Mutagenetix > Incidental Mutation

Incidental Mutation 'R7349:Twnk'

570465

Institutional Source

Beutler Lab

Gene Symbol

Twnk

Ensembl Gene

ENSMUSG00000025209

Gene Name

twinkle mtDNA helicase

Synonyms

Peo1, D19Ertd626e, twinkle, Twinl

MMRRC Submission

045435-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7349 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

44994102-45001201 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 44998600 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 506 (V506A)

Ref Sequence

ENSEMBL: ENSMUSP00000026227 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000026227] [ENSMUST00000097715]

AlphaFold

Q8CIW5

Predicted Effect

possibly damaging
Transcript: ENSMUST00000026227
AA Change: V506A

PolyPhen 2 Score 0.652 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: V506A

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: ENSMUST00000097715

SMART Domains

Protein: ENSMUSP00000095322
Gene: ENSMUSG00000025208

Domain	Start	End	E-Value	Type
L51_S25_CI-B8	35	108	1.61e-23	SMART

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.9%

Validation Efficiency

100% (70/70)

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: 70 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930486L24Rik	T	A	13: 60,990,717 (GRCm39)	T326S	possibly damaging	Het
Acly	A	T	11: 100,412,817 (GRCm39)	H91Q	probably benign	Het
Acp3	T	A	9: 104,168,657 (GRCm39)	I403F	probably benign	Het
Angpt2	T	A	8: 18,742,090 (GRCm39)	M489L	probably damaging	Het
Arap1	T	C	7: 101,039,435 (GRCm39)	I565T	possibly damaging	Het
Atg16l2	T	C	7: 100,939,473 (GRCm39)	D563G	probably damaging	Het
Atp6v0a2	T	A	5: 124,789,392 (GRCm39)	Y386*	probably null	Het
Atp8b4	A	G	2: 126,167,265 (GRCm39)	V1078A	probably benign	Het
Bsn	T	C	9: 107,987,982 (GRCm39)	D2590G	unknown	Het
Casp12	T	C	9: 5,345,527 (GRCm39)		probably null	Het
Ccdc87	T	C	19: 4,891,868 (GRCm39)	S787P	probably damaging	Het
Cdh13	A	G	8: 119,969,097 (GRCm39)	T485A	probably damaging	Het
Cstdc5	A	G	16: 36,184,674 (GRCm39)	V23A	probably damaging	Het
Dip2a	T	C	10: 76,121,426 (GRCm39)	H810R	probably damaging	Het
Dmbt1	A	T	7: 130,642,854 (GRCm39)	Y120F	unknown	Het
Dmgdh	C	T	13: 93,888,741 (GRCm39)	T793I	possibly damaging	Het
Dnhd1	A	G	7: 105,359,330 (GRCm39)	D3555G	probably damaging	Het
Eif4e1b	T	C	13: 54,932,006 (GRCm39)	V30A	probably benign	Het
Ercc5	T	G	1: 44,220,068 (GRCm39)	D1113E	possibly damaging	Het
Fbn1	T	C	2: 125,157,321 (GRCm39)	N2321D	possibly damaging	Het
Fbrs	T	C	7: 127,081,971 (GRCm39)	L237P	probably damaging	Het
Flg2	T	A	3: 93,127,513 (GRCm39)	S2142T	unknown	Het
Ftsj3	G	A	11: 106,140,572 (GRCm39)	T761I	probably damaging	Het
Gdi2	C	A	13: 3,606,395 (GRCm39)	T157N	probably benign	Het
Gm8122	C	A	14: 43,088,058 (GRCm39)		probably null	Het
Gtpbp10	T	C	5: 5,605,379 (GRCm39)	E108G	possibly damaging	Het
Hectd4	T	C	5: 121,448,726 (GRCm39)	L358P	probably damaging	Het
Herc3	T	C	6: 58,835,971 (GRCm39)	C271R	probably benign	Het
Hspb1	C	T	5: 135,918,187 (GRCm39)	T178M	possibly damaging	Het
Htr3b	C	T	9: 48,847,319 (GRCm39)	V399M	probably benign	Het
Hydin	A	G	8: 111,124,803 (GRCm39)		probably null	Het
Itpr3	T	A	17: 27,326,786 (GRCm39)		probably null	Het
Iyd	G	T	10: 3,495,638 (GRCm39)	V99F	possibly damaging	Het
Lrrc36	G	A	8: 106,178,900 (GRCm39)	G365D	probably damaging	Het
Map1b	T	A	13: 99,570,148 (GRCm39)	I858F	unknown	Het
Med12l	A	T	3: 59,165,746 (GRCm39)	D1488V	probably damaging	Het
Ms4a6c	T	A	19: 11,455,555 (GRCm39)	N121K	probably damaging	Het
Nlrp1b	T	G	11: 71,072,943 (GRCm39)	Q300P	probably benign	Het
Nlrp3	G	A	11: 59,438,912 (GRCm39)	R163H	probably damaging	Het
Nr4a3	T	G	4: 48,051,290 (GRCm39)	S15A	possibly damaging	Het
Optc	T	G	1: 133,825,617 (GRCm39)	D356A	probably damaging	Het
Or52h7	A	G	7: 104,213,857 (GRCm39)	H143R	probably benign	Het
Or9s15	T	C	1: 92,524,904 (GRCm39)	V221A	possibly damaging	Het
Pdzd2	C	G	15: 12,399,291 (GRCm39)	V812L	probably damaging	Het
Phlpp2	T	C	8: 110,655,278 (GRCm39)	F691S	probably damaging	Het
Pigk	T	C	3: 152,453,238 (GRCm39)	F319L	probably benign	Het
Pkhd1l1	A	G	15: 44,378,350 (GRCm39)	T1035A	probably damaging	Het
Plekhg3	A	G	12: 76,611,339 (GRCm39)	T261A	probably benign	Het
Plekhm1	A	G	11: 103,278,160 (GRCm39)	F312S	probably damaging	Het
Pms2	T	A	5: 143,862,654 (GRCm39)	I587N	probably benign	Het
Ppl	T	A	16: 4,922,593 (GRCm39)	H272L	probably damaging	Het
Prkce	G	A	17: 86,800,783 (GRCm39)	A400T	probably benign	Het
Ptpn9	T	C	9: 56,951,660 (GRCm39)	S324P	probably benign	Het
Ptprk	A	T	10: 28,468,834 (GRCm39)	N1432I	possibly damaging	Het
R3hdm2	T	C	10: 127,328,515 (GRCm39)	S746P	probably benign	Het
Rnf220	G	A	4: 117,135,015 (GRCm39)	A412V	probably damaging	Het
Scel	G	A	14: 103,781,315 (GRCm39)	A154T	probably benign	Het
Sirpb1a	A	T	3: 15,475,664 (GRCm39)	N290K	probably damaging	Het
Sirpb1c	A	T	3: 15,886,310 (GRCm39)		probably null	Het
Sorbs2	A	T	8: 46,248,860 (GRCm39)	R704*	probably null	Het
Spast	T	C	17: 74,680,319 (GRCm39)	V427A	probably damaging	Het
Stxbp4	A	T	11: 90,482,937 (GRCm39)		probably null	Het
Thsd7a	C	A	6: 12,352,067 (GRCm39)	G1043C		Het
Tmem205	C	T	9: 21,832,410 (GRCm39)	C167Y	probably damaging	Het
Trappc9	A	T	15: 72,608,718 (GRCm39)	L897*	probably null	Het
Trim36	A	G	18: 46,302,495 (GRCm39)	F518L	probably benign	Het
Ttc12	T	G	9: 49,359,267 (GRCm39)	T402P	possibly damaging	Het
Vmn2r18	A	T	5: 151,485,682 (GRCm39)	L604*	probably null	Het
Wdr83	T	C	8: 85,806,460 (GRCm39)	N113D	possibly damaging	Het
Zfp628	G	A	7: 4,924,817 (GRCm39)	G1013E	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
R6595:Twnk	UTSW	19	44,998,931 (GRCm39)	missense	probably damaging	0.99
R6880:Twnk	UTSW	19	44,995,855 (GRCm39)	missense	probably benign
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'- AGCTTCAGTGAGACTCCCAG -3'
(R):5'- GGAGTATACAAACCCTTGAGCAAG -3'

Sequencing Primer
(F):5'- CCAGCCAGTCTTTTTAGACAGG -3'
(R):5'- TTGAGCAAGGCACTCCAC -3'

Posted On

2019-09-13