Incidental Mutation 'R3895:Twnk'
ID 310520
Institutional Source Beutler Lab
Gene Symbol Twnk
Ensembl Gene ENSMUSG00000025209
Gene Name twinkle mtDNA helicase
Synonyms Peo1, D19Ertd626e, twinkle, Twinl
MMRRC Submission 040806-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R3895 (G1)
Quality Score 225
Status Validated
Chromosome 19
Chromosomal Location 44994102-45001201 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 44995890 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 108 (T108A)
Ref Sequence ENSEMBL: ENSMUSP00000026227 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000026225] [ENSMUST00000026227] [ENSMUST00000097715] [ENSMUST00000130549] [ENSMUST00000179305]
AlphaFold Q8CIW5
Predicted Effect probably benign
Transcript: ENSMUST00000026225
SMART Domains Protein: ENSMUSP00000026225
Gene: ENSMUSG00000025207

DomainStartEndE-ValueType
signal peptide 1 17 N/A INTRINSIC
Sema 56 487 2.38e-165 SMART
PSI 505 556 6.59e-13 SMART
IG 567 649 6.26e-5 SMART
low complexity region 650 666 N/A INTRINSIC
transmembrane domain 677 699 N/A INTRINSIC
low complexity region 701 708 N/A INTRINSIC
low complexity region 713 720 N/A INTRINSIC
low complexity region 734 751 N/A INTRINSIC
low complexity region 761 774 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000026227
AA Change: T108A

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: T108A

DomainStartEndE-ValueType
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: ENSMUST00000097715
SMART Domains Protein: ENSMUSP00000095322
Gene: ENSMUSG00000025208

DomainStartEndE-ValueType
L51_S25_CI-B8 35 108 1.61e-23 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000130549
SMART Domains Protein: ENSMUSP00000138321
Gene: ENSMUSG00000025207

DomainStartEndE-ValueType
signal peptide 1 17 N/A INTRINSIC
Sema 56 487 2.38e-165 SMART
PSI 505 556 6.59e-13 SMART
IG 567 649 6.26e-5 SMART
low complexity region 650 666 N/A INTRINSIC
transmembrane domain 677 699 N/A INTRINSIC
low complexity region 701 708 N/A INTRINSIC
low complexity region 713 720 N/A INTRINSIC
low complexity region 734 751 N/A INTRINSIC
low complexity region 761 774 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000179305
SMART Domains Protein: ENSMUSP00000137395
Gene: ENSMUSG00000025207

DomainStartEndE-ValueType
signal peptide 1 17 N/A INTRINSIC
Sema 56 487 2.38e-165 SMART
PSI 505 556 6.59e-13 SMART
IG 567 649 6.26e-5 SMART
low complexity region 650 666 N/A INTRINSIC
transmembrane domain 677 699 N/A INTRINSIC
low complexity region 701 708 N/A INTRINSIC
low complexity region 713 720 N/A INTRINSIC
low complexity region 734 751 N/A INTRINSIC
low complexity region 761 774 N/A INTRINSIC
Meta Mutation Damage Score 0.1496 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.4%
  • 20x: 95.4%
Validation Efficiency 96% (45/47)
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: 42 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acoxl T C 2: 127,814,445 (GRCm39) probably benign Het
C6 T C 15: 4,837,952 (GRCm39) V854A probably benign Het
Ccnd1 T C 7: 144,491,631 (GRCm39) E136G probably damaging Het
CK137956 A T 4: 127,840,441 (GRCm39) F422I probably benign Het
Csta1 T C 16: 35,951,402 (GRCm39) T7A probably benign Het
Dock8 A G 19: 25,028,865 (GRCm39) E23G probably benign Het
Fbxo8 A T 8: 57,044,556 (GRCm39) R286S probably damaging Het
Gm12258 T G 11: 58,749,375 (GRCm39) Y183* probably null Het
Gvin-ps6 T A 7: 106,022,621 (GRCm39) H127L probably damaging Het
Hectd3 A G 4: 116,853,286 (GRCm39) D171G probably damaging Het
Hoxd11 C T 2: 74,513,136 (GRCm39) R134W probably damaging Het
Ighg2c T C 12: 113,251,278 (GRCm39) T246A unknown Het
Ints6 T C 14: 62,934,060 (GRCm39) I816V probably damaging Het
Lrp4 G A 2: 91,304,294 (GRCm39) G158S probably damaging Het
Mast1 G A 8: 85,662,352 (GRCm39) P52L probably damaging Het
Med13l A G 5: 118,899,388 (GRCm39) D2148G probably null Het
Med24 A G 11: 98,597,214 (GRCm39) S889P probably benign Het
Mgam T A 6: 40,736,054 (GRCm39) M851K probably damaging Het
Mkln1 T A 6: 31,484,602 (GRCm39) L710H probably damaging Het
Morf4l1 A T 9: 89,976,501 (GRCm39) F276I possibly damaging Het
Mslnl G A 17: 25,961,908 (GRCm39) V128M probably damaging Het
Myt1 T A 2: 181,461,863 (GRCm39) S574R probably damaging Het
Nol11 C A 11: 107,059,173 (GRCm39) V644F probably damaging Het
Nusap1 C A 2: 119,458,172 (GRCm39) Q103K possibly damaging Het
Ovgp1 A G 3: 105,893,912 (GRCm39) probably benign Het
Pcdh9 C T 14: 94,124,974 (GRCm39) V399M probably damaging Het
Plekhh1 T C 12: 79,102,006 (GRCm39) S359P probably benign Het
Prg4 G C 1: 150,330,510 (GRCm39) probably benign Het
Ptpn14 C T 1: 189,582,743 (GRCm39) A530V probably benign Het
Rho A G 6: 115,910,863 (GRCm39) Y136C probably damaging Het
Rps3 C T 7: 99,129,103 (GRCm39) R173H probably benign Het
Rufy4 T C 1: 74,186,822 (GRCm39) C537R probably damaging Het
Sall2 T C 14: 52,551,504 (GRCm39) N564D probably damaging Het
Sart3 G A 5: 113,890,488 (GRCm39) R452* probably null Het
Sbf2 T C 7: 110,046,298 (GRCm39) I300V probably damaging Het
Sgo2b A T 8: 64,381,767 (GRCm39) V355E possibly damaging Het
Slc22a5 T C 11: 53,756,651 (GRCm39) K553R possibly damaging Het
Syne1 A G 10: 5,355,456 (GRCm39) V375A probably damaging Het
Trafd1 T C 5: 121,516,804 (GRCm39) E28G probably benign Het
Tsc2 T C 17: 24,818,786 (GRCm39) K1292R probably damaging Het
Unc13c A T 9: 73,840,805 (GRCm39) H15Q probably benign Het
Vps16 T C 2: 130,280,596 (GRCm39) S208P possibly damaging Het
Other mutations in Twnk
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R6595:Twnk UTSW 19 44,998,931 (GRCm39) missense probably damaging 0.99
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'- TTAGAGATGCCAGTGTCGCC -3'
(R):5'- AAACATCACACGAGCTAGCTGG -3'

Sequencing Primer
(F):5'- CGGTGACTACGACTGAAATCCG -3'
(R):5'- TTCCTCAGGGTCTGGAAGCTC -3'
Posted On 2015-04-17