Mutagenetix > Incidental Mutation

Incidental Mutation 'R2004:Top3a'

223432

Institutional Source

Beutler Lab

Gene Symbol

Top3a

Ensembl Gene

ENSMUSG00000002814

Gene Name

topoisomerase (DNA) III alpha

Synonyms

Top IIIa

MMRRC Submission

040013-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2004 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

60630884-60668191 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 60633315 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Glutamine at position 927 (P927Q)

Ref Sequence

ENSEMBL: ENSMUSP00000099729 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000002891] [ENSMUST00000102668] [ENSMUST00000117743] [ENSMUST00000120417]

AlphaFold

O70157

Predicted Effect

probably damaging
Transcript: ENSMUST00000002891
AA Change: P927Q

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000002891
Gene: ENSMUSG00000002814
AA Change: P927Q

Domain	Start	End	E-Value	Type
TOPRIM	35	169	5.04e-24	SMART
TOP1Bc	172	269	4.99e-37	SMART
TOP1Ac	315	569	1.47e-107	SMART
Pfam:zf-C4_Topoisom	655	694	1.7e-15	PFAM
Pfam:zf-GRF	813	854	9.7e-23	PFAM
low complexity region	884	896	N/A	INTRINSIC
Pfam:zf-GRF	897	941	7.9e-24	PFAM
ZnF_C2HC	985	1001	7.06e-2	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000102668
AA Change: P927Q

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000099729
Gene: ENSMUSG00000002814
AA Change: P927Q

Domain	Start	End	E-Value	Type
TOPRIM	35	169	5.04e-24	SMART
TOP1Bc	172	269	4.99e-37	SMART
TOP1Ac	315	569	1.47e-107	SMART
Pfam:zf-C4_Topoisom	655	694	5.9e-16	PFAM
Pfam:zf-GRF	813	854	2.6e-21	PFAM
low complexity region	884	896	N/A	INTRINSIC
Pfam:zf-GRF	897	941	4.2e-22	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000117743

SMART Domains

Protein: ENSMUSP00000113057
Gene: ENSMUSG00000002814

Domain	Start	End	E-Value	Type
TOPRIM	10	144	5.04e-24	SMART
TOP1Bc	147	244	4.99e-37	SMART
TOP1Ac	290	544	1.47e-107	SMART
Pfam:zf-C4_Topoisom	630	669	4.6e-16	PFAM
ZnF_C2HC	755	771	7.06e-2	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000120417

SMART Domains

Protein: ENSMUSP00000113653
Gene: ENSMUSG00000002814

Domain	Start	End	E-Value	Type
TOPRIM	10	144	5.04e-24	SMART
TOP1Bc	147	244	4.99e-37	SMART
TOP1Ac	290	544	1.47e-107	SMART
Pfam:zf-C4_Topoisom	630	666	1.9e-13	PFAM

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 94.9%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
PHENOTYPE: Mice homozygous for a null allele die shortly after implantation and the induction of decidual reaction. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aass	A	T	6: 23,092,561 (GRCm39)	Y146*	probably null	Het
Adcy2	A	G	13: 68,944,722 (GRCm39)	L220P	probably damaging	Het
Agl	T	C	3: 116,574,914 (GRCm39)	Y660C	probably damaging	Het
Ak1	A	G	2: 32,519,622 (GRCm39)	T17A	probably benign	Het
Amph	G	A	13: 19,326,198 (GRCm39)	V643M	probably damaging	Het
Ankrd11	A	T	8: 123,629,161 (GRCm39)		probably null	Het
Ap5b1	T	C	19: 5,620,502 (GRCm39)	S641P	possibly damaging	Het
Apoc4	A	G	7: 19,415,304 (GRCm39)	M1T	probably null	Het
Arhgap5	T	C	12: 52,564,817 (GRCm39)	V596A	probably benign	Het
Ascc3	A	G	10: 50,493,838 (GRCm39)	E91G	probably damaging	Het
Bach2	T	A	4: 32,580,055 (GRCm39)	V637E	probably benign	Het
Bicd2	T	G	13: 49,532,881 (GRCm39)	L489R	possibly damaging	Het
Bltp1	C	T	3: 36,949,527 (GRCm39)	T2I	possibly damaging	Het
Boc	A	T	16: 44,322,007 (GRCm39)		probably null	Het
Cbln2	T	A	18: 86,734,791 (GRCm39)	V188D	probably damaging	Het
Ccl11	A	C	11: 81,953,123 (GRCm39)	T94P	probably damaging	Het
Cd109	A	T	9: 78,611,044 (GRCm39)	H1220L	probably benign	Het
Cd226	A	G	18: 89,265,435 (GRCm39)	I125V	probably benign	Het
Cep135	T	A	5: 76,780,176 (GRCm39)		probably null	Het
Cgnl1	T	G	9: 71,537,821 (GRCm39)	E1233A	probably damaging	Het
Ckap5	T	A	2: 91,437,891 (GRCm39)	D1597E	possibly damaging	Het
Clptm1	A	G	7: 19,380,762 (GRCm39)	I63T	possibly damaging	Het
Cpsf7	C	T	19: 10,518,073 (GRCm39)	P428S	probably damaging	Het
Cuedc1	C	T	11: 88,068,216 (GRCm39)	P155S	probably damaging	Het
Dgkb	T	C	12: 38,134,228 (GRCm39)	Y45H	probably damaging	Het
Dglucy	T	C	12: 100,823,181 (GRCm39)	F459L	probably damaging	Het
Dmp1	T	A	5: 104,359,790 (GRCm39)	D155E	possibly damaging	Het
Dnah1	T	A	14: 31,023,813 (GRCm39)	I960F	possibly damaging	Het
Drosha	G	T	15: 12,915,467 (GRCm39)	M795I	probably damaging	Het
Dsg1b	A	G	18: 20,529,532 (GRCm39)	T326A	probably damaging	Het
Dusp16	T	G	6: 134,695,802 (GRCm39)	N343T	probably benign	Het
Faim2	T	C	15: 99,398,127 (GRCm39)	S274G	possibly damaging	Het
Fhip2a	G	T	19: 57,370,324 (GRCm39)	V523L	probably benign	Het
Fndc1	T	C	17: 8,023,761 (GRCm39)	R65G	probably damaging	Het
Fnip2	A	T	3: 79,419,632 (GRCm39)		probably benign	Het
Grm3	T	C	5: 9,639,793 (GRCm39)	Y84C	possibly damaging	Het
Herc2	T	C	7: 55,787,607 (GRCm39)	F1755L	probably damaging	Het
Hivep1	C	T	13: 42,313,625 (GRCm39)	T1955I	possibly damaging	Het
Ift20	T	C	11: 78,431,797 (GRCm39)	I97T	probably damaging	Het
Il36rn	T	C	2: 24,171,376 (GRCm39)	C155R	probably damaging	Het
Lca5l	T	A	16: 95,963,849 (GRCm39)	K358N	probably damaging	Het
Lca5l	T	C	16: 95,977,218 (GRCm39)	N196S	possibly damaging	Het
Maf1	G	A	15: 76,237,563 (GRCm39)	D175N	probably damaging	Het
Mical3	T	C	6: 120,928,283 (GRCm39)	K996E	probably damaging	Het
Midn	A	G	10: 79,990,983 (GRCm39)	N331S	probably benign	Het
Mki67	T	A	7: 135,300,238 (GRCm39)	K1599*	probably null	Het
Mlx	A	G	11: 100,979,805 (GRCm39)	Q162R	possibly damaging	Het
Nalf1	A	G	8: 9,820,607 (GRCm39)	S138P	probably benign	Het
Ngp	T	C	9: 110,249,929 (GRCm39)	C76R	probably damaging	Het
Nin	C	T	12: 70,072,251 (GRCm39)	G1210D	probably benign	Het
Nlgn1	A	G	3: 25,488,034 (GRCm39)	I738T	probably benign	Het
Nop53	A	C	7: 15,672,153 (GRCm39)	F465C	probably damaging	Het
Npas3	A	G	12: 54,114,680 (GRCm39)	D503G	possibly damaging	Het
Npbwr1	T	A	1: 5,986,570 (GRCm39)	S315C	probably damaging	Het
Nup42	G	T	5: 24,386,989 (GRCm39)	G260*	probably null	Het
Ogdh	G	C	11: 6,284,626 (GRCm39)	R200P	possibly damaging	Het
Or4b13	T	A	2: 90,083,036 (GRCm39)	I99L	probably benign	Het
Or52n20	A	G	7: 104,320,808 (GRCm39)	T300A	possibly damaging	Het
Or5m13b	T	G	2: 85,753,939 (GRCm39)		probably null	Het
Or6ae1	C	T	7: 139,742,729 (GRCm39)	V45I	probably damaging	Het
Or7g16	G	A	9: 18,726,801 (GRCm39)	S263L	probably benign	Het
Or7g33	A	T	9: 19,448,688 (GRCm39)	C179*	probably null	Het
Ovgp1	T	A	3: 105,894,309 (GRCm39)		probably benign	Het
Papln	T	A	12: 83,819,992 (GRCm39)	C150S	probably damaging	Het
Pde1c	A	T	6: 56,135,996 (GRCm39)	L316Q	probably damaging	Het
Pdlim2	C	T	14: 70,402,228 (GRCm39)	R296H	probably damaging	Het
Piezo2	G	T	18: 63,277,997 (GRCm39)	D302E	probably damaging	Het
Pirb	A	T	7: 3,720,637 (GRCm39)	L287Q	probably benign	Het
Plin1	A	G	7: 79,375,378 (GRCm39)		probably benign	Het
Plxnc1	A	G	10: 94,688,484 (GRCm39)	I698T	probably damaging	Het
Ppp1r12c	G	T	7: 4,485,974 (GRCm39)	C572*	probably null	Het
Ptgis	T	C	2: 167,056,769 (GRCm39)	M273V	possibly damaging	Het
Samd14	C	A	11: 94,914,110 (GRCm39)	T283K	probably damaging	Het
Scnn1g	A	T	7: 121,337,411 (GRCm39)	K91*	probably null	Het
Slc24a4	A	G	12: 102,180,166 (GRCm39)	Q95R	probably damaging	Het
Slfn9	T	G	11: 82,879,027 (GRCm39)	D34A	probably benign	Het
Smarca4	A	T	9: 21,588,776 (GRCm39)	I1193F	probably damaging	Het
Spata31e5	A	G	1: 28,816,260 (GRCm39)	W591R	probably damaging	Het
Sphkap	T	C	1: 83,255,632 (GRCm39)	M706V	probably benign	Het
Stard9	C	A	2: 120,504,117 (GRCm39)	S221R	probably damaging	Het
Stxbp1	T	C	2: 32,688,201 (GRCm39)	D488G	probably damaging	Het
Sugp2	C	T	8: 70,695,306 (GRCm39)		probably null	Het
Tekt5	T	C	16: 10,213,070 (GRCm39)	I72V	probably benign	Het
Themis	T	A	10: 28,658,720 (GRCm39)	N582K	probably benign	Het
Tmed11	C	A	5: 108,934,000 (GRCm39)	M65I	possibly damaging	Het
Trpa1	A	T	1: 14,976,207 (GRCm39)	N165K	possibly damaging	Het
Tsfm	A	G	10: 126,866,663 (GRCm39)	S2P	probably damaging	Het
Wdr47	C	A	3: 108,534,758 (GRCm39)	S559*	probably null	Het
Wnt2b	T	C	3: 104,860,331 (GRCm39)	Y192C	probably damaging	Het
Zfp280b	A	G	10: 75,874,370 (GRCm39)	D83G	probably benign	Het
Zfp345	T	C	2: 150,314,038 (GRCm39)	T500A	possibly damaging	Het
Zfp78	T	A	7: 6,382,074 (GRCm39)	C343S	probably damaging	Het

Other mutations in Top3a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01712:Top3a	APN	11	60,652,562 (GRCm39)	missense	probably damaging	1.00
IGL02935:Top3a	APN	11	60,653,354 (GRCm39)	missense	possibly damaging	0.53
R0057:Top3a	UTSW	11	60,631,510 (GRCm39)	missense	probably benign
R0057:Top3a	UTSW	11	60,631,510 (GRCm39)	missense	probably benign
R0369:Top3a	UTSW	11	60,633,615 (GRCm39)	missense	probably damaging	1.00
R1171:Top3a	UTSW	11	60,641,419 (GRCm39)	missense	probably benign	0.02
R1459:Top3a	UTSW	11	60,650,188 (GRCm39)	missense	probably damaging	1.00
R1621:Top3a	UTSW	11	60,641,433 (GRCm39)	missense	probably damaging	1.00
R1812:Top3a	UTSW	11	60,650,188 (GRCm39)	missense	probably damaging	1.00
R1839:Top3a	UTSW	11	60,644,714 (GRCm39)	missense	probably damaging	1.00
R1873:Top3a	UTSW	11	60,638,810 (GRCm39)	nonsense	probably null
R2277:Top3a	UTSW	11	60,636,700 (GRCm39)	missense	possibly damaging	0.95
R2406:Top3a	UTSW	11	60,646,838 (GRCm39)	missense	probably damaging	1.00
R2418:Top3a	UTSW	11	60,638,842 (GRCm39)	missense	possibly damaging	0.95
R3196:Top3a	UTSW	11	60,650,182 (GRCm39)	missense	probably damaging	1.00
R3879:Top3a	UTSW	11	60,634,765 (GRCm39)	missense	possibly damaging	0.92
R4695:Top3a	UTSW	11	60,633,238 (GRCm39)	missense	probably benign	0.40
R4715:Top3a	UTSW	11	60,633,823 (GRCm39)	nonsense	probably null
R4768:Top3a	UTSW	11	60,653,316 (GRCm39)	missense	probably damaging	1.00
R4910:Top3a	UTSW	11	60,643,204 (GRCm39)	splice site	probably benign
R5305:Top3a	UTSW	11	60,653,365 (GRCm39)	missense	possibly damaging	0.56
R5387:Top3a	UTSW	11	60,653,316 (GRCm39)	missense	probably damaging	1.00
R5419:Top3a	UTSW	11	60,653,348 (GRCm39)	missense	probably damaging	1.00
R5806:Top3a	UTSW	11	60,667,746 (GRCm39)	critical splice donor site	probably null
R6162:Top3a	UTSW	11	60,636,763 (GRCm39)	missense	probably damaging	1.00
R6279:Top3a	UTSW	11	60,640,234 (GRCm39)	missense	probably benign	0.02
R6300:Top3a	UTSW	11	60,640,234 (GRCm39)	missense	probably benign	0.02
R6381:Top3a	UTSW	11	60,634,849 (GRCm39)	missense	probably damaging	1.00
R6383:Top3a	UTSW	11	60,640,285 (GRCm39)	missense	probably benign	0.30
R6767:Top3a	UTSW	11	60,641,579 (GRCm39)	missense	possibly damaging	0.84
R6919:Top3a	UTSW	11	60,640,319 (GRCm39)	missense	probably damaging	1.00
R7299:Top3a	UTSW	11	60,638,974 (GRCm39)	missense	probably damaging	0.99
R7301:Top3a	UTSW	11	60,638,974 (GRCm39)	missense	probably damaging	0.99
R7442:Top3a	UTSW	11	60,644,744 (GRCm39)	missense	possibly damaging	0.66
R7690:Top3a	UTSW	11	60,647,206 (GRCm39)	missense	probably damaging	1.00
R7786:Top3a	UTSW	11	60,667,792 (GRCm39)	missense	probably damaging	1.00
R7792:Top3a	UTSW	11	60,633,790 (GRCm39)	missense	probably benign
R8790:Top3a	UTSW	11	60,631,363 (GRCm39)	missense	possibly damaging	0.87
R8818:Top3a	UTSW	11	60,633,877 (GRCm39)	missense	probably damaging	1.00
R8867:Top3a	UTSW	11	60,633,481 (GRCm39)	missense	probably benign	0.00
R8914:Top3a	UTSW	11	60,631,405 (GRCm39)	missense	probably damaging	1.00
R9031:Top3a	UTSW	11	60,636,695 (GRCm39)	missense	probably damaging	0.99
R9102:Top3a	UTSW	11	60,647,155 (GRCm39)	missense	probably damaging	1.00
R9103:Top3a	UTSW	11	60,654,253 (GRCm39)	critical splice acceptor site	probably null
R9130:Top3a	UTSW	11	60,641,401 (GRCm39)	critical splice donor site	probably null
R9548:Top3a	UTSW	11	60,644,768 (GRCm39)	missense	probably benign	0.19
R9578:Top3a	UTSW	11	60,647,517 (GRCm39)	missense	probably damaging	0.99
R9732:Top3a	UTSW	11	60,640,391 (GRCm39)	missense	probably benign	0.01
R9774:Top3a	UTSW	11	60,638,998 (GRCm39)	missense	probably damaging	0.98
X0063:Top3a	UTSW	11	60,641,470 (GRCm39)	nonsense	probably null
X0065:Top3a	UTSW	11	60,654,224 (GRCm39)	missense	probably damaging	1.00
Z1176:Top3a	UTSW	11	60,633,463 (GRCm39)	missense	probably benign	0.32
Z1177:Top3a	UTSW	11	60,633,642 (GRCm39)	missense	possibly damaging	0.56
Z1186:Top3a	UTSW	11	60,641,410 (GRCm39)	missense	probably benign
Z1187:Top3a	UTSW	11	60,641,410 (GRCm39)	missense	probably benign
Z1188:Top3a	UTSW	11	60,641,410 (GRCm39)	missense	probably benign
Z1189:Top3a	UTSW	11	60,641,410 (GRCm39)	missense	probably benign
Z1190:Top3a	UTSW	11	60,641,410 (GRCm39)	missense	probably benign
Z1191:Top3a	UTSW	11	60,641,410 (GRCm39)	missense	probably benign
Z1192:Top3a	UTSW	11	60,641,410 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- AACGCAATGCCCTGCTGATC -3'
(R):5'- ACTTCTTCCTGTGGGCTGAC -3'

Sequencing Primer
(F):5'- GCTGATCCTCACTACACCGATATG -3'
(R):5'- TGACAGCAGCCATTCCACTGG -3'

Posted On

2014-08-25