Incidental Mutation 'R6880:Twnk'
ID 536645
Institutional Source Beutler Lab
Gene Symbol Twnk
Ensembl Gene ENSMUSG00000025209
Gene Name twinkle mtDNA helicase
Synonyms Peo1, D19Ertd626e, twinkle, Twinl
MMRRC Submission 044976-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6880 (G1)
Quality Score 225.009
Status Validated
Chromosome 19
Chromosomal Location 44994102-45001201 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 44995855 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 96 (D96G)
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 benign
Transcript: ENSMUST00000026227
AA Change: D96G

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: D96G

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: 100.0%
  • 3x: 99.9%
  • 10x: 99.4%
  • 20x: 98.1%
Validation Efficiency 97% (62/64)
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: 63 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acad9 T A 3: 36,123,854 (GRCm39) probably null Het
Aff3 T C 1: 38,574,243 (GRCm39) H206R probably damaging Het
Aff3 T C 1: 38,666,209 (GRCm39) D5G possibly damaging Het
Alg5 A G 3: 54,646,264 (GRCm39) E43G probably damaging Het
Ankrd36 T C 11: 5,578,748 (GRCm39) L4P probably damaging Het
Ano1 T C 7: 144,198,479 (GRCm39) Y345C probably benign Het
Atf7ip A G 6: 136,538,038 (GRCm39) I432V probably damaging Het
B230307C23Rik T C 16: 97,798,627 (GRCm39) probably benign Het
Baz2b T A 2: 59,743,283 (GRCm39) N1563Y probably damaging Het
Bhlha15 A T 5: 144,128,451 (GRCm39) T188S probably damaging Het
Cbr3 T C 16: 93,487,426 (GRCm39) V203A probably benign Het
Cpsf1 T C 15: 76,486,739 (GRCm39) T266A probably benign Het
Dnah7c T C 1: 46,566,831 (GRCm39) Y681H probably damaging Het
Dock2 C T 11: 34,579,279 (GRCm39) probably null Het
Dsc1 T A 18: 20,221,429 (GRCm39) D682V probably damaging Het
Fkbp15 A T 4: 62,254,732 (GRCm39) I256N possibly damaging Het
Foxd1 A C 13: 98,491,225 (GRCm39) D33A unknown Het
Gid4 T A 11: 60,327,261 (GRCm39) F149I probably damaging Het
Hmcn2 G T 2: 31,233,068 (GRCm39) V206L probably damaging Het
Ighg2b T C 12: 113,270,726 (GRCm39) I135V Het
Ighv1-24 T C 12: 114,736,663 (GRCm39) Y79C possibly damaging Het
Impg1 T A 9: 80,312,082 (GRCm39) D167V probably damaging Het
Jakmip1 T C 5: 37,262,967 (GRCm39) S372P possibly damaging Het
Kcnb1 T C 2: 166,947,727 (GRCm39) T374A probably damaging Het
Lrrn4 A G 2: 132,714,032 (GRCm39) S305P probably damaging Het
Ltbp1 C T 17: 75,628,044 (GRCm39) T1179I possibly damaging Het
Mab21l2 A G 3: 86,454,463 (GRCm39) I179T possibly damaging Het
Myo5b A T 18: 74,855,501 (GRCm39) H1230L probably benign Het
Myocos T C 1: 162,484,602 (GRCm39) probably null Het
Nipa2 T C 7: 55,582,999 (GRCm39) T249A probably damaging Het
Oas1a C A 5: 121,040,003 (GRCm39) R196L probably damaging Het
Or2ag18 A T 7: 106,405,019 (GRCm39) S217T probably damaging Het
Or5an11 A G 19: 12,245,974 (GRCm39) I127V probably benign Het
Or8k41 A G 2: 86,314,069 (GRCm39) F6L probably benign Het
Phxr2 G A 10: 98,961,946 (GRCm39) probably benign Het
Pigq A G 17: 26,153,802 (GRCm39) L85P probably damaging Het
Pla2g4a T A 1: 149,727,202 (GRCm39) D518V possibly damaging Het
Pm20d1 A G 1: 131,731,839 (GRCm39) K294E probably benign Het
Polr3d C A 14: 70,677,455 (GRCm39) R307L probably benign Het
Pou5f2 T C 13: 78,173,613 (GRCm39) L185P possibly damaging Het
Prex2 A T 1: 11,202,608 (GRCm39) N506Y probably damaging Het
Proser1 T A 3: 53,385,260 (GRCm39) S381T probably benign Het
Prpf4b T C 13: 35,078,436 (GRCm39) V682A possibly damaging Het
Prr14l A T 5: 32,988,211 (GRCm39) L428Q probably benign Het
Prss23 A G 7: 89,160,033 (GRCm39) V12A probably benign Het
Qki T C 17: 10,434,376 (GRCm39) D321G probably benign Het
Rab11fip5 A G 6: 85,325,827 (GRCm39) L193P probably damaging Het
Retreg1 T G 15: 25,971,825 (GRCm39) L245R probably damaging Het
Rfc1 T C 5: 65,434,729 (GRCm39) N679S probably benign Het
Rpl4 C T 9: 64,084,335 (GRCm39) A220V probably damaging Het
Rxra G A 2: 27,638,668 (GRCm39) E224K possibly damaging Het
Slc26a7 A G 4: 14,516,159 (GRCm39) C557R possibly damaging Het
Sncaip A G 18: 53,002,136 (GRCm39) K219R probably damaging Het
Sorbs1 G C 19: 40,365,244 (GRCm39) R180G probably benign Het
Sphkap A G 1: 83,234,978 (GRCm39) V1616A probably damaging Het
Sulf1 T C 1: 12,912,979 (GRCm39) C738R probably damaging Het
Suz12 T A 11: 79,892,998 (GRCm39) C38* probably null Het
Ttn T C 2: 76,550,842 (GRCm39) T23190A probably damaging Het
Vcan T A 13: 89,860,500 (GRCm39) N289I probably damaging Het
Vmn2r120 A T 17: 57,816,187 (GRCm39) S723T probably damaging Het
Vmn2r97 A T 17: 19,134,770 (GRCm39) I63F probably benign Het
Washc5 T C 15: 59,222,021 (GRCm39) N125S probably benign Het
Zfp865 A G 7: 5,033,548 (GRCm39) Y511C probably 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
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
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'- ATGTGGCTTCTTCTCCGACG -3'
(R):5'- CGGTTCCAGATCCTCAAGAC -3'

Sequencing Primer
(F):5'- GATCTTGCTGCCACTGCGTG -3'
(R):5'- GTTCCAGATCCTCAAGACCTCCTC -3'
Posted On 2018-10-18