Mutagenetix > Incidental Mutation

Incidental Mutation 'R4859:Tdp1'

372349

Institutional Source

Beutler Lab

Gene Symbol

Tdp1

Ensembl Gene

ENSMUSG00000021177

Gene Name

tyrosyl-DNA phosphodiesterase 1

Synonyms

4921509N21Rik, SCAN1, 2810481F14Rik, E430034L06Rik, Gm40556

MMRRC Submission

042470-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.220) question?

Stock #

R4859 (G1)

Quality Score

180

Status

Validated

Chromosome

Chromosomal Location

99850776-99921478 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 99876070 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Methionine at position 340 (I340M)

Ref Sequence

ENSEMBL: ENSMUSP00000118656 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021594] [ENSMUST00000153627]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000021594
AA Change: I340M

PolyPhen 2 Score 0.202 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000021594
Gene: ENSMUSG00000021177
AA Change: I340M

Domain	Start	End	E-Value	Type
low complexity region	13	32	N/A	INTRINSIC
Pfam:Tyr-DNA_phospho	164	583	2.7e-142	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000126424

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000128739

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151019

Predicted Effect

probably benign
Transcript: ENSMUST00000153627
AA Change: I340M

PolyPhen 2 Score 0.202 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000118656
Gene: ENSMUSG00000021177
AA Change: I340M

Domain	Start	End	E-Value	Type
low complexity region	13	32	N/A	INTRINSIC
Pfam:Tyr-DNA_phospho	166	583	2.4e-142	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000221445

Meta Mutation Damage Score

0.1217

Coding Region Coverage

1x: 98.9%
3x: 98.1%
10x: 95.5%
20x: 89.5%

Validation Efficiency

100% (112/112)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). [provided by RefSeq, Aug 2016]
PHENOTYPE: Mice homozygous for a null allele exhibit defective single strand DNA repair in neurons, decreased cerebellum size and increased sensitivity to topotecan. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam25	T	A	8: 41,207,580 (GRCm39)	V282E	probably benign	Het
Adam26b	T	C	8: 43,973,296 (GRCm39)	T569A	possibly damaging	Het
Adam6a	A	G	12: 113,509,609 (GRCm39)	N661D	probably damaging	Het
Adck1	G	A	12: 88,407,865 (GRCm39)	A199T	probably benign	Het
Adhfe1	A	G	1: 9,628,438 (GRCm39)	Y270C	probably damaging	Het
Aldh16a1	C	T	7: 44,796,731 (GRCm39)	R256H	probably benign	Het
Ap5z1	T	C	5: 142,459,748 (GRCm39)	M466T	possibly damaging	Het
Aspm	C	T	1: 139,397,131 (GRCm39)	L908F	probably damaging	Het
Atp8b2	T	A	3: 89,853,287 (GRCm39)	T743S	probably benign	Het
Bag2	G	T	1: 33,786,022 (GRCm39)	T100K	probably damaging	Het
Camk2a	A	G	18: 61,076,246 (GRCm39)		probably benign	Het
Ccdc158	A	G	5: 92,781,262 (GRCm39)	Y848H	probably damaging	Het
Ccp110	T	G	7: 118,324,653 (GRCm39)	V725G	possibly damaging	Het
Cdh6	A	G	15: 13,051,418 (GRCm39)	V405A	probably benign	Het
Ces2g	T	C	8: 105,694,094 (GRCm39)		probably null	Het
Cfap157	A	G	2: 32,667,554 (GRCm39)	F510L	probably benign	Het
Chd3	A	T	11: 69,250,722 (GRCm39)	M669K	possibly damaging	Het
Cnot10	C	T	9: 114,456,532 (GRCm39)	A168T	probably damaging	Het
Crybg1	A	G	10: 43,868,565 (GRCm39)	V1371A	probably damaging	Het
Dars2	A	G	1: 160,872,560 (GRCm39)	L547P	probably damaging	Het
Dis3	A	G	14: 99,325,226 (GRCm39)	C483R	probably damaging	Het
Dnah7b	T	A	1: 46,395,762 (GRCm39)	L3888Q	probably damaging	Het
Dpysl2	A	T	14: 67,066,888 (GRCm39)	Y182N	probably damaging	Het
Eif4g1	T	A	16: 20,500,923 (GRCm39)	F509L	probably benign	Het
Evc	T	C	5: 37,458,253 (GRCm39)	T85A	probably damaging	Het
Farsb	T	C	1: 78,444,609 (GRCm39)	T283A	probably benign	Het
Fem1al	G	T	11: 29,775,178 (GRCm39)	A93E	probably damaging	Het
Fgf14	C	A	14: 124,429,845 (GRCm39)	R30L	possibly damaging	Het
Gbe1	T	C	16: 70,275,289 (GRCm39)	L363P	probably damaging	Het
Gcg	A	G	2: 62,307,189 (GRCm39)	V124A	probably damaging	Het
Glb1l	A	G	1: 75,176,963 (GRCm39)		probably benign	Het
Gm5431	T	C	11: 48,780,409 (GRCm39)	E449G	probably damaging	Het
Gon4l	T	C	3: 88,802,655 (GRCm39)	S1089P	probably benign	Het
Hgd	T	C	16: 37,409,111 (GRCm39)	L25P	probably damaging	Het
Hnf1a	T	C	5: 115,093,311 (GRCm39)	H318R	possibly damaging	Het
Hsd17b7	A	C	1: 169,794,826 (GRCm39)	V71G	possibly damaging	Het
Hydin	T	C	8: 111,233,126 (GRCm39)	S1742P	possibly damaging	Het
Insyn2b	A	G	11: 34,353,154 (GRCm39)	S399G	probably benign	Het
Kank2	T	C	9: 21,691,078 (GRCm39)	E552G	probably benign	Het
Kcnq4	C	A	4: 120,573,810 (GRCm39)	R217L	probably damaging	Het
Klrg2	T	C	6: 38,604,540 (GRCm39)	*201W	probably null	Het
Kndc1	T	C	7: 139,501,821 (GRCm39)	S953P	probably benign	Het
Lama2	TTTGCGCATT	TTT	10: 26,919,639 (GRCm39)		probably null	Het
Lonp1	A	G	17: 56,933,587 (GRCm39)	V96A	probably benign	Het
Mgat4e	T	C	1: 134,469,478 (GRCm39)	K189E	possibly damaging	Het
Msantd5f8	A	G	4: 73,805,457 (GRCm39)	S351P	probably damaging	Het
Msh2	G	A	17: 88,026,187 (GRCm39)	V722I	possibly damaging	Het
Mtcl3	A	C	10: 29,026,390 (GRCm39)	M491L	probably benign	Het
N4bp2	T	C	5: 65,982,641 (GRCm39)	Y1632H	probably damaging	Het
Nlrc4	T	G	17: 74,743,032 (GRCm39)	K862T	probably damaging	Het
Notch4	A	T	17: 34,806,154 (GRCm39)	Q1750L	probably damaging	Het
Obscn	C	T	11: 58,972,849 (GRCm39)	V2066I	possibly damaging	Het
Or2v2	T	C	11: 49,003,993 (GRCm39)	K187E	probably damaging	Het
Or4c15	T	A	2: 88,760,627 (GRCm39)	I11L	probably benign	Het
Or4f14b	A	T	2: 111,775,156 (GRCm39)	I215N	probably damaging	Het
Or52d13	A	T	7: 103,110,243 (GRCm39)	Y57*	probably null	Het
Or5m8	T	C	2: 85,823,075 (GRCm39)	S305P	probably damaging	Het
Pde7a	T	A	3: 19,295,655 (GRCm39)		probably benign	Het
Pign	A	T	1: 105,575,892 (GRCm39)	Y249*	probably null	Het
Ppp1r17	A	T	6: 56,003,449 (GRCm39)	E87D	probably damaging	Het
Prss3	T	A	6: 41,350,857 (GRCm39)	Q211L	probably damaging	Het
Rapgef6	A	G	11: 54,526,989 (GRCm39)	E413G	probably benign	Het
Rnf150	A	G	8: 83,590,712 (GRCm39)	H25R	probably damaging	Het
Scamp2	T	C	9: 57,488,934 (GRCm39)		probably null	Het
Scap	T	A	9: 110,203,410 (GRCm39)		probably benign	Het
Sdc2	A	C	15: 33,032,602 (GRCm39)	K175N	probably damaging	Het
Serpinb6d	T	A	13: 33,851,547 (GRCm39)		probably null	Het
Sh3tc2	A	G	18: 62,146,164 (GRCm39)	N1181S	probably benign	Het
Slc44a2	T	C	9: 21,259,441 (GRCm39)	I46T	probably damaging	Het
Slfn8	A	G	11: 82,908,540 (GRCm39)	M1T	probably null	Het
Slitrk6	T	C	14: 110,989,315 (GRCm39)	T131A	probably damaging	Het
Spata1	C	G	3: 146,175,529 (GRCm39)	D326H	probably damaging	Het
Tbck	T	G	3: 132,507,288 (GRCm39)	S753R	probably benign	Het
Tmprss6	T	A	15: 78,330,877 (GRCm39)	Y50F	probably damaging	Het
Trank1	T	A	9: 111,194,078 (GRCm39)	S701T	probably benign	Het
Trbv17	A	T	6: 41,140,223 (GRCm39)	N26I	probably benign	Het
Trip12	A	T	1: 84,771,531 (GRCm39)	S248T	probably damaging	Het
Vmn2r53	T	G	7: 12,335,330 (GRCm39)	Q110P	probably damaging	Het
Vmn2r75	A	G	7: 85,797,611 (GRCm39)	V734A	probably benign	Het
Wfdc11	A	T	2: 164,507,415 (GRCm39)	M14K	probably null	Het
Xcr1	T	A	9: 123,685,712 (GRCm39)	M17L	probably benign	Het
Zbtb40	A	G	4: 136,716,070 (GRCm39)	I965T	probably damaging	Het
Zfp760	A	T	17: 21,942,511 (GRCm39)	H562L	probably damaging	Het
Zfp760	A	T	17: 21,942,516 (GRCm39)	R564*	probably null	Het
Znf41-ps	T	A	4: 145,555,283 (GRCm39)		noncoding transcript	Het
Zyg11a	A	T	4: 108,067,387 (GRCm39)	I41N	probably damaging	Het

Other mutations in Tdp1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00780:Tdp1	APN	12	99,859,907 (GRCm39)	missense	possibly damaging	0.79
IGL01099:Tdp1	APN	12	99,881,704 (GRCm39)	splice site	probably benign
IGL01295:Tdp1	APN	12	99,857,929 (GRCm39)	missense	probably benign	0.00
IGL01409:Tdp1	APN	12	99,875,940 (GRCm39)	missense	possibly damaging	0.83
IGL01482:Tdp1	APN	12	99,857,639 (GRCm39)	missense	probably benign
IGL03116:Tdp1	APN	12	99,921,290 (GRCm39)	missense	probably benign	0.27
BB004:Tdp1	UTSW	12	99,878,555 (GRCm39)	missense	probably damaging	1.00
BB014:Tdp1	UTSW	12	99,878,555 (GRCm39)	missense	probably damaging	1.00
R0008:Tdp1	UTSW	12	99,921,217 (GRCm39)	splice site	probably benign
R0033:Tdp1	UTSW	12	99,901,311 (GRCm39)	missense	probably benign	0.30
R0092:Tdp1	UTSW	12	99,921,248 (GRCm39)	missense	probably damaging	1.00
R0485:Tdp1	UTSW	12	99,876,101 (GRCm39)	missense	probably benign	0.30
R0611:Tdp1	UTSW	12	99,875,970 (GRCm39)	missense	probably benign
R0853:Tdp1	UTSW	12	99,901,326 (GRCm39)	missense	probably damaging	0.96
R1539:Tdp1	UTSW	12	99,878,571 (GRCm39)	missense	probably damaging	1.00
R1692:Tdp1	UTSW	12	99,921,260 (GRCm39)	missense	probably damaging	1.00
R1751:Tdp1	UTSW	12	99,857,602 (GRCm39)	splice site	probably null
R1767:Tdp1	UTSW	12	99,857,602 (GRCm39)	splice site	probably null
R3788:Tdp1	UTSW	12	99,858,011 (GRCm39)	splice site	probably benign
R3790:Tdp1	UTSW	12	99,858,011 (GRCm39)	splice site	probably benign
R3837:Tdp1	UTSW	12	99,860,967 (GRCm39)	critical splice acceptor site	probably null
R3917:Tdp1	UTSW	12	99,860,976 (GRCm39)	missense	probably damaging	1.00
R4209:Tdp1	UTSW	12	99,864,588 (GRCm39)	missense	probably damaging	1.00
R4211:Tdp1	UTSW	12	99,864,588 (GRCm39)	missense	probably damaging	1.00
R4509:Tdp1	UTSW	12	99,921,324 (GRCm39)	utr 3 prime	probably benign
R4774:Tdp1	UTSW	12	99,868,623 (GRCm39)	missense	possibly damaging	0.56
R5229:Tdp1	UTSW	12	99,859,919 (GRCm39)	missense	probably damaging	1.00
R5348:Tdp1	UTSW	12	99,881,765 (GRCm39)	missense	probably damaging	1.00
R5441:Tdp1	UTSW	12	99,876,544 (GRCm39)	missense	probably damaging	1.00
R5457:Tdp1	UTSW	12	99,861,005 (GRCm39)	nonsense	probably null
R5685:Tdp1	UTSW	12	99,868,611 (GRCm39)	missense	possibly damaging	0.51
R6329:Tdp1	UTSW	12	99,880,331 (GRCm39)	missense	probably benign	0.02
R6329:Tdp1	UTSW	12	99,880,330 (GRCm39)	missense	probably damaging	0.99
R7060:Tdp1	UTSW	12	99,877,947 (GRCm39)	missense	probably benign	0.02
R7066:Tdp1	UTSW	12	99,860,991 (GRCm39)	missense	probably benign
R7479:Tdp1	UTSW	12	99,857,654 (GRCm39)	missense	probably benign	0.00
R7927:Tdp1	UTSW	12	99,878,555 (GRCm39)	missense	probably damaging	1.00
R8556:Tdp1	UTSW	12	99,857,527 (GRCm39)	missense	probably benign	0.07
R8774:Tdp1	UTSW	12	99,877,917 (GRCm39)	missense	probably damaging	1.00
R8774-TAIL:Tdp1	UTSW	12	99,877,917 (GRCm39)	missense	probably damaging	1.00
R9521:Tdp1	UTSW	12	99,877,906 (GRCm39)	missense	probably damaging	0.98
Z1177:Tdp1	UTSW	12	99,877,892 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- GCAGAGGCGTTGTTGCAATG -3'
(R):5'- CTTGACGCCTATGAACCATGAG -3'

Sequencing Primer
(F):5'- TGTTGCAATGAAAGCCCCTG -3'
(R):5'- CCTATGAACCATGAGACACAGTGTG -3'

Posted On

2016-03-01