Incidental Mutation 'R3605:Tk2'
| ID |
269053 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Tk2
|
| Ensembl Gene |
ENSMUSG00000035824 |
| Gene Name |
thymidine kinase 2, mitochondrial |
| Synonyms |
|
| MMRRC Submission |
040670-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.755)
|
| Stock # |
R3605 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
8 |
| Chromosomal Location |
104953317-104975190 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 104957803 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Alanine
at position 181
(V181A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000148642
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000050211]
[ENSMUST00000211995]
[ENSMUST00000212209]
[ENSMUST00000212275]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000050211
AA Change: V181A
PolyPhen 2
Score 0.946 (Sensitivity: 0.80; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000053616
Gene: ENSMUSG00000035824
AA Change: V181A
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
2 |
35 |
N/A |
INTRINSIC |
|
Pfam:dNK
|
58 |
267 |
1.2e-67 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000211995
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000212165
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000212209
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000212275
AA Change: V181A
PolyPhen 2
Score 0.946 (Sensitivity: 0.80; Specificity: 0.95)
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000212805
|
| Meta Mutation Damage Score |
0.4981 |
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.5%
- 10x: 96.8%
- 20x: 93.3%
|
| Validation Efficiency |
95% (40/42) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a deoxyribonucleoside kinase that specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. The encoded enzyme localizes to the mitochondria and is required for mitochondrial DNA synthesis. Mutations in this gene are associated with a myopathic form of mitochondrial DNA depletion syndrome. Alternate splicing results in multiple transcript variants encoding distinct isoforms, some of which lack transit peptide, so are not localized to mitochondria. [provided by RefSeq, Dec 2012]
PHENOTYPE: Knock-out mice die at 2-4 wks of age showing stunted growth, hypothermia, progressive mtDNA loss, aberrant myocardial fibers and altered adipose tissue structure. Knock-in mutant mice show encephalomyelopathy, impaired gait, mtDNA loss, altered mt dNTP pools and respiratory chain enzyme activities. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 39 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Ankrd35 |
C |
T |
3: 96,589,497 (GRCm39) |
Q239* |
probably null |
Het |
| Arid4b |
T |
C |
13: 14,294,826 (GRCm39) |
V36A |
probably damaging |
Het |
| Art2b |
T |
A |
7: 101,229,152 (GRCm39) |
N249I |
probably benign |
Het |
| Bpifb1 |
T |
A |
2: 154,053,485 (GRCm39) |
N242K |
possibly damaging |
Het |
| Cd200r1 |
A |
G |
16: 44,609,939 (GRCm39) |
T53A |
possibly damaging |
Het |
| Cracr2b |
C |
T |
7: 141,046,059 (GRCm39) |
P370S |
possibly damaging |
Het |
| Crb1 |
T |
A |
1: 139,165,077 (GRCm39) |
T1016S |
probably damaging |
Het |
| Esrrg |
A |
G |
1: 187,943,299 (GRCm39) |
H424R |
possibly damaging |
Het |
| Fgfrl1 |
C |
A |
5: 108,853,289 (GRCm39) |
T213K |
probably damaging |
Het |
| Flrt3 |
T |
A |
2: 140,503,287 (GRCm39) |
N114Y |
probably damaging |
Het |
| Fsip2 |
T |
C |
2: 82,815,253 (GRCm39) |
V3662A |
probably benign |
Het |
| Gabra6 |
T |
A |
11: 42,205,777 (GRCm39) |
I359F |
probably benign |
Het |
| Gal |
A |
G |
19: 3,464,026 (GRCm39) |
|
probably null |
Het |
| Gm10801 |
G |
C |
2: 98,494,352 (GRCm39) |
R143T |
possibly damaging |
Het |
| Gm5814 |
G |
T |
17: 47,721,430 (GRCm39) |
R48L |
probably damaging |
Het |
| Hcn1 |
G |
A |
13: 118,111,788 (GRCm39) |
G584D |
unknown |
Het |
| Iqgap1 |
T |
C |
7: 80,373,537 (GRCm39) |
D1484G |
probably benign |
Het |
| Kmt2a |
G |
A |
9: 44,760,493 (GRCm39) |
T485M |
probably damaging |
Het |
| Kprp |
C |
A |
3: 92,731,588 (GRCm39) |
Q487H |
unknown |
Het |
| Lctl |
T |
C |
9: 64,040,475 (GRCm39) |
Y473H |
probably damaging |
Het |
| Lrrc8d |
G |
A |
5: 105,974,873 (GRCm39) |
C93Y |
unknown |
Het |
| Mnt |
T |
A |
11: 74,727,746 (GRCm39) |
S211T |
possibly damaging |
Het |
| Mtdh |
T |
A |
15: 34,114,258 (GRCm39) |
|
probably benign |
Het |
| Nxt1 |
T |
C |
2: 148,517,399 (GRCm39) |
W47R |
probably damaging |
Het |
| Or4f59 |
T |
A |
2: 111,873,168 (GRCm39) |
I70F |
probably benign |
Het |
| Or5k3 |
T |
C |
16: 58,969,846 (GRCm39) |
I211T |
probably damaging |
Het |
| Plekha7 |
T |
C |
7: 115,763,477 (GRCm39) |
D313G |
possibly damaging |
Het |
| Ranbp10 |
A |
G |
8: 106,502,667 (GRCm39) |
S300P |
probably benign |
Het |
| Rbl1 |
A |
T |
2: 157,019,153 (GRCm39) |
F531I |
probably damaging |
Het |
| Rpap2 |
A |
G |
5: 107,768,395 (GRCm39) |
D411G |
probably damaging |
Het |
| Sapcd1 |
A |
G |
17: 35,246,781 (GRCm39) |
F36L |
probably damaging |
Het |
| Svep1 |
A |
T |
4: 58,066,542 (GRCm39) |
S3181T |
probably benign |
Het |
| Tgfbr2 |
G |
A |
9: 115,938,960 (GRCm39) |
T314I |
probably benign |
Het |
| Thbs4 |
G |
T |
13: 92,894,467 (GRCm39) |
C685* |
probably null |
Het |
| Traf2 |
T |
C |
2: 25,420,427 (GRCm39) |
T141A |
probably benign |
Het |
| Ttn |
C |
T |
2: 76,661,788 (GRCm39) |
|
probably null |
Het |
| Ube3c |
A |
G |
5: 29,803,936 (GRCm39) |
T180A |
possibly damaging |
Het |
| Yif1b |
C |
T |
7: 28,937,835 (GRCm39) |
A7V |
possibly damaging |
Het |
| Zfp738 |
A |
T |
13: 67,819,508 (GRCm39) |
L151* |
probably null |
Het |
|
| Other mutations in Tk2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02447:Tk2
|
APN |
8 |
104,967,770 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02525:Tk2
|
APN |
8 |
104,970,032 (GRCm39) |
missense |
probably benign |
0.02 |
|
IGL03211:Tk2
|
APN |
8 |
104,970,073 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0333:Tk2
|
UTSW |
8 |
104,975,146 (GRCm39) |
unclassified |
probably benign |
|
|
R0691:Tk2
|
UTSW |
8 |
104,957,824 (GRCm39) |
missense |
probably benign |
0.16 |
|
R1851:Tk2
|
UTSW |
8 |
104,975,077 (GRCm39) |
nonsense |
probably null |
|
|
R3508:Tk2
|
UTSW |
8 |
104,957,825 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4161:Tk2
|
UTSW |
8 |
104,965,465 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5328:Tk2
|
UTSW |
8 |
104,955,931 (GRCm39) |
splice site |
probably null |
|
|
R5546:Tk2
|
UTSW |
8 |
104,974,315 (GRCm39) |
missense |
possibly damaging |
0.51 |
|
R6909:Tk2
|
UTSW |
8 |
104,963,442 (GRCm39) |
nonsense |
probably null |
|
|
R8098:Tk2
|
UTSW |
8 |
104,957,804 (GRCm39) |
missense |
probably benign |
0.05 |
|
R8354:Tk2
|
UTSW |
8 |
104,967,746 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8357:Tk2
|
UTSW |
8 |
104,963,450 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8454:Tk2
|
UTSW |
8 |
104,967,746 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8457:Tk2
|
UTSW |
8 |
104,963,450 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8978:Tk2
|
UTSW |
8 |
104,957,809 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
| Predicted Primers |
PCR Primer
(F):5'- TCCTTCATGGACAGAAGAACC -3'
(R):5'- TGTGGGCATCATCTGTGGAC -3'
Sequencing Primer
(F):5'- GAACCCCCTAAATGCTGCCTG -3'
(R):5'- ACACTATGCAACATGCTCTTGGTG -3'
|
| Posted On |
2015-02-19 |
Incidental Mutation