Mutagenetix > Incidental Mutations

Incidental Mutation 'R0558:Top2a'

45744

Institutional Source

Beutler Lab

Gene Symbol

Top2a

Ensembl Gene

ENSMUSG00000020914

Gene Name

topoisomerase (DNA) II alpha

Synonyms

Top-2, DNA Topoisomerase II alpha

MMRRC Submission

038750-MU

Accession Numbers

Ncbi RefSeq: NM_011623.2; MGI:98790

Is this an essential gene?

Probably essential (E-score: 0.969) question?

Stock #

R0558 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

98992943-99024189 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 98996839 bp

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 1281 (V1281A)

Ref Sequence

ENSEMBL: ENSMUSP00000068896 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000068031]

Predicted Effect

probably benign
Transcript: ENSMUST00000068031
AA Change: V1281A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000068896
Gene: ENSMUSG00000020914
AA Change: V1281A

Domain	Start	End	E-Value	Type
low complexity region	10	21	N/A	INTRINSIC
Blast:TOP2c	22	60	3e-12	BLAST
HATPase_c	75	224	1.81e-2	SMART
TOP2c	79	669	N/A	SMART
TOP4c	692	1166	3.58e-234	SMART
low complexity region	1192	1202	N/A	INTRINSIC
low complexity region	1226	1238	N/A	INTRINSIC
low complexity region	1261	1273	N/A	INTRINSIC
low complexity region	1291	1306	N/A	INTRINSIC
low complexity region	1407	1418	N/A	INTRINSIC
Pfam:DTHCT	1425	1518	1.1e-18	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000104097

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139460

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151997

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154332

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 93.8%

Validation Efficiency

100% (80/80)

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 nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia. [provided by RefSeq, Jul 2010]

Allele List at MGI

All alleles(47) : Targeted(1) Gene trapped(46)

Other mutations in this stock

Total: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A930017K11Rik	T	C	17: 25,947,549	N338S	probably benign	Het
Abcc2	G	A	19: 43,800,724	G273R	probably benign	Het
Adamts10	T	C	17: 33,550,609	V935A	probably benign	Het
Anapc15-ps	T	C	10: 95,673,121	D90G	probably damaging	Het
Atic	T	A	1: 71,563,788	V107E	probably benign	Het
Atp4b	T	C	8: 13,393,523	T52A	possibly damaging	Het
Cacna1h	C	T	17: 25,381,550	A1606T	probably damaging	Het
Cacng6	T	A	7: 3,434,808	Y217*	probably null	Het
Cc2d2a	T	G	5: 43,724,387		probably benign	Het
Cd226	T	A	18: 89,207,214	H78Q	probably benign	Het
Cers3	A	G	7: 66,783,418	D161G	probably damaging	Het
Ces1f	T	C	8: 93,275,389	H37R	probably benign	Het
Chek1	T	A	9: 36,712,115	N421I	possibly damaging	Het
Cma2	T	C	14: 55,972,792	Y45H	probably damaging	Het
Cmas	C	A	6: 142,775,244	Y401*	probably null	Het
Cyp2j8	A	T	4: 96,444,634	S492T	probably benign	Het
Dnah12	T	C	14: 26,709,310	S358P	probably benign	Het
Dnajc13	T	C	9: 104,201,952		probably null	Het
Ep400	A	C	5: 110,685,067		probably benign	Het
Fam209	T	A	2: 172,472,838	N82K	probably benign	Het
Fam92a	T	C	4: 12,164,095	D248G	probably damaging	Het
G3bp2	A	T	5: 92,073,197	Y20N	probably damaging	Het
Gli2	T	C	1: 118,837,649	D924G	probably benign	Het
Gm10787	T	C	10: 77,022,016		noncoding transcript	Het
Gm11568	A	G	11: 99,858,046	R26G	unknown	Het
Gm4788	A	G	1: 139,739,492	V376A	probably damaging	Het
Hivep3	T	G	4: 120,096,566	L693R	probably damaging	Het
Hook1	A	G	4: 95,993,212		probably benign	Het
Ibtk	A	C	9: 85,737,538	D116E	probably damaging	Het
Insrr	C	T	3: 87,810,981	T927I	possibly damaging	Het
Irx1	T	G	13: 71,959,628	S312R	probably benign	Het
Itga11	T	C	9: 62,752,288	Y441H	probably benign	Het
Itsn1	A	G	16: 91,899,623	D38G	possibly damaging	Het
Kat6b	G	T	14: 21,669,421	E1280D	probably benign	Het
Kcnk10	T	A	12: 98,436,301	Y293F	possibly damaging	Het
Krt74	T	A	15: 101,760,963		noncoding transcript	Het
Lars	T	G	18: 42,214,837	I974L	probably benign	Het
Limch1	A	G	5: 66,969,155	D42G	probably damaging	Het
Mau2	G	C	8: 70,042,432	T85R	probably damaging	Het
Mkrn3	A	G	7: 62,418,864	I393T	probably benign	Het
Mpl	A	C	4: 118,444,020	S541R	probably damaging	Het
Nfrkb	T	C	9: 31,410,268	S754P	possibly damaging	Het
Olfr1170	A	G	2: 88,224,474	V186A	possibly damaging	Het
Olfr1233	A	G	2: 89,340,236	L22P	probably benign	Het
Olfr1350	T	C	7: 6,570,653	Y221H	possibly damaging	Het
Olfr1537	T	A	9: 39,238,200	T75S	probably damaging	Het
P2rx7	A	T	5: 122,673,798	I391F	possibly damaging	Het
Pbrm1	T	A	14: 31,085,059		probably null	Het
Pcdh8	T	C	14: 79,770,076	D349G	probably damaging	Het
Pias1	A	G	9: 62,882,009	S639P	possibly damaging	Het
Pkhd1l1	A	T	15: 44,484,424	I232F	probably damaging	Het
Plxnc1	C	T	10: 94,837,935	R995Q	probably damaging	Het
Pnliprp2	T	A	19: 58,774,087	S375T	probably benign	Het
Prkar1b	C	T	5: 139,020,092	V313M	probably benign	Het
Ptpn13	T	C	5: 103,529,717	S734P	probably damaging	Het
Rdh1	T	C	10: 127,759,941	W2R	possibly damaging	Het
Rsph10b	A	T	5: 143,949,338	I285L	probably benign	Het
Rubcnl	T	C	14: 75,047,547	F502S	probably damaging	Het
Ryr2	T	A	13: 11,638,443	I3693F	probably damaging	Het
Ryr2	T	C	13: 11,799,861	Y675C	probably damaging	Het
Scaper	T	C	9: 55,685,923	T477A	probably benign	Het
Scn2a	G	T	2: 65,711,925	V791L	probably benign	Het
Sdk1	A	T	5: 142,132,065	T1573S	probably damaging	Het
Sema3c	A	T	5: 17,714,415	H483L	probably benign	Het
Sema6c	T	C	3: 95,168,691	S219P	probably damaging	Het
Slc10a5	T	G	3: 10,335,117	E161A	probably damaging	Het
Slc22a23	C	T	13: 34,344,383	G139S	possibly damaging	Het
Slc34a3	C	T	2: 25,233,065		probably benign	Het
Slc38a9	A	T	13: 112,729,196		probably null	Het
Taok1	A	C	11: 77,559,844	S367R	possibly damaging	Het
Tlr6	G	A	5: 64,954,860	Q235*	probably null	Het
Tpgs1	T	C	10: 79,675,782	Y253H	probably damaging	Het
Tubgcp3	T	C	8: 12,653,462	T288A	probably benign	Het
Ubr4	A	G	4: 139,426,902	E2140G	probably benign	Het
Uso1	A	G	5: 92,174,019	Q257R	probably benign	Het
Zfp106	A	G	2: 120,532,196	V48A	probably damaging	Het
Zfp174	T	A	16: 3,848,254	S128T	possibly damaging	Het
Zscan26	T	A	13: 21,445,055	D426V	probably benign	Het

Other mutations in Top2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00518:Top2a	APN	11	99018821	nonsense	probably null
IGL01285:Top2a	APN	11	99006159	splice site	probably benign
IGL01445:Top2a	APN	11	99011030	missense	probably damaging	1.00
IGL01451:Top2a	APN	11	99011030	missense	probably damaging	1.00
IGL01456:Top2a	APN	11	99011030	missense	probably damaging	1.00
IGL01458:Top2a	APN	11	99011030	missense	probably damaging	1.00
IGL01481:Top2a	APN	11	99011030	missense	probably damaging	1.00
IGL01485:Top2a	APN	11	99011030	missense	probably damaging	1.00
IGL01753:Top2a	APN	11	99007274	missense	probably damaging	0.97
IGL03029:Top2a	APN	11	99018799	missense	probably benign	0.03
PIT4581001:Top2a	UTSW	11	99002964	missense	probably damaging	0.97
PIT4585001:Top2a	UTSW	11	99001373	missense	probably benign	0.02
R0008:Top2a	UTSW	11	99002903	nonsense	probably null
R0047:Top2a	UTSW	11	98997856	missense	probably benign
R0047:Top2a	UTSW	11	98997856	missense	probably benign
R0070:Top2a	UTSW	11	99015060	critical splice acceptor site	probably null
R0070:Top2a	UTSW	11	99015060	critical splice acceptor site	probably null
R0116:Top2a	UTSW	11	99003590	missense	probably benign	0.00
R0245:Top2a	UTSW	11	99010096	missense	probably benign	0.37
R0276:Top2a	UTSW	11	99009907	splice site	probably benign
R0288:Top2a	UTSW	11	99016423	splice site	probably benign
R0335:Top2a	UTSW	11	99022955	missense	probably benign	0.08
R0422:Top2a	UTSW	11	99009853	missense	probably damaging	1.00
R0546:Top2a	UTSW	11	98999226	missense	possibly damaging	0.75
R0599:Top2a	UTSW	11	99001417	missense	probably damaging	0.99
R0727:Top2a	UTSW	11	99012148	nonsense	probably null
R1565:Top2a	UTSW	11	99001054	missense	probably damaging	0.99
R1674:Top2a	UTSW	11	99009273	missense	probably damaging	0.96
R1844:Top2a	UTSW	11	99016069	missense	probably benign	0.06
R1959:Top2a	UTSW	11	98995977	splice site	probably null
R2124:Top2a	UTSW	11	99004228	missense	probably benign	0.00
R2128:Top2a	UTSW	11	99009807	missense	probably damaging	0.97
R3707:Top2a	UTSW	11	98996825	missense	probably benign	0.13
R4110:Top2a	UTSW	11	99022960	missense	probably damaging	1.00
R4112:Top2a	UTSW	11	99022960	missense	probably damaging	1.00
R4423:Top2a	UTSW	11	99001405	missense	probably benign	0.00
R4425:Top2a	UTSW	11	99001405	missense	probably benign	0.00
R4914:Top2a	UTSW	11	99002960	missense	probably damaging	1.00
R4939:Top2a	UTSW	11	99010092	missense	probably damaging	1.00
R4944:Top2a	UTSW	11	98997850	missense	probably benign	0.37
R4971:Top2a	UTSW	11	98993841	missense	probably damaging	1.00
R5362:Top2a	UTSW	11	99018912	missense	probably damaging	1.00
R5477:Top2a	UTSW	11	99016480	nonsense	probably null
R5499:Top2a	UTSW	11	99022376	missense	probably benign	0.20
R5911:Top2a	UTSW	11	99016465	missense	possibly damaging	0.92
R7126:Top2a	UTSW	11	99014992	missense	probably benign	0.09
R7131:Top2a	UTSW	11	99004182	missense	possibly damaging	0.75
R7174:Top2a	UTSW	11	99024096	start gained	probably benign
R7329:Top2a	UTSW	11	99004246	missense	possibly damaging	0.57
R7560:Top2a	UTSW	11	99000837	missense	probably benign
R7563:Top2a	UTSW	11	99016179	missense	probably damaging	1.00
R7740:Top2a	UTSW	11	98993814	missense	probably benign	0.34
R7841:Top2a	UTSW	11	99022350	missense	probably damaging	1.00
R7894:Top2a	UTSW	11	99009605	missense	probably damaging	1.00
R8122:Top2a	UTSW	11	98999167	missense	probably benign
R8260:Top2a	UTSW	11	99000769	missense	probably null	0.87
R8504:Top2a	UTSW	11	99014741	missense	probably benign
R8550:Top2a	UTSW	11	98995918	missense	probably benign
U24488:Top2a	UTSW	11	99022426	missense	probably damaging	1.00
X0025:Top2a	UTSW	11	98995941	missense	probably benign	0.32

Predicted Primers

PCR Primer
(F):5'- TCTTAAAGCCCGCTACCCGCTA -3'
(R):5'- AGCCCCATTACAGTGTGTGAGGAA -3'

Sequencing Primer
(F):5'- TTGTCGAGGAGGGACATCAA -3'
(R):5'- gtttgatttccccagcacc -3'

Posted On

2013-06-11