V |
probably benign |
Het |
| Tex15 |
T |
C |
8: 34,060,896 (GRCm39) |
F109L |
probably benign |
Het |
| Tns2 |
A |
G |
15: 102,022,491 (GRCm39) |
Q1188R |
probably damaging |
Het |
|
| Other mutations in Dars2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
R0230:Dars2
|
UTSW |
1 |
160,890,357 (GRCm39) |
missense |
probably benign |
0.02 |
|
R0537:Dars2
|
UTSW |
1 |
160,888,318 (GRCm39) |
missense |
possibly damaging |
0.46 |
|
R0709:Dars2
|
UTSW |
1 |
160,874,498 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1365:Dars2
|
UTSW |
1 |
160,872,564 (GRCm39) |
nonsense |
probably null |
|
|
R1502:Dars2
|
UTSW |
1 |
160,874,375 (GRCm39) |
nonsense |
probably null |
|
|
R1625:Dars2
|
UTSW |
1 |
160,881,614 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R1934:Dars2
|
UTSW |
1 |
160,890,811 (GRCm39) |
splice site |
probably null |
|
|
R2239:Dars2
|
UTSW |
1 |
160,890,852 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R3721:Dars2
|
UTSW |
1 |
160,890,878 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4308:Dars2
|
UTSW |
1 |
160,869,291 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R4786:Dars2
|
UTSW |
1 |
160,888,330 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4859:Dars2
|
UTSW |
1 |
160,872,560 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4903:Dars2
|
UTSW |
1 |
160,878,941 (GRCm39) |
missense |
probably benign |
0.06 |
|
R5042:Dars2
|
UTSW |
1 |
160,872,664 (GRCm39) |
intron |
probably benign |
|
|
R5068:Dars2
|
UTSW |
1 |
160,869,483 (GRCm39) |
missense |
probably benign |
0.02 |
|
R6257:Dars2
|
UTSW |
1 |
160,869,398 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7286:Dars2
|
UTSW |
1 |
160,874,378 (GRCm39) |
missense |
possibly damaging |
0.85 |
|
R7346:Dars2
|
UTSW |
1 |
160,874,342 (GRCm39) |
splice site |
probably null |
|
|
R7444:Dars2
|
UTSW |
1 |
160,874,454 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R7593:Dars2
|
UTSW |
1 |
160,885,113 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7845:Dars2
|
UTSW |
1 |
160,869,318 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8707:Dars2
|
UTSW |
1 |
160,884,081 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8916:Dars2
|
UTSW |
1 |
160,881,552 (GRCm39) |
missense |
probably benign |
0.20 |
|
R9237:Dars2
|
UTSW |
1 |
160,873,025 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9277:Dars2
|
UTSW |
1 |
160,877,527 (GRCm39) |
missense |
probably benign |
0.07 |
|
X0063:Dars2
|
UTSW |
1 |
160,884,063 (GRCm39) |
missense |
probably benign |
0.14 |
|
| Background |
Heterozygous mutations in DARS2 leads to leukoencephalopathy with brainstem and spinal cord involvement and lacatae elevation (LBSL; OMIM #611105; (1;2)). LPSL patients develop progressive cerebellar ataxia, spasticity, dorsal column dysfunction, and often a mild cognifitive deficit or decline (3).
|
| References |
1. Isohanni, P., Linnankivi, T., Buzkova, J., Lonnqvist, T., Pihko, H., Valanne, L., Tienari, P. J., Elovaara, I., Pirttila, T., Reunanen, M., Koivisto, K., Marjavaara, S., and Suomalainen, A. (2010) DARS2 Mutations in Mitochondrial Leucoencephalopathy and Multiple Sclerosis. J Med Genet. 47, 66-70.
2. Scheper, G. C., van der Klok, T., van Andel, R. J., van Berkel, C. G., Sissler, M., Smet, J., Muravina, T. I., Serkov, S. V., Uziel, G., Bugiani, M., Schiffmann, R., Krageloh-Mann, I., Smeitink, J. A., Florentz, C., Van Coster, R., Pronk, J. C., and van der Knaap, M. S. (2007) Mitochondrial Aspartyl-tRNA Synthetase Deficiency Causes Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation. Nat Genet. 39, 534-539.
3. Yamashita, S., Miyake, N., Matsumoto, N., Osaka, H., Iai, M., Aida, N., and Tanaka, Y. (2012) Neuropathology of Leukoencephalopathy with Brainstem and Spinal Cord Involvement and High Lactate Caused by a Homozygous Mutation of DARS2. |
| Posted On |
2012-10-05 |
| Science Writer |
Anne Murray |
Incidental Mutation