Incidental Mutation 'R6595:Twnk'
| ID |
524901 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Twnk
|
| Ensembl Gene |
ENSMUSG00000025209 |
| Gene Name |
twinkle mtDNA helicase |
| Synonyms |
Peo1, D19Ertd626e, twinkle, Twinl |
| MMRRC Submission |
044719-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R6595 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
19 |
| Chromosomal Location |
44994102-45001201 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 44998931 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Alanine
at position 557
(V557A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000026227
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000026227]
[ENSMUST00000039016]
[ENSMUST00000097715]
[ENSMUST00000179108]
|
| AlphaFold |
Q8CIW5 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000026227
AA Change: V557A
PolyPhen 2
Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: V557A
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
213 |
224 |
N/A |
INTRINSIC |
|
Blast:TOPRIM
|
260 |
331 |
8e-16 |
BLAST |
|
Pfam:AAA_25
|
377 |
565 |
5.6e-25 |
PFAM |
|
Pfam:DnaB_C
|
390 |
631 |
6.7e-17 |
PFAM |
|
Pfam:KaiC
|
394 |
628 |
2.6e-11 |
PFAM |
|
low complexity region
|
650 |
661 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000039016
|
| SMART Domains |
Protein: ENSMUSP00000045478
Gene: ENSMUSG00000035342
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
99 |
105 |
N/A |
INTRINSIC |
|
low complexity region
|
187 |
199 |
N/A |
INTRINSIC |
|
low complexity region
|
242 |
265 |
N/A |
INTRINSIC |
|
low complexity region
|
267 |
321 |
N/A |
INTRINSIC |
|
low complexity region
|
375 |
407 |
N/A |
INTRINSIC |
|
low complexity region
|
412 |
423 |
N/A |
INTRINSIC |
|
Pfam:Fez1
|
441 |
639 |
4.2e-82 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000097715
|
| SMART Domains |
Protein: ENSMUSP00000095322
Gene: ENSMUSG00000025208
| Domain | Start | End | E-Value | Type |
|---|
|
L51_S25_CI-B8
|
35 |
108 |
1.61e-23 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000179108
|
| SMART Domains |
Protein: ENSMUSP00000137571
Gene: ENSMUSG00000035342
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
99 |
105 |
N/A |
INTRINSIC |
|
low complexity region
|
187 |
199 |
N/A |
INTRINSIC |
|
low complexity region
|
242 |
265 |
N/A |
INTRINSIC |
|
low complexity region
|
267 |
321 |
N/A |
INTRINSIC |
|
low complexity region
|
375 |
407 |
N/A |
INTRINSIC |
|
low complexity region
|
412 |
423 |
N/A |
INTRINSIC |
|
Pfam:Fez1
|
441 |
639 |
4.2e-82 |
PFAM |
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.6%
- 10x: 98.2%
- 20x: 94.5%
|
| Validation Efficiency |
97% (37/38) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Aug 2009]
PHENOTYPE: Homozygous embryos display abnormal development. Embryos die around E8.5. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 38 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca15 |
A |
T |
7: 119,993,710 (GRCm39) |
Y1310F |
probably benign |
Het |
| Ankrd54 |
A |
G |
15: 78,942,185 (GRCm39) |
F148L |
probably damaging |
Het |
| Bag4 |
C |
T |
8: 26,259,528 (GRCm39) |
D224N |
probably damaging |
Het |
| Bhlhe40 |
TG |
TGG |
6: 108,641,818 (GRCm39) |
254 |
probably null |
Het |
| Camk2b |
A |
T |
11: 5,942,856 (GRCm39) |
H126Q |
probably damaging |
Het |
| Camsap3 |
G |
T |
8: 3,654,186 (GRCm39) |
V608L |
probably damaging |
Het |
| Camsap3 |
A |
T |
8: 3,658,742 (GRCm39) |
M796L |
probably damaging |
Het |
| Cdh19 |
T |
C |
1: 110,853,517 (GRCm39) |
D308G |
probably benign |
Het |
| Cfap299 |
A |
T |
5: 98,949,717 (GRCm39) |
D217V |
possibly damaging |
Het |
| Cpsf1 |
T |
C |
15: 76,486,710 (GRCm39) |
I275M |
probably damaging |
Het |
| Cuta |
A |
G |
17: 27,157,856 (GRCm39) |
|
probably null |
Het |
| Dclk2 |
A |
G |
3: 86,699,374 (GRCm39) |
|
probably benign |
Het |
| Dst |
T |
G |
1: 34,289,761 (GRCm39) |
L784R |
probably damaging |
Het |
| Fbn1 |
T |
C |
2: 125,184,750 (GRCm39) |
M1681V |
possibly damaging |
Het |
| Fbxo9 |
A |
T |
9: 77,994,494 (GRCm39) |
D274E |
probably damaging |
Het |
| Frem2 |
T |
A |
3: 53,457,205 (GRCm39) |
D2049V |
probably damaging |
Het |
| Fscn3 |
T |
C |
6: 28,430,174 (GRCm39) |
Y115H |
probably damaging |
Het |
| Glp2r |
G |
T |
11: 67,655,603 (GRCm39) |
D46E |
probably benign |
Het |
| Gpat2 |
G |
C |
2: 127,273,838 (GRCm39) |
G294R |
possibly damaging |
Het |
| Irx5 |
A |
G |
8: 93,086,247 (GRCm39) |
Y110C |
probably damaging |
Het |
| Kdm5d |
T |
C |
Y: 939,829 (GRCm39) |
S994P |
probably benign |
Homo |
| Klhl2 |
A |
T |
8: 65,196,077 (GRCm39) |
C555* |
probably null |
Het |
| Krtap4-7 |
A |
T |
11: 99,534,560 (GRCm39) |
I101N |
unknown |
Het |
| Or13a27 |
A |
G |
7: 139,925,560 (GRCm39) |
L114P |
probably damaging |
Het |
| Or4f57 |
A |
T |
2: 111,790,515 (GRCm39) |
V301E |
possibly damaging |
Het |
| Pcdhb21 |
T |
C |
18: 37,648,961 (GRCm39) |
S697P |
probably damaging |
Het |
| Pramel27 |
T |
C |
4: 143,579,326 (GRCm39) |
C304R |
probably damaging |
Het |
| Rasgrf2 |
A |
T |
13: 92,167,361 (GRCm39) |
H237Q |
probably damaging |
Het |
| Rnf216 |
A |
T |
5: 143,076,412 (GRCm39) |
D157E |
probably benign |
Het |
| Rxrg |
T |
A |
1: 167,454,905 (GRCm39) |
F163I |
probably damaging |
Het |
| Soat2 |
T |
A |
15: 102,069,028 (GRCm39) |
I351N |
probably damaging |
Het |
| Srp72 |
C |
T |
5: 77,132,047 (GRCm39) |
T242I |
probably benign |
Het |
| Svopl |
T |
C |
6: 38,018,002 (GRCm39) |
|
probably null |
Het |
| Tbc1d2b |
G |
A |
9: 90,108,145 (GRCm39) |
P469S |
probably benign |
Het |
| Tbkbp1 |
G |
A |
11: 97,029,578 (GRCm39) |
|
probably benign |
Het |
| Tecta |
A |
G |
9: 42,295,523 (GRCm39) |
V324A |
probably damaging |
Het |
| Vmn2r18 |
G |
A |
5: 151,485,889 (GRCm39) |
T535I |
probably damaging |
Het |
| Zc3h14 |
T |
A |
12: 98,723,285 (GRCm39) |
S85T |
probably damaging |
Het |
|
| Other mutations in Twnk |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00858:Twnk
|
APN |
19 |
44,996,065 (GRCm39) |
missense |
probably benign |
0.03 |
|
IGL01367:Twnk
|
APN |
19 |
45,000,090 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
IGL01736:Twnk
|
APN |
19 |
44,998,627 (GRCm39) |
missense |
probably damaging |
0.97 |
|
IGL02724:Twnk
|
APN |
19 |
44,996,557 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL03368:Twnk
|
APN |
19 |
44,998,931 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0121:Twnk
|
UTSW |
19 |
44,997,704 (GRCm39) |
unclassified |
probably benign |
|
|
R0389:Twnk
|
UTSW |
19 |
44,996,578 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R0427:Twnk
|
UTSW |
19 |
44,996,026 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0443:Twnk
|
UTSW |
19 |
44,996,578 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R0501:Twnk
|
UTSW |
19 |
44,996,185 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0791:Twnk
|
UTSW |
19 |
44,998,693 (GRCm39) |
unclassified |
probably benign |
|
|
R1193:Twnk
|
UTSW |
19 |
44,996,229 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1470:Twnk
|
UTSW |
19 |
44,997,820 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1470:Twnk
|
UTSW |
19 |
44,997,820 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1487:Twnk
|
UTSW |
19 |
44,996,815 (GRCm39) |
critical splice donor site |
probably null |
|
|
R1556:Twnk
|
UTSW |
19 |
44,997,850 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R3895:Twnk
|
UTSW |
19 |
44,995,890 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R5652:Twnk
|
UTSW |
19 |
44,995,732 (GRCm39) |
missense |
possibly damaging |
0.85 |
|
R6373:Twnk
|
UTSW |
19 |
44,997,820 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6880:Twnk
|
UTSW |
19 |
44,995,855 (GRCm39) |
missense |
probably benign |
|
|
R7349:Twnk
|
UTSW |
19 |
44,998,600 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R7401:Twnk
|
UTSW |
19 |
45,000,219 (GRCm39) |
missense |
probably benign |
0.15 |
|
R7417:Twnk
|
UTSW |
19 |
44,999,003 (GRCm39) |
splice site |
probably null |
|
|
R7798:Twnk
|
UTSW |
19 |
44,996,107 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7994:Twnk
|
UTSW |
19 |
44,996,277 (GRCm39) |
missense |
probably benign |
0.03 |
|
R8698:Twnk
|
UTSW |
19 |
44,996,299 (GRCm39) |
missense |
probably benign |
|
|
R8826:Twnk
|
UTSW |
19 |
44,996,434 (GRCm39) |
missense |
probably benign |
|
|
R8855:Twnk
|
UTSW |
19 |
45,000,272 (GRCm39) |
nonsense |
probably null |
|
|
R8866:Twnk
|
UTSW |
19 |
45,000,272 (GRCm39) |
nonsense |
probably null |
|
|
R8972:Twnk
|
UTSW |
19 |
45,000,149 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9683:Twnk
|
UTSW |
19 |
44,998,622 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- CTTAGGTAGCGAGTGTAATGGC -3'
(R):5'- ATCCTAGGCCTCAAGGAACC -3'
Sequencing Primer
(F):5'- CGAGTGTAATGGCTGGGAC -3'
(R):5'- GGTATCCCTCACCCATGGC -3'
|
| Posted On |
2018-06-22 |
Incidental Mutation