Incidental Mutation 'R1193:Twnk'
ID 100967
Institutional Source Beutler Lab
Gene Symbol Twnk
Ensembl Gene ENSMUSG00000025209
Gene Name twinkle mtDNA helicase
Synonyms Peo1, D19Ertd626e, twinkle, Twinl
MMRRC Submission 039265-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1193 (G1)
Quality Score 225
Status Not validated
Chromosome 19
Chromosomal Location 44994102-45001201 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 44996229 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Glutamic Acid at position 221 (K221E)
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: K221E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: K221E

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
Coding Region Coverage
  • 1x: 98.9%
  • 3x: 97.8%
  • 10x: 94.5%
  • 20x: 86.3%
Validation Efficiency
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: 20 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Actl6a A G 3: 32,766,293 (GRCm39) D49G probably benign Het
D6Ertd527e C G 6: 87,088,506 (GRCm39) T223S unknown Het
Dna2 C T 10: 62,784,966 (GRCm39) R28W probably benign Het
Gpm6a A T 8: 55,500,268 (GRCm39) probably null Het
Nrbp1 T A 5: 31,403,157 (GRCm39) I210N probably damaging Het
Nudt5 G A 2: 5,868,411 (GRCm39) S103N probably benign Het
Or5an9 A T 19: 12,187,803 (GRCm39) Y291F probably damaging Het
Or6z3 A G 7: 6,463,715 (GRCm39) N69S probably benign Het
Pds5a G T 5: 65,795,145 (GRCm39) A697E probably damaging Het
Pik3ca A G 3: 32,510,242 (GRCm39) D806G probably damaging Het
Rars1 C T 11: 35,700,153 (GRCm39) A548T possibly damaging Het
Rfk C T 19: 17,372,685 (GRCm39) P69L probably damaging Het
Shf G A 2: 122,199,163 (GRCm39) P51S probably damaging Het
Sp4 C T 12: 118,262,981 (GRCm39) R355H possibly damaging Het
Tcaim T C 9: 122,647,895 (GRCm39) Y137H probably damaging Het
Tenm2 C T 11: 35,954,004 (GRCm39) G1236R possibly damaging Het
Tmem150c T C 5: 100,231,451 (GRCm39) T175A probably damaging Het
Vmn2r67 T C 7: 84,800,653 (GRCm39) K428E probably damaging Het
Vmn2r82 T A 10: 79,213,739 (GRCm39) Y108* probably null Het
Wwox G A 8: 115,406,614 (GRCm39) V202M probably benign 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
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
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'- TGAGGATCTGGAACCGAGCCATAC -3'
(R):5'- ACACAATCCGACGGAACTGTTCAAG -3'

Sequencing Primer
(F):5'- AGCCATACCTCTTTGGGAGC -3'
(R):5'- GGTAAGCAGACTGTCCCTC -3'
Posted On 2014-01-15