Mutagenetix > Incidental Mutation

Incidental Mutation 'R8826:Twnk'

673508

Institutional Source

Beutler Lab

Gene Symbol

Twnk

Ensembl Gene

ENSMUSG00000025209

Gene Name

twinkle mtDNA helicase

Synonyms

Peo1, D19Ertd626e, twinkle, Twinl

MMRRC Submission

068729-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8826 (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 44996434 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 289 (V289A)

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

Domain	Start	End	E-Value	Type
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: V289A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: V289A

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

Predicted Effect

probably benign
Transcript: ENSMUST00000130549

SMART Domains

Protein: ENSMUSP00000138321
Gene: ENSMUSG00000025207

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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: 99.6%
20x: 98.9%

Validation Efficiency

100% (91/91)

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: 90 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acta1	T	C	8: 124,619,978 (GRCm39)	M121V	probably damaging	Het
AI987944	A	T	7: 41,024,627 (GRCm39)	H120Q	possibly damaging	Het
Aldh9a1	C	G	1: 167,184,119 (GRCm39)	P205A	probably damaging	Het
Ank2	A	T	3: 126,740,951 (GRCm39)	N1644K	unknown	Het
Arfgef2	A	T	2: 166,677,386 (GRCm39)		probably benign	Het
Bpifb4	G	T	2: 153,783,817 (GRCm39)	V54L	probably benign	Het
Cacna1c	T	A	6: 118,711,836 (GRCm39)	M456L		Het
Cbln1	T	C	8: 88,198,420 (GRCm39)	N95S	probably benign	Het
Ccl11	G	T	11: 81,953,044 (GRCm39)	R67S	possibly damaging	Het
Cd200	G	A	16: 45,215,157 (GRCm39)	R165C	probably benign	Het
Cd2bp2	A	T	7: 126,793,257 (GRCm39)	M283K	probably damaging	Het
Cd86	G	T	16: 36,435,650 (GRCm39)	L256I	possibly damaging	Het
Ces2f	T	A	8: 105,679,734 (GRCm39)	F409Y	probably benign	Het
Cisd3	A	T	11: 97,579,158 (GRCm39)	Q100L	probably damaging	Het
Cntnap1	C	T	11: 101,077,655 (GRCm39)	R1106C	probably damaging	Het
Col6a2	A	T	10: 76,439,433 (GRCm39)	M777K	probably damaging	Het
Cp	A	G	3: 20,039,739 (GRCm39)	Y852C	probably damaging	Het
Ddx1	T	C	12: 13,277,332 (GRCm39)	E523G	probably damaging	Het
Ddx60	T	A	8: 62,398,990 (GRCm39)	D236E	probably benign	Het
Dnah9	A	T	11: 65,740,742 (GRCm39)	F4148Y	probably benign	Het
Dusp6	G	T	10: 99,099,469 (GRCm39)		probably benign	Het
Eif2a	C	A	3: 58,456,049 (GRCm39)	Y349*	probably null	Het
Enpep	G	A	3: 129,065,067 (GRCm39)	T874I	probably damaging	Het
Eps15	A	G	4: 109,169,505 (GRCm39)	D105G	possibly damaging	Het
Ess2	A	T	16: 17,722,954 (GRCm39)	M320K	probably damaging	Het
Exosc10	G	A	4: 148,653,159 (GRCm39)		probably null	Het
Fam13b	A	T	18: 34,631,070 (GRCm39)	N36K	probably damaging	Het
Fanca	T	C	8: 123,995,209 (GRCm39)	D1431G	probably benign	Het
Fgg	A	G	3: 82,921,625 (GRCm39)	D436G	probably benign	Het
Fip1l1	C	T	5: 74,725,188 (GRCm39)	T251I	probably benign	Het
Galnt2	A	G	8: 125,032,347 (GRCm39)	N104S	probably damaging	Het
Gmip	T	C	8: 70,268,748 (GRCm39)	S458P	possibly damaging	Het
Herc2	A	G	7: 55,756,144 (GRCm39)	D728G	probably benign	Het
Hif3a	A	G	7: 16,788,671 (GRCm39)	L100P	probably damaging	Het
Hmox2	C	G	16: 4,583,866 (GRCm39)	P282R	possibly damaging	Het
Hook1	A	T	4: 95,880,432 (GRCm39)	H90L	probably benign	Het
Igf2bp2	C	A	16: 21,883,866 (GRCm39)	G473C	probably damaging	Het
Ip6k2	T	C	9: 108,675,379 (GRCm39)		probably null	Het
Ipo5	G	T	14: 121,157,366 (GRCm39)	R68L	probably damaging	Het
Kif19b	A	G	5: 140,455,434 (GRCm39)	M347V	probably damaging	Het
Klhdc1	G	T	12: 69,305,392 (GRCm39)	W234L	probably damaging	Het
Krt8	A	G	15: 101,909,870 (GRCm39)	V178A	possibly damaging	Het
Lgi3	T	A	14: 70,768,712 (GRCm39)		probably null	Het
Litaf	T	G	16: 10,784,421 (GRCm39)	N30H	probably benign	Het
Lman2	C	A	13: 55,510,368 (GRCm39)	W12L	unknown	Het
Macf1	A	G	4: 123,276,022 (GRCm39)	L6182P	probably damaging	Het
Magi3	A	T	3: 103,992,662 (GRCm39)	M270K	probably benign	Het
Mapre2	A	T	18: 23,886,888 (GRCm39)		probably benign	Het
Minar1	T	A	9: 89,483,234 (GRCm39)	E721V	probably damaging	Het
Mllt10	T	A	2: 18,167,353 (GRCm39)	V426D	probably benign	Het
Mrgprf	A	G	7: 144,862,046 (GRCm39)	I203V	probably benign	Het
Mrnip	G	A	11: 50,067,688 (GRCm39)	C27Y	probably damaging	Het
Mrpl24	C	T	3: 87,829,701 (GRCm39)	R96*	probably null	Het
Nbas	T	A	12: 13,402,875 (GRCm39)		probably benign	Het
Nipal4	G	A	11: 46,045,470 (GRCm39)	T131M	possibly damaging	Het
Nlrp12	T	C	7: 3,289,621 (GRCm39)	D297G	possibly damaging	Het
Nol6	A	C	4: 41,121,823 (GRCm39)	M237R	probably benign	Het
Olig1	A	G	16: 91,067,027 (GRCm39)	E88G	probably benign	Het
Or1j19	T	A	2: 36,676,855 (GRCm39)	L106*	probably null	Het
Parg	A	G	14: 31,931,175 (GRCm39)	D265G	possibly damaging	Het
Pcdhgb8	A	T	18: 37,895,301 (GRCm39)	I124L	probably damaging	Het
Pign	A	G	1: 105,481,827 (GRCm39)	F822L	probably damaging	Het
Plch2	T	C	4: 155,071,140 (GRCm39)	T1080A	probably benign	Het
Pld4	A	T	12: 112,733,210 (GRCm39)	Y262F	possibly damaging	Het
Ppp1r12b	A	G	1: 134,693,730 (GRCm39)	V977A	probably benign	Het
Ppp6r3	C	T	19: 3,521,984 (GRCm39)	E565K		Het
Psmg2	A	G	18: 67,787,158 (GRCm39)		probably benign	Het
Ptcd3	C	T	6: 71,885,645 (GRCm39)	G27D	probably benign	Het
Retreg2	G	T	1: 75,119,525 (GRCm39)	G7C	unknown	Het
Rlbp1	A	T	7: 79,027,114 (GRCm39)	F182Y	probably benign	Het
Rnf148	G	C	6: 23,654,378 (GRCm39)	S206C	probably benign	Het
Sash1	A	G	10: 8,637,869 (GRCm39)	M1T	probably null	Het
Shank3	A	T	15: 89,433,598 (GRCm39)	T1448S	probably damaging	Het
Sipa1l1	A	G	12: 82,389,207 (GRCm39)	K478E	probably damaging	Het
Slitrk6	A	G	14: 110,988,801 (GRCm39)	I302T	probably benign	Het
Smc1b	A	G	15: 84,950,529 (GRCm39)	V1165A	probably damaging	Het
Sncaip	A	T	18: 53,048,381 (GRCm39)	H939L	probably benign	Het
Stn1	T	C	19: 47,524,709 (GRCm39)	D27G	probably damaging	Het
Sugct	T	G	13: 17,427,180 (GRCm39)		probably null	Het
Tmem259	A	G	10: 79,814,983 (GRCm39)	S214P	probably damaging	Het
Trdv4	G	A	14: 54,312,946 (GRCm39)	G107S	probably damaging	Het
Ttc3	C	T	16: 94,232,829 (GRCm39)	L957F	possibly damaging	Het
Ttn	A	G	2: 76,711,471 (GRCm39)	Y8357H	unknown	Het
Umodl1	A	G	17: 31,202,958 (GRCm39)	D437G	possibly damaging	Het
Upf1	T	C	8: 70,790,930 (GRCm39)	T590A	probably benign	Het
Vmn2r63	A	T	7: 42,576,441 (GRCm39)	D457E	probably benign	Het
Wdr82	A	T	9: 106,061,975 (GRCm39)	T213S	probably benign	Het
Zfp267	T	C	3: 36,218,255 (GRCm39)	Y93H	possibly damaging	Het
Zfp672	A	T	11: 58,220,590 (GRCm39)	M3K	unknown	Het
Zfyve26	A	G	12: 79,285,742 (GRCm39)	V2345A	probably benign	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
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
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'- TGAAGCTACTAGGGGCTGAG -3'
(R):5'- GGGAAGACTTAAGCCTTGGTTTAAG -3'

Sequencing Primer
(F):5'- TACTAGGGGCTGAGGGTCAGG -3'
(R):5'- TTTAAGGCCTCCAGGGGAC -3'

Posted On

2021-07-15