Mutagenetix > Incidental Mutation

Incidental Mutation 'R7401:Twnk'

574211

Institutional Source

Beutler Lab

Gene Symbol

Twnk

Ensembl Gene

ENSMUSG00000025209

Gene Name

twinkle mtDNA helicase

Synonyms

twinkle, Twinl, Peo1, D19Ertd626e

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7401 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

45006558-45012762 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 45011780 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 645 (D645G)

Ref Sequence

ENSEMBL: ENSMUSP00000026227 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000026227] [ENSMUST00000039016] [ENSMUST00000179108]

AlphaFold

Q8CIW5

Predicted Effect

probably benign
Transcript: ENSMUST00000026227
AA Change: D645G

PolyPhen 2 Score 0.147 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000026227
Gene: ENSMUSG00000025209
AA Change: D645G

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: ENSMUST00000039016

SMART Domains

Protein: ENSMUSP00000045478
Gene: ENSMUSG00000035342

Domain	Start	End	E-Value	Type
low complexity region	99	105	N/A	INTRINSIC
low complexity region	187	199	N/A	INTRINSIC
low complexity region	242	265	N/A	INTRINSIC
low complexity region	267	321	N/A	INTRINSIC
low complexity region	375	407	N/A	INTRINSIC
low complexity region	412	423	N/A	INTRINSIC
Pfam:Fez1	441	639	4.2e-82	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000179108

SMART Domains

Protein: ENSMUSP00000137571
Gene: ENSMUSG00000035342

Domain	Start	End	E-Value	Type
low complexity region	99	105	N/A	INTRINSIC
low complexity region	187	199	N/A	INTRINSIC
low complexity region	242	265	N/A	INTRINSIC
low complexity region	267	321	N/A	INTRINSIC
low complexity region	375	407	N/A	INTRINSIC
low complexity region	412	423	N/A	INTRINSIC
Pfam:Fez1	441	639	4.2e-82	PFAM

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2610318N02Rik	A	T	16: 17,118,404	L152Q	probably benign	Het
Abcg3	A	T	5: 104,966,774	N292K	probably damaging	Het
Adamts3	T	A	5: 89,707,450		probably null	Het
Adgrg7	T	C	16: 56,742,418	N519D	probably benign	Het
Adsl	A	G	15: 80,962,782	H263R	probably damaging	Het
Ak9	A	T	10: 41,423,004	D1567V	unknown	Het
Bscl2	T	C	19: 8,846,550	F280L	possibly damaging	Het
Cacna1b	T	A	2: 24,679,294	T873S	probably benign	Het
Cacna1c	T	C	6: 119,052,708		probably null	Het
Cast	G	T	13: 74,808,458	A18E	unknown	Het
Ccdc114	A	C	7: 45,942,765	Q323P	probably damaging	Het
Cd207	A	C	6: 83,677,848		probably benign	Het
Cd79b	A	G	11: 106,312,852	S130P	probably benign	Het
Cfap52	A	T	11: 67,949,633	N157K	probably benign	Het
Cfap57	C	T	4: 118,614,931	V84I	probably benign	Het
Chaf1b	G	T	16: 93,884,380		probably benign	Het
Cntn1	A	G	15: 92,317,989	I968V	probably benign	Het
Cntn5	C	T	9: 9,833,461	V362I	probably benign	Het
Crem	A	G	18: 3,295,329	S80P	probably damaging	Het
Csnk1g3	C	T	18: 53,930,318	T267I	probably damaging	Het
Cyth1	A	T	11: 118,182,251	N274K	possibly damaging	Het
Dicer1	C	T	12: 104,712,278	G594S	probably benign	Het
Enpp1	C	T	10: 24,645,282	C849Y	probably damaging	Het
Fam193a	A	G	5: 34,465,635	E1189G	possibly damaging	Het
Fermt1	C	A	2: 132,917,559	V426L	probably benign	Het
Fes	A	G	7: 80,378,776		probably null	Het
Gm16486	T	C	8: 70,717,272	I1337T	probably benign	Het
Gmeb1	C	A	4: 132,225,774	L560F	probably damaging	Het
Hace1	T	C	10: 45,670,626	L452P	probably damaging	Het
Hecw2	T	A	1: 53,904,343	H975L	probably damaging	Het
Idh2	GGTCCCAG	GG	7: 80,098,329		probably benign	Het
Il1r2	T	A	1: 40,123,210	C338S	probably damaging	Het
Kcnb1	T	C	2: 167,188,284	S114G	probably damaging	Het
Lce1c	A	T	3: 92,680,316	T17S	unknown	Het
Lhfpl4	C	A	6: 113,176,666	L141F	possibly damaging	Het
Ms4a14	T	C	19: 11,302,230	E988G	possibly damaging	Het
Naip5	T	C	13: 100,219,696	Q1137R	probably benign	Het
Naip5	G	T	13: 100,219,697	Q1137K	not run	Het
Neurod1	T	A	2: 79,454,946	D31V	probably benign	Het
Neurod4	A	G	10: 130,271,058	C116R	probably damaging	Het
Nisch	A	G	14: 31,206,580	V28A	probably benign	Het
Olfr1174-ps	T	G	2: 88,311,428	M123L	probably benign	Het
Olfr1245	A	G	2: 89,575,105	V207A	probably benign	Het
Pabpc4l	A	T	3: 46,446,252	I319N	probably damaging	Het
Pabpc4l	T	A	3: 46,446,589	R207W	probably damaging	Het
Pcm1	G	A	8: 41,309,531	D1371N	probably damaging	Het
Peg10	G	GGTC	6: 4,756,452		probably benign	Het
Plxnc1	C	T	10: 94,871,005	A557T	probably benign	Het
Prkdc	T	A	16: 15,648,738	V58D	probably damaging	Het
Prpf40a	A	G	2: 53,156,947	V259A	probably benign	Het
Psmd3	A	T	11: 98,685,640	T123S	probably benign	Het
Ptgr2	G	T	12: 84,292,329		probably benign	Het
Ptprr	A	G	10: 116,048,236	H66R	probably benign	Het
Rftn2	A	G	1: 55,194,242		probably null	Het
Rsph14	T	A	10: 75,029,796	E70V	possibly damaging	Het
Slc24a5	G	A	2: 125,088,191	V471I	probably benign	Het
Sorbs1	G	C	19: 40,376,800	R180G	probably benign	Het
Spag9	A	T	11: 94,097,689	T862S	probably benign	Het
Ssbp2	T	A	13: 91,690,883	D291E	probably benign	Het
Supt5	T	C	7: 28,323,772	K329E	probably damaging	Het
Syne2	G	T	12: 75,967,381	K3115N	probably damaging	Het
Tars	A	T	15: 11,392,009	L239*	probably null	Het
Tbxa2r	T	C	10: 81,332,791	Y105H	probably benign	Het
Tesk1	T	A	4: 43,445,743	D265E	probably damaging	Het
Tril	T	C	6: 53,818,281	D652G	possibly damaging	Het
Tsga10	T	C	1: 37,834,187	R204G	probably null	Het
Umodl1	A	T	17: 30,998,148	D1118V	probably damaging	Het
Unc119	T	C	11: 78,347,245	I83T	probably benign	Het
Unc80	T	C	1: 66,646,415	W2233R	possibly damaging	Het
Vmn1r45	T	A	6: 89,933,434	T185S	possibly damaging	Het
Vmn2r111	G	T	17: 22,571,086	T313K	possibly damaging	Het
Wdr4	A	G	17: 31,509,832	L123S	probably damaging	Het
Zfpm2	A	G	15: 41,102,990	E957G	possibly damaging	Het

Other mutations in Twnk

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00858:Twnk	APN	19	45007626	missense	probably benign	0.03
IGL01367:Twnk	APN	19	45011651	missense	possibly damaging	0.92
IGL01736:Twnk	APN	19	45010188	missense	probably damaging	0.97
IGL02724:Twnk	APN	19	45008118	missense	probably damaging	0.99
IGL03368:Twnk	APN	19	45010492	missense	probably damaging	0.99
R0121:Twnk	UTSW	19	45009265	unclassified	probably benign
R0389:Twnk	UTSW	19	45008139	missense	possibly damaging	0.67
R0427:Twnk	UTSW	19	45007587	missense	probably benign	0.00
R0443:Twnk	UTSW	19	45008139	missense	possibly damaging	0.67
R0501:Twnk	UTSW	19	45007746	missense	probably damaging	1.00
R0791:Twnk	UTSW	19	45010254	unclassified	probably benign
R1193:Twnk	UTSW	19	45007790	missense	probably damaging	1.00
R1470:Twnk	UTSW	19	45009381	missense	probably damaging	1.00
R1470:Twnk	UTSW	19	45009381	missense	probably damaging	1.00
R1487:Twnk	UTSW	19	45008376	critical splice donor site	probably null
R1556:Twnk	UTSW	19	45009411	missense	possibly damaging	0.80
R3895:Twnk	UTSW	19	45007451	missense	probably damaging	0.98
R5652:Twnk	UTSW	19	45007293	missense	possibly damaging	0.85
R6373:Twnk	UTSW	19	45009381	missense	probably damaging	1.00
R6595:Twnk	UTSW	19	45010492	missense	probably damaging	0.99
R6880:Twnk	UTSW	19	45007416	missense	probably benign
R7349:Twnk	UTSW	19	45010161	missense	possibly damaging	0.65
R7417:Twnk	UTSW	19	45010564	splice site	probably null
R7798:Twnk	UTSW	19	45007668	missense	probably benign	0.00
R7994:Twnk	UTSW	19	45007838	missense	probably benign	0.03
R8698:Twnk	UTSW	19	45007860	missense	probably benign
R8826:Twnk	UTSW	19	45007995	missense	probably benign
R8855:Twnk	UTSW	19	45011833	nonsense	probably null
R8866:Twnk	UTSW	19	45011833	nonsense	probably null
R8972:Twnk	UTSW	19	45011710	missense	probably damaging	1.00
R9683:Twnk	UTSW	19	45010183	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TCTCCTTTAGGCAAGCCAAG -3'
(R):5'- TATATGGAAGAGCCCCAGCAG -3'

Sequencing Primer
(F):5'- GCAGACAATGTTCTGATCTTACAGG -3'
(R):5'- AGAAGGCCTGCTCCACCAG -3'

Posted On

2019-09-13