Mutagenetix > Incidental Mutation

Incidental Mutation 'R0427:Twnk'

38794

Institutional Source

Beutler Lab

Gene Symbol

Twnk

Ensembl Gene

ENSMUSG00000025209

Gene Name

twinkle mtDNA helicase

Synonyms

Peo1, D19Ertd626e, twinkle, Twinl

MMRRC Submission

038629-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0427 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

44994102-45001201 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 44996026 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 153 (E153G)

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: E153G

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)

SMART Domains

Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: E153G

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: 99.1%
3x: 98.3%
10x: 96.2%
20x: 92.9%

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam34	T	G	8: 44,105,493 (GRCm39)	T51P	probably benign	Het
Alpk1	A	T	3: 127,464,720 (GRCm39)	V1186E	probably damaging	Het
Ankfn1	T	C	11: 89,296,423 (GRCm39)	D102G	probably damaging	Het
Armc2	A	G	10: 41,876,406 (GRCm39)	I127T	possibly damaging	Het
Atp6v1b2	T	C	8: 69,554,084 (GRCm39)	L87P	probably damaging	Het
Atp9a	T	A	2: 168,482,617 (GRCm39)		probably null	Het
BC048679	C	G	7: 81,144,993 (GRCm39)	V123L	probably benign	Het
Birc7	G	A	2: 180,571,307 (GRCm39)		probably null	Het
Btbd9	C	T	17: 30,493,916 (GRCm39)	D492N	possibly damaging	Het
Cacna1d	T	A	14: 30,068,774 (GRCm39)	N155I	probably damaging	Het
Cd300lg	T	C	11: 101,933,852 (GRCm39)	V33A	probably damaging	Het
Cep290	A	G	10: 100,352,041 (GRCm39)	D742G	probably benign	Het
Cep95	A	G	11: 106,681,578 (GRCm39)	N14S	probably benign	Het
Cfap74	A	T	4: 155,525,734 (GRCm39)	M728L	probably benign	Het
Ctsll3	T	A	13: 60,949,205 (GRCm39)	T9S	probably benign	Het
Cyp3a44	A	G	5: 145,716,412 (GRCm39)	S393P	possibly damaging	Het
Dmbt1	T	A	7: 130,642,632 (GRCm39)	L150*	probably null	Het
Dnah2	A	G	11: 69,343,705 (GRCm39)	I2868T	probably damaging	Het
Dop1a	A	G	9: 86,389,585 (GRCm39)	H505R	probably damaging	Het
Exo1	A	G	1: 175,733,519 (GRCm39)	K781R	probably damaging	Het
Fam184a	A	G	10: 53,566,211 (GRCm39)	Y459H	probably damaging	Het
Foxp1	C	T	6: 98,907,164 (GRCm39)	D540N	probably damaging	Het
Fstl5	T	A	3: 76,615,034 (GRCm39)	Y698*	probably null	Het
Gm5141	T	C	13: 62,922,525 (GRCm39)	K215E	probably damaging	Het
Grik5	C	A	7: 24,757,923 (GRCm39)	R386L	probably benign	Het
Ikbke	A	T	1: 131,185,647 (GRCm39)	S620R	possibly damaging	Het
Kcnh3	A	T	15: 99,131,180 (GRCm39)	M518L	probably benign	Het
Lrrcc1	G	T	3: 14,623,416 (GRCm39)	A748S	probably damaging	Het
Mbd5	T	G	2: 49,169,091 (GRCm39)	S1191A	probably benign	Het
Med27	T	C	2: 29,390,283 (GRCm39)	I70T	probably damaging	Het
Mplkipl1	A	G	19: 61,163,908 (GRCm39)	Y176H	probably damaging	Het
Myh4	A	G	11: 67,149,479 (GRCm39)	D1737G	probably damaging	Het
Myo5a	A	G	9: 75,081,478 (GRCm39)	D1021G	probably benign	Het
Ncor1	T	C	11: 62,301,746 (GRCm39)	E212G	probably damaging	Het
Neb	A	T	2: 52,133,896 (GRCm39)	N3362K	possibly damaging	Het
Neb	A	G	2: 52,134,081 (GRCm39)	S3301P	probably damaging	Het
Neurod1	T	G	2: 79,284,526 (GRCm39)	K286Q	probably damaging	Het
Noc3l	T	C	19: 38,778,095 (GRCm39)	Q773R	probably benign	Het
Nup205	T	A	6: 35,171,398 (GRCm39)	N420K	probably benign	Het
Olfml3	A	T	3: 103,644,330 (GRCm39)	V113E	probably benign	Het
Opa1	T	C	16: 29,430,279 (GRCm39)	V439A	probably damaging	Het
Or13c7	A	G	4: 43,854,417 (GRCm39)	Y36C	probably damaging	Het
Or14j7	A	T	17: 38,234,520 (GRCm39)	H21L	probably benign	Het
Or1j14	C	T	2: 36,417,994 (GRCm39)	S190L	probably damaging	Het
Or1o11	T	A	17: 37,756,593 (GRCm39)	D60E	probably damaging	Het
Pcdhb11	T	C	18: 37,555,818 (GRCm39)	S383P	probably damaging	Het
Pkd1	T	C	17: 24,812,476 (GRCm39)	V3803A	probably damaging	Het
Plekhg1	A	G	10: 3,914,235 (GRCm39)	D1319G	probably benign	Het
Polq	T	A	16: 36,882,355 (GRCm39)	C1227*	probably null	Het
Pramel22	A	T	4: 143,380,993 (GRCm39)	N343K	probably benign	Het
Psmc1	T	C	12: 100,085,487 (GRCm39)	F283L	probably damaging	Het
Psmd8	T	C	7: 28,875,552 (GRCm39)	N189S	probably damaging	Het
Ptger4	G	A	15: 5,272,382 (GRCm39)	T104I	probably benign	Het
Ptpro	T	G	6: 137,345,294 (GRCm39)	V100G	possibly damaging	Het
Rab11fip1	T	A	8: 27,644,520 (GRCm39)	T422S	probably damaging	Het
Rad54l2	A	G	9: 106,570,891 (GRCm39)	L1143P	possibly damaging	Het
Rnf148	A	G	6: 23,654,072 (GRCm39)	M308T	probably damaging	Het
Sbsn	T	A	7: 30,451,523 (GRCm39)		probably benign	Het
Scube2	T	A	7: 109,424,044 (GRCm39)	T487S	probably benign	Het
Sema4c	C	A	1: 36,592,892 (GRCm39)	E109*	probably null	Het
Sipa1l2	A	T	8: 126,207,071 (GRCm39)	L544Q	probably damaging	Het
Slc28a2	A	G	2: 122,288,702 (GRCm39)	T603A	probably benign	Het
Tbc1d7	T	A	13: 43,306,563 (GRCm39)	T138S	probably benign	Het
Timd4	A	T	11: 46,710,084 (GRCm39)	T239S	probably benign	Het
Trp53bp1	A	G	2: 121,066,498 (GRCm39)	S743P	probably damaging	Het
Tspan10	T	A	11: 120,335,120 (GRCm39)	Y77N	probably damaging	Het
Ttc14	T	C	3: 33,857,633 (GRCm39)	S245P	probably damaging	Het
Ttf1	T	A	2: 28,955,054 (GRCm39)	S139R	probably benign	Het
Tubd1	C	A	11: 86,448,616 (GRCm39)	Q279K	possibly damaging	Het
Ush2a	A	G	1: 188,132,478 (GRCm39)	D900G	probably damaging	Het
Usp54	A	G	14: 20,620,432 (GRCm39)	V691A	probably benign	Het
Usp8	T	C	2: 126,559,952 (GRCm39)		probably benign	Het
Vmn1r231	C	T	17: 21,110,490 (GRCm39)	V142I	probably benign	Het
Vmn2r15	C	T	5: 109,434,953 (GRCm39)	A584T	probably damaging	Het
Vmn2r6	A	G	3: 64,467,008 (GRCm39)	S164P	probably damaging	Het
Vps16	A	G	2: 130,280,770 (GRCm39)	Y233C	probably benign	Het
Vwf	C	G	6: 125,650,902 (GRCm39)	H2511D	probably benign	Het
Wipf3	T	G	6: 54,460,882 (GRCm39)	L110R	possibly damaging	Het
Zfp945	T	A	17: 23,084,226 (GRCm39)	N11I	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
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
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'- AAAGGACGCTCCCACTTCCTTCTG -3'
(R):5'- TCCAGTTCACGACTTGTCACAACC -3'

Sequencing Primer
(F):5'- CTGCCTCTTCATTGACAAGAC -3'
(R):5'- TAGTAGCTTCAGGCCACGTAATC -3'

Posted On

2013-05-23