Mutagenetix > Incidental Mutation

Incidental Mutation 'R4774:Tdp1'

367787

Institutional Source

Beutler Lab

Gene Symbol

Tdp1

Ensembl Gene

ENSMUSG00000021177

Gene Name

tyrosyl-DNA phosphodiesterase 1

Synonyms

4921509N21Rik, SCAN1, 2810481F14Rik, E430034L06Rik, Gm40556

MMRRC Submission

042412-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.215) question?

Stock #

R4774 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

99850776-99921478 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 99868623 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Valine at position 259 (A259V)

Ref Sequence

ENSEMBL: ENSMUSP00000118656 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000021594
AA Change: A259V

PolyPhen 2 Score 0.565 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000021594
Gene: ENSMUSG00000021177
AA Change: A259V

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: ENSMUST00000151019

Predicted Effect

possibly damaging
Transcript: ENSMUST00000153627
AA Change: A259V

PolyPhen 2 Score 0.565 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000118656
Gene: ENSMUSG00000021177
AA Change: A259V

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

0.2432

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.7%
20x: 93.9%

Validation Efficiency

98% (97/99)

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: 85 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc9	T	C	6: 142,585,043 (GRCm39)	I844V	probably damaging	Het
Acnat1	T	A	4: 49,450,784 (GRCm39)	Y109F	probably benign	Het
Alox12b	T	C	11: 69,054,033 (GRCm39)	V205A	probably benign	Het
Arl6ip1	G	A	7: 117,721,208 (GRCm39)	R77C	probably damaging	Het
Atp8b1	A	G	18: 64,666,730 (GRCm39)	C1156R	possibly damaging	Het
Atp8b3	A	C	10: 80,372,156 (GRCm39)	N24K	probably damaging	Het
Bdh1	T	C	16: 31,273,954 (GRCm39)	V209A	possibly damaging	Het
Blm	A	T	7: 80,113,596 (GRCm39)	C1234S	probably damaging	Het
Caml	A	G	13: 55,779,740 (GRCm39)	D271G	possibly damaging	Het
Capn11	T	C	17: 45,944,006 (GRCm39)	D545G	probably benign	Het
Catspere1	T	C	1: 177,765,304 (GRCm39)		noncoding transcript	Het
Cep128	T	C	12: 91,200,969 (GRCm39)	E347G	probably damaging	Het
Cngb3	A	G	4: 19,415,713 (GRCm39)	T408A	possibly damaging	Het
Coa8	A	G	12: 111,679,823 (GRCm39)	T33A	possibly damaging	Het
Cog1	G	A	11: 113,548,253 (GRCm39)	R18Q	possibly damaging	Het
Cps1	T	C	1: 67,259,671 (GRCm39)	F1338L	probably damaging	Het
Csmd1	T	C	8: 16,059,369 (GRCm39)	H2122R	probably benign	Het
Ctu2	T	G	8: 123,207,851 (GRCm39)	S26A	probably benign	Het
Dbf4	G	A	5: 8,453,062 (GRCm39)		probably benign	Het
Ddx23	A	T	15: 98,545,116 (GRCm39)	D663E	probably benign	Het
Dpep2	T	C	8: 106,717,388 (GRCm39)	T123A	possibly damaging	Het
Eed	A	G	7: 89,613,976 (GRCm39)	I274T	probably damaging	Het
Eif3b	A	G	5: 140,405,255 (GRCm39)	D47G	probably benign	Het
Epas1	T	C	17: 87,113,186 (GRCm39)	V124A	probably damaging	Het
Fer1l6	T	C	15: 58,449,798 (GRCm39)	L668P	probably damaging	Het
Fnip2	C	A	3: 79,373,028 (GRCm39)	E1017*	probably null	Het
Gm43517	A	T	12: 49,436,690 (GRCm39)		probably benign	Het
Got1	A	G	19: 43,491,345 (GRCm39)		probably null	Het
H2-Eb2	T	A	17: 34,553,375 (GRCm39)	V187E	probably damaging	Het
H2-Q1	T	C	17: 35,540,242 (GRCm39)		probably benign	Het
Hpgd	T	C	8: 56,751,454 (GRCm39)	V94A	probably damaging	Het
Htra1	T	A	7: 130,586,756 (GRCm39)	N446K	probably benign	Het
Igkv3-4	T	A	6: 70,649,269 (GRCm39)	S89R	probably damaging	Het
Immt	C	T	6: 71,829,720 (GRCm39)	T142I	probably damaging	Het
Itpkb	C	A	1: 180,245,759 (GRCm39)	P759T	probably damaging	Het
Jmjd1c	G	A	10: 67,060,571 (GRCm39)	V688I	possibly damaging	Het
Kbtbd13	G	T	9: 65,298,025 (GRCm39)	R304S	probably benign	Het
Lama5	A	C	2: 179,827,734 (GRCm39)	L2176R	probably damaging	Het
Lrp1b	G	C	2: 40,551,544 (GRCm39)	L418V	probably null	Het
Lrrc4b	C	A	7: 44,111,796 (GRCm39)		probably null	Het
Lyst	A	G	13: 13,915,182 (GRCm39)	N3292S	probably damaging	Het
Mep1b	A	T	18: 21,219,241 (GRCm39)	I132F	probably benign	Het
Mettl2	A	G	11: 105,017,436 (GRCm39)		probably null	Het
Nherf2	T	C	17: 24,863,873 (GRCm39)	M1V	probably null	Het
Niban1	A	T	1: 151,591,445 (GRCm39)	D529V	probably damaging	Het
Nmd3	T	C	3: 69,652,569 (GRCm39)	L385S	probably benign	Het
Nol4	T	C	18: 23,045,683 (GRCm39)	E243G	probably damaging	Het
Odad1	T	A	7: 45,597,804 (GRCm39)	S571R	probably damaging	Het
Or4l1	T	A	14: 50,166,726 (GRCm39)	I92F	probably damaging	Het
Or51k1	A	G	7: 103,661,795 (GRCm39)	I38T	probably benign	Het
Or5j3	A	T	2: 86,129,042 (GRCm39)	N294I	possibly damaging	Het
Or8b52	A	G	9: 38,576,519 (GRCm39)	I207T	probably benign	Het
Pcnp	A	G	16: 55,837,522 (GRCm39)		probably benign	Het
Pla2g6	A	C	15: 79,171,818 (GRCm39)	C680G	probably damaging	Het
Plekha7	G	T	7: 115,744,178 (GRCm39)	D661E	probably damaging	Het
Prim1	A	T	10: 127,862,887 (GRCm39)		probably benign	Het
Psg29	T	A	7: 16,944,460 (GRCm39)	N323K	probably benign	Het
Ptrh2	G	A	11: 86,580,833 (GRCm39)	R150H	probably damaging	Het
Rasa1	A	G	13: 85,398,621 (GRCm39)		probably benign	Het
Rasa3	T	C	8: 13,627,501 (GRCm39)	D667G	probably benign	Het
Rnase2a	T	C	14: 51,493,201 (GRCm39)	N55D	probably damaging	Het
Rsf1	GCGGCGGCGGCGGCGGCGGC	GCGGCGGCGGCGGCGGCGGCGGCGGCGGC	7: 97,229,123 (GRCm39)		probably benign	Het
Sbp	T	A	17: 24,164,218 (GRCm39)	N133K	probably damaging	Het
Scml4	A	G	10: 42,833,743 (GRCm39)		probably benign	Het
Sema5b	T	A	16: 35,483,552 (GRCm39)	N1063K	probably damaging	Het
Serpind1	C	T	16: 17,154,272 (GRCm39)	T33M	probably benign	Het
Shroom3	G	T	5: 93,090,945 (GRCm39)	V1151F	probably damaging	Het
Slc15a2	A	T	16: 36,602,057 (GRCm39)	L80*	probably null	Het
Sorcs3	A	G	19: 48,782,602 (GRCm39)	D1039G	probably benign	Het
Spon1	A	G	7: 113,639,102 (GRCm39)	E776G	probably damaging	Het
Tex46	C	A	4: 136,337,991 (GRCm39)	P61Q	probably benign	Het
Tnr	T	A	1: 159,724,636 (GRCm39)	L1109Q	probably damaging	Het
Tns2	C	T	15: 102,017,369 (GRCm39)	R281C	probably damaging	Het
Tpra1	G	A	6: 88,887,661 (GRCm39)		probably benign	Het
Trim43c	A	T	9: 88,729,705 (GRCm39)	H383L	possibly damaging	Het
Trip6	A	G	5: 137,308,433 (GRCm39)	C439R	probably damaging	Het
Tsen2	C	T	6: 115,552,894 (GRCm39)	S398L	possibly damaging	Het
Tubgcp2	T	C	7: 139,576,074 (GRCm39)	D863G	probably damaging	Het
Ube2d2a	A	G	18: 35,903,498 (GRCm39)		probably benign	Het
Umad1	T	A	6: 8,427,181 (GRCm39)	F145I	probably damaging	Het
Unc5c	A	T	3: 141,534,278 (GRCm39)	E933V	probably damaging	Het
Vmn1r208	A	G	13: 22,956,646 (GRCm39)	F284L	probably benign	Het
Vmn2r53	T	A	7: 12,334,692 (GRCm39)	R323*	probably null	Het
Zan	G	A	5: 137,387,281 (GRCm39)	T4924I	unknown	Het
Zfp597	G	T	16: 3,683,851 (GRCm39)	Q302K	probably benign	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
R4859:Tdp1	UTSW	12	99,876,070 (GRCm39)	missense	probably benign	0.20
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'- CTGTTTGTCCAATAGAGGGCAG -3'
(R):5'- GCAGAGTTGTCTATGACCACAG -3'

Sequencing Primer
(F):5'- TTTGTCCAATAGAGGGCAGTCAAAC -3'
(R):5'- GAGTTGTCTATGACCACAGAACTAC -3'

Posted On

2015-12-29