Incidental Mutation 'R1470:Twnk'
ID 198027
Institutional Source Beutler Lab
Gene Symbol Twnk
Ensembl Gene ENSMUSG00000025209
Gene Name twinkle mtDNA helicase
Synonyms Peo1, D19Ertd626e, twinkle, Twinl
MMRRC Submission 039523-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1470 (G1)
Quality Score 225
Status Validated
Chromosome 19
Chromosomal Location 44994102-45001201 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 44997820 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Methionine at position 450 (V450M)
Ref Sequence ENSEMBL: ENSMUSP00000026227 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000026227] [ENSMUST00000097715]
AlphaFold Q8CIW5
Predicted Effect probably damaging
Transcript: ENSMUST00000026227
AA Change: V450M

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: V450M

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
Meta Mutation Damage Score 0.2953 question?
Coding Region Coverage
  • 1x: 97.5%
  • 3x: 97.0%
  • 10x: 95.5%
  • 20x: 93.0%
Validation Efficiency 97% (125/129)
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: 142 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aak1 T A 6: 86,944,337 (GRCm39) S749T unknown Het
Abcb4 A T 5: 8,990,968 (GRCm39) I843F probably damaging Het
Abcb6 A T 1: 75,149,323 (GRCm39) probably benign Het
AC238840.1 A T 7: 38,467,377 (GRCm39) noncoding transcript Het
Actr8 T A 14: 29,708,926 (GRCm39) H244Q possibly damaging Het
Acyp2 A G 11: 30,456,452 (GRCm39) probably benign Het
Adgrv1 A G 13: 81,530,417 (GRCm39) Y5886H probably benign Het
Afap1 C T 5: 36,119,081 (GRCm39) probably benign Het
Agk T A 6: 40,363,751 (GRCm39) W244R probably damaging Het
Akirin1 T A 4: 123,631,883 (GRCm39) probably benign Het
Ankrd11 C A 8: 123,626,463 (GRCm39) V161L probably damaging Het
Arap3 T C 18: 38,122,249 (GRCm39) probably null Het
Arhgap29 A G 3: 121,785,968 (GRCm39) probably benign Het
Armc3 A G 2: 19,243,547 (GRCm39) M88V probably benign Het
Atp13a5 G T 16: 29,167,833 (GRCm39) P109T probably benign Het
Avpr1b T A 1: 131,528,323 (GRCm39) V282D probably damaging Het
Baz2b T C 2: 59,808,890 (GRCm39) K120E possibly damaging Het
Bltp1 T C 3: 37,052,480 (GRCm39) M3060T probably benign Het
Cacna1a T A 8: 85,241,579 (GRCm39) probably benign Het
Cacng6 G A 7: 3,473,404 (GRCm39) C76Y probably damaging Het
Cactin G T 10: 81,158,985 (GRCm39) E279* probably null Het
Car9 A G 4: 43,510,222 (GRCm39) Y268C probably damaging Het
Ccdc146 T A 5: 21,524,564 (GRCm39) I263F probably damaging Het
Cdc16 A T 8: 13,808,992 (GRCm39) probably benign Het
Cdh16 T G 8: 105,345,003 (GRCm39) S429R probably benign Het
Cep250 A G 2: 155,832,995 (GRCm39) E1639G probably damaging Het
Ces1d A T 8: 93,921,649 (GRCm39) V38D possibly damaging Het
Chd1 A T 17: 15,946,545 (GRCm39) Q97L possibly damaging Het
Ciita G A 16: 10,332,332 (GRCm39) D898N possibly damaging Het
Clstn1 A G 4: 149,719,179 (GRCm39) N336S possibly damaging Het
Cntnap5a A G 1: 116,187,249 (GRCm39) D607G probably damaging Het
Col1a2 G A 6: 4,518,822 (GRCm39) probably benign Het
Col20a1 C T 2: 180,636,753 (GRCm39) H245Y probably benign Het
Coq8b A T 7: 26,951,734 (GRCm39) T399S probably benign Het
Cpn2 A G 16: 30,079,003 (GRCm39) S233P probably benign Het
Cryz G A 3: 154,312,113 (GRCm39) G70D probably damaging Het
Csmd1 G T 8: 16,207,218 (GRCm39) probably benign Het
Def6 T A 17: 28,444,956 (GRCm39) D451E possibly damaging Het
Dnah8 T A 17: 30,966,251 (GRCm39) C2480* probably null Het
Dnah9 T C 11: 65,818,648 (GRCm39) N3230S probably benign Het
Dyrk4 G T 6: 126,893,337 (GRCm39) S15* probably null Het
Erc1 T C 6: 119,671,563 (GRCm39) R917G probably damaging Het
Fgd2 T A 17: 29,593,082 (GRCm39) probably benign Het
Frem3 G T 8: 81,337,820 (GRCm39) V38L probably benign Het
Gas2l3 T C 10: 89,249,796 (GRCm39) I441V probably benign Het
Gm14393 T A 2: 174,905,774 (GRCm39) Y6F probably damaging Het
Gm1527 A G 3: 28,969,417 (GRCm39) K256E possibly damaging Het
Gm21905 G T 5: 68,103,740 (GRCm39) probably benign Het
Gtf2ird1 T A 5: 134,424,656 (GRCm39) probably null Het
Hmces C A 6: 87,913,121 (GRCm39) T292K probably benign Het
Hpse2 G A 19: 43,376,692 (GRCm39) S20L probably benign Het
Ift70b G T 2: 75,768,155 (GRCm39) S199R probably benign Het
Ikbke A T 1: 131,204,224 (GRCm39) V23E probably null Het
Ino80 A T 2: 119,210,130 (GRCm39) V1387E probably damaging Het
Islr G T 9: 58,064,589 (GRCm39) A306D probably damaging Het
Jakmip1 G A 5: 37,258,182 (GRCm39) G276D probably damaging Het
Jchain A G 5: 88,673,979 (GRCm39) V55A probably benign Het
Kalrn T C 16: 34,007,841 (GRCm39) K1350E probably damaging Het
Kansl1l T C 1: 66,841,156 (GRCm39) Q48R possibly damaging Het
Kmt5a T C 5: 124,585,334 (GRCm39) L23P probably damaging Het
Lrba C T 3: 86,644,449 (GRCm39) H381Y probably damaging Het
Lrch3 T C 16: 32,808,865 (GRCm39) probably benign Het
Lrrc32 T C 7: 98,148,564 (GRCm39) V448A probably benign Het
Mapkbp1 T C 2: 119,848,301 (GRCm39) M617T probably damaging Het
Megf6 C T 4: 154,336,876 (GRCm39) probably benign Het
Mfap1a T C 2: 121,333,282 (GRCm39) M50V probably benign Het
Mgam G T 6: 40,736,062 (GRCm39) A854S probably damaging Het
Myh3 A C 11: 66,988,885 (GRCm39) probably benign Het
Myo18b C A 5: 112,840,899 (GRCm39) R2298L probably damaging Het
Myo1h T A 5: 114,457,765 (GRCm39) M92K probably damaging Het
Nfkbib T C 7: 28,461,447 (GRCm39) probably null Het
Nlrp2 T A 7: 5,303,950 (GRCm39) T192S probably benign Het
Nr2f1 A T 13: 78,346,284 (GRCm39) Y137N possibly damaging Het
Nup98 T A 7: 101,796,513 (GRCm39) D841V probably damaging Het
Nvl A G 1: 180,966,827 (GRCm39) V59A probably damaging Het
Ogdhl C A 14: 32,068,745 (GRCm39) N948K probably damaging Het
Or11g27 T C 14: 50,771,159 (GRCm39) S97P possibly damaging Het
Or12j3 A G 7: 139,953,026 (GRCm39) S166P probably benign Het
Or13a24 A G 7: 140,154,662 (GRCm39) T199A probably benign Het
Or51g1 A C 7: 102,633,530 (GRCm39) Y280* probably null Het
Orc2 A C 1: 58,520,317 (GRCm39) probably benign Het
Osgin1 G A 8: 120,171,704 (GRCm39) R166H probably damaging Het
Palb2 A T 7: 121,706,746 (GRCm39) F741I probably benign Het
Palb2 G T 7: 121,706,747 (GRCm39) Y740* probably null Het
Parvb G A 15: 84,155,453 (GRCm39) G46D probably damaging Het
Parvb G A 15: 84,155,509 (GRCm39) D65N probably benign Het
Pcsk2 A T 2: 143,388,438 (GRCm39) K10* probably null Het
Pde3a C T 6: 141,411,932 (GRCm39) A502V probably benign Het
Pfas T C 11: 68,882,185 (GRCm39) I893V probably benign Het
Pla2g4a A T 1: 149,716,471 (GRCm39) D663E probably damaging Het
Prickle2 G A 6: 92,435,583 (GRCm39) P6L probably damaging Het
Prx T A 7: 27,217,026 (GRCm39) M648K probably benign Het
Ptpn21 T C 12: 98,654,735 (GRCm39) N744S probably benign Het
Ptprq C T 10: 107,554,435 (GRCm39) V97M probably damaging Het
Pvr T C 7: 19,652,549 (GRCm39) E122G possibly damaging Het
Racgap1 T C 15: 99,537,656 (GRCm39) K15E probably damaging Het
Rock1 C T 18: 10,136,091 (GRCm39) probably null Het
Rorc T A 3: 94,304,609 (GRCm39) Y331* probably null Het
Rpl37 T C 15: 5,148,096 (GRCm39) V91A probably benign Het
Rrp36 T A 17: 46,983,306 (GRCm39) K103* probably null Het
Ryr3 T A 2: 112,483,352 (GRCm39) M4142L probably benign Het
Sash1 A T 10: 8,665,357 (GRCm39) L125H probably damaging Het
Scn5a T C 9: 119,365,541 (GRCm39) M369V possibly damaging Het
Siglec1 A T 2: 130,912,307 (GRCm39) N1678K probably benign Het
Slc15a5 A T 6: 138,049,992 (GRCm39) V141E probably benign Het
Slc43a1 T C 2: 84,690,020 (GRCm39) probably benign Het
Slc8a3 A T 12: 81,246,484 (GRCm39) H856Q probably benign Het
Spmip11 T C 15: 98,483,142 (GRCm39) probably benign Het
Sptlc2 T A 12: 87,402,414 (GRCm39) M171L probably benign Het
Srcap T A 7: 127,158,899 (GRCm39) probably benign Het
St6gal2 A G 17: 55,797,944 (GRCm39) D310G probably damaging Het
Susd2 T A 10: 75,473,888 (GRCm39) D689V probably damaging Het
Suz12 A T 11: 79,910,558 (GRCm39) E303V possibly damaging Het
Taldo1 C A 7: 140,978,500 (GRCm39) T150K probably damaging Het
Tex14 T C 11: 87,440,355 (GRCm39) probably benign Het
Tg T A 15: 66,721,312 (GRCm39) F274I possibly damaging Het
Tmem151b T C 17: 45,856,663 (GRCm39) D259G probably damaging Het
Tmem179 G T 12: 112,468,288 (GRCm39) H64Q probably benign Het
Tmem236 A G 2: 14,223,732 (GRCm39) T174A probably benign Het
Tmtc1 T A 6: 148,207,483 (GRCm39) probably benign Het
Tnc A T 4: 63,884,811 (GRCm39) N1821K probably damaging Het
Tnfrsf11a A G 1: 105,752,773 (GRCm39) N261S probably damaging Het
Traf6 G T 2: 101,526,994 (GRCm39) probably benign Het
Trank1 C A 9: 111,172,300 (GRCm39) F96L possibly damaging Het
Trim56 T A 5: 137,142,017 (GRCm39) I500F probably damaging Het
Ttll5 A G 12: 85,926,168 (GRCm39) I321V possibly damaging Het
Ttn C A 2: 76,608,367 (GRCm39) W17852L probably damaging Het
Uba52 A G 8: 70,962,206 (GRCm39) I127T possibly damaging Het
Ubr4 T A 4: 139,148,537 (GRCm39) probably null Het
Uggt1 A T 1: 36,215,877 (GRCm39) M130K probably benign Het
Ulk4 T A 9: 120,910,722 (GRCm39) T1101S probably benign Het
Urb1 A G 16: 90,548,902 (GRCm39) S2269P probably benign Het
Ush2a G T 1: 188,132,403 (GRCm39) R875L probably benign Het
Usp9y T A Y: 1,332,471 (GRCm39) H1624L probably benign Homo
Vipr1 T C 9: 121,494,586 (GRCm39) L308S possibly damaging Het
Vps50 G A 6: 3,517,777 (GRCm39) probably benign Het
Xdh T G 17: 74,198,107 (GRCm39) K1260T probably damaging Het
Yipf4 A G 17: 74,800,963 (GRCm39) I94V probably benign Het
Zfhx4 A G 3: 5,478,206 (GRCm39) *3582W probably null Het
Zfp58 T C 13: 67,640,144 (GRCm39) N116D possibly damaging Het
Zfp750 C A 11: 121,402,819 (GRCm39) R643L probably benign Het
Znfx1 A G 2: 166,884,507 (GRCm39) V51A 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
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'- CCCCTCTCAACTTTGACTGGAATCTTGG -3'
(R):5'- AGGGTCTTACCTGATGCTCTGTTGTCC -3'

Sequencing Primer
(F):5'- acaccagaagagagcatcag -3'
(R):5'- CCGTGGAAAGTCATGAAGTAGAG -3'
Posted On 2014-05-23