Mutagenetix > Incidental Mutation

Incidental Mutation 'R7670:Top2b'

592118

Institutional Source

Beutler Lab

Gene Symbol

Top2b

Ensembl Gene

ENSMUSG00000017485

Gene Name

topoisomerase (DNA) II beta

Synonyms

D230016L12Rik, Top-2

MMRRC Submission

045742-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.888) question?

Stock #

R7670 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

16365179-16435462 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 16416620 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 1127 (S1127P)

Ref Sequence

ENSEMBL: ENSMUSP00000017629 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000017629] [ENSMUST00000161693]

AlphaFold

Q64511

Predicted Effect

possibly damaging
Transcript: ENSMUST00000017629
AA Change: S1127P

PolyPhen 2 Score 0.605 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000017629
Gene: ENSMUSG00000017485
AA Change: S1127P

Domain	Start	End	E-Value	Type
Blast:TOP2c	32	70	7e-10	BLAST
HATPase_c	85	234	1.91e-2	SMART
TOP2c	89	679	N/A	SMART
TOP4c	702	1175	2.55e-230	SMART
low complexity region	1201	1215	N/A	INTRINSIC
low complexity region	1287	1299	N/A	INTRINSIC
low complexity region	1324	1336	N/A	INTRINSIC
low complexity region	1360	1382	N/A	INTRINSIC
Pfam:DTHCT	1495	1597	4.6e-31	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000160501
AA Change: S173P

PolyPhen 2 Score 0.966 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000124889
Gene: ENSMUSG00000017485
AA Change: S173P

Domain	Start	End	E-Value	Type
TOP4c	2	222	3.97e-12	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000161693
AA Change: S66P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000123992
Gene: ENSMUSG00000017485
AA Change: S66P

Domain	Start	End	E-Value	Type
Pfam:DNA_topoisoIV	1	117	1.2e-12	PFAM
low complexity region	161	173	N/A	INTRINSIC
low complexity region	198	210	N/A	INTRINSIC
low complexity region	234	256	N/A	INTRINSIC

Meta Mutation Damage Score

0.0749

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.4%

Validation Efficiency

100% (62/62)

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, beta, is localized to chromosome 3 and the alpha form is localized to chromosome 17. 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
PHENOTYPE: Homozygous null mice exhibit abnormal innervation. Offspring die shortly after birth due to respiratory failure. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930435E12Rik	C	T	16: 38,828,091 (GRCm38)	D219N	possibly damaging	Het
Adam26a	T	A	8: 43,570,153 (GRCm38)	H100L	probably benign	Het
Adgrf2	T	C	17: 42,711,372 (GRCm38)	N187S	probably damaging	Het
Adipoq	T	A	16: 23,157,582 (GRCm38)	H244Q	probably damaging	Het
Arhgap40	T	A	2: 158,531,925 (GRCm38)	S209T	probably benign	Het
Arrdc3	C	T	13: 80,889,093 (GRCm38)	L123F	probably damaging	Het
Aspscr1	A	G	11: 120,689,039 (GRCm38)	N212D	probably benign	Het
Ccr9	A	T	9: 123,779,306 (GRCm38)	S18C	probably damaging	Het
Cdc42bpa	T	A	1: 180,065,081 (GRCm38)	V270D	probably damaging	Het
Clic4	A	G	4: 135,217,205 (GRCm38)	Y220H	probably damaging	Het
Cntln	A	C	4: 84,979,340 (GRCm38)	H388P	possibly damaging	Het
Col12a1	A	G	9: 79,631,643 (GRCm38)	V2457A	probably damaging	Het
Ctsk	A	G	3: 95,501,614 (GRCm38)	N103D	probably benign	Het
Ddx60	T	C	8: 61,975,792 (GRCm38)	S779P	probably damaging	Het
Dnah5	T	A	15: 28,246,232 (GRCm38)		probably null	Het
Dnah7b	T	A	1: 46,109,302 (GRCm38)	D279E	probably benign	Het
Fam117a	A	G	11: 95,378,834 (GRCm38)	N308S	probably benign	Het
Fasn	A	G	11: 120,813,419 (GRCm38)	V1419A	probably damaging	Het
Fhad1	A	G	4: 141,951,491 (GRCm38)	S625P	probably benign	Het
Gemin5	A	G	11: 58,147,928 (GRCm38)	V585A	probably benign	Het
Gm5145	C	A	17: 20,570,384 (GRCm38)	P8Q	probably benign	Het
Gm8332	T	C	12: 88,249,754 (GRCm38)	N116S	probably benign	Het
Herc1	C	A	9: 66,416,347 (GRCm38)	T1381K	probably damaging	Het
Herc6	T	C	6: 57,660,122 (GRCm38)	I824T	probably damaging	Het
Klrb1	C	T	6: 128,710,087 (GRCm38)	V161I	probably benign	Het
Krtap31-1	A	G	11: 99,908,432 (GRCm38)	N154D	not run	Het
Lcp1	A	T	14: 75,200,431 (GRCm38)	I94F	probably benign	Het
Lin7a	A	T	10: 107,382,691 (GRCm38)	Q154L	possibly damaging	Het
Lnx1	T	C	5: 74,685,690 (GRCm38)	Y33C	probably damaging	Het
Myo5b	T	C	18: 74,701,446 (GRCm38)	V859A	probably benign	Het
Ncbp1	A	G	4: 46,170,015 (GRCm38)	Q696R	probably damaging	Het
Neurl1b	C	G	17: 26,438,746 (GRCm38)	H219Q	probably benign	Het
Nme8	T	C	13: 19,658,829 (GRCm38)	E392G	probably benign	Het
Nufip1	CAAAACAGAAAACAGAAAAC	CAAAACAGAAAACAGAAAACAGAAAAC	14: 76,111,974 (GRCm38)		probably null	Het
Nuggc	A	G	14: 65,613,526 (GRCm38)	I298V	probably damaging	Het
Nup155	A	C	15: 8,153,696 (GRCm38)	K1247Q	probably damaging	Het
Olfr368	A	T	2: 37,331,759 (GRCm38)	E4V	probably benign	Het
Olfr403	A	G	11: 74,196,207 (GRCm38)	K235E	probably damaging	Het
Otud4	T	A	8: 79,655,864 (GRCm38)		probably null	Het
Pcdhb18	T	C	18: 37,491,696 (GRCm38)	V693A	probably damaging	Het
Pcnx3	A	G	19: 5,677,182 (GRCm38)	F1108L	probably benign	Het
Prkca	A	T	11: 108,014,344 (GRCm38)	N189K	probably damaging	Het
Rbm24	A	G	13: 46,429,207 (GRCm38)	I201V	probably benign	Het
Reep6	T	C	10: 80,333,793 (GRCm38)	L105P	probably damaging	Het
Retreg1	T	C	15: 25,941,040 (GRCm38)		probably benign	Het
Rev3l	C	T	10: 39,836,722 (GRCm38)	T2382I	probably benign	Het
Rnf31	A	G	14: 55,594,361 (GRCm38)	N230S	probably benign	Het
Rreb1	T	C	13: 37,931,572 (GRCm38)	L969P	probably benign	Het
Rsph4a	T	A	10: 33,909,033 (GRCm38)	N313K	probably damaging	Het
Serpina3f	T	A	12: 104,217,266 (GRCm38)	L129Q	probably damaging	Het
Slc9a2	T	A	1: 40,718,997 (GRCm38)	V232D	probably damaging	Het
Stmn2	T	C	3: 8,554,865 (GRCm38)	L121P	probably damaging	Het
Svep1	C	T	4: 58,097,424 (GRCm38)	G1373D	probably damaging	Het
Tmem206	A	G	1: 191,340,868 (GRCm38)	N162S	probably benign	Het
Tns1	C	A	1: 73,952,477 (GRCm38)	R1014L	possibly damaging	Het
Txndc16	A	T	14: 45,135,867 (GRCm38)	C768*	probably null	Het
Ubl7	A	T	9: 57,929,769 (GRCm38)	E354D	probably benign	Het
Ush2a	T	C	1: 188,784,708 (GRCm38)	L3205P	possibly damaging	Het
Xirp2	A	G	2: 67,510,573 (GRCm38)	T1053A	possibly damaging	Het
Zbtb21	A	G	16: 97,951,877 (GRCm38)	L402P	probably damaging	Het
Zfp27	T	A	7: 29,894,796 (GRCm38)	K581N	possibly damaging	Het
Zfp62	A	T	11: 49,215,076 (GRCm38)		probably benign	Het

Other mutations in Top2b

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00430:Top2b	APN	14	16,422,692 (GRCm38)	missense	probably benign	0.00
IGL00730:Top2b	APN	14	16,389,831 (GRCm38)	missense	probably damaging	1.00
IGL00917:Top2b	APN	14	16,407,354 (GRCm38)	missense	probably benign	0.05
IGL01959:Top2b	APN	14	16,422,695 (GRCm38)	missense	probably benign	0.19
IGL02019:Top2b	APN	14	16,409,965 (GRCm38)	missense	probably benign	0.44
IGL02119:Top2b	APN	14	16,406,733 (GRCm38)	missense	probably damaging	1.00
IGL02136:Top2b	APN	14	16,407,103 (GRCm38)	unclassified	probably benign
IGL02148:Top2b	APN	14	16,400,488 (GRCm38)	missense	probably damaging	1.00
IGL02496:Top2b	APN	14	16,387,335 (GRCm38)	missense	probably benign
IGL02503:Top2b	APN	14	16,407,163 (GRCm38)	missense	possibly damaging	0.92
IGL02672:Top2b	APN	14	16,409,166 (GRCm38)	unclassified	probably benign
IGL02721:Top2b	APN	14	16,409,236 (GRCm38)	missense	probably damaging	1.00
IGL02886:Top2b	APN	14	16,365,688 (GRCm38)	missense	possibly damaging	0.73
IGL03252:Top2b	APN	14	16,393,163 (GRCm38)	missense	possibly damaging	0.60
PIT4434001:Top2b	UTSW	14	16,423,780 (GRCm38)	critical splice donor site	probably null
R0092:Top2b	UTSW	14	16,409,263 (GRCm38)	missense	probably damaging	1.00
R0201:Top2b	UTSW	14	16,383,174 (GRCm38)	missense	probably damaging	1.00
R0390:Top2b	UTSW	14	16,418,442 (GRCm38)	missense	probably benign	0.00
R0394:Top2b	UTSW	14	16,413,556 (GRCm38)	splice site	probably null
R1159:Top2b	UTSW	14	16,430,329 (GRCm38)	missense	possibly damaging	0.81
R1424:Top2b	UTSW	14	16,383,177 (GRCm38)	missense	probably damaging	1.00
R1519:Top2b	UTSW	14	16,408,953 (GRCm38)	splice site	probably null
R1561:Top2b	UTSW	14	16,398,993 (GRCm38)	missense	possibly damaging	0.80
R1713:Top2b	UTSW	14	16,409,823 (GRCm38)	missense	probably benign	0.05
R1987:Top2b	UTSW	14	16,398,916 (GRCm38)	missense	probably damaging	0.99
R2219:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R2287:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R2422:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R2679:Top2b	UTSW	14	16,413,947 (GRCm38)	missense	probably damaging	1.00
R3687:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R3707:Top2b	UTSW	14	16,388,447 (GRCm38)	missense	probably damaging	1.00
R3810:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R3812:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R3815:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R3816:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R3818:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4023:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4025:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4026:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4133:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4157:Top2b	UTSW	14	16,384,491 (GRCm38)	missense	probably benign	0.42
R4179:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4180:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4300:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4376:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4377:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4492:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4549:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4550:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4581:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4582:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4628:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4630:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4667:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4668:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4669:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R4698:Top2b	UTSW	14	16,387,331 (GRCm38)	nonsense	probably null
R4769:Top2b	UTSW	14	16,398,991 (GRCm38)	missense	probably damaging	1.00
R4809:Top2b	UTSW	14	16,383,125 (GRCm38)	missense	probably benign	0.06
R4899:Top2b	UTSW	14	16,387,313 (GRCm38)	missense	probably damaging	1.00
R5035:Top2b	UTSW	14	16,409,966 (GRCm38)	missense	probably benign	0.01
R5621:Top2b	UTSW	14	16,387,280 (GRCm38)	missense	probably damaging	1.00
R5631:Top2b	UTSW	14	16,409,882 (GRCm38)	missense	probably damaging	1.00
R5685:Top2b	UTSW	14	16,413,666 (GRCm38)	missense	probably damaging	1.00
R5732:Top2b	UTSW	14	16,400,106 (GRCm38)	missense	possibly damaging	0.92
R5939:Top2b	UTSW	14	16,422,786 (GRCm38)	missense	probably damaging	0.96
R6007:Top2b	UTSW	14	16,423,779 (GRCm38)	critical splice donor site	probably null
R6087:Top2b	UTSW	14	16,409,864 (GRCm38)	missense	probably benign	0.14
R6144:Top2b	UTSW	14	16,423,740 (GRCm38)	missense	possibly damaging	0.48
R6196:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R6218:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R6229:Top2b	UTSW	14	16,409,838 (GRCm38)	missense	probably damaging	1.00
R6249:Top2b	UTSW	14	16,399,006 (GRCm38)	missense	probably damaging	1.00
R6337:Top2b	UTSW	14	16,399,026 (GRCm38)	missense	possibly damaging	0.77
R6353:Top2b	UTSW	14	16,416,671 (GRCm38)	missense	probably damaging	1.00
R6512:Top2b	UTSW	14	16,409,854 (GRCm38)	missense	possibly damaging	0.94
R6573:Top2b	UTSW	14	16,398,991 (GRCm38)	missense	probably damaging	1.00
R6614:Top2b	UTSW	14	16,407,142 (GRCm38)	nonsense	probably null
R6844:Top2b	UTSW	14	16,429,383 (GRCm38)	missense	possibly damaging	0.94
R6848:Top2b	UTSW	14	16,409,958 (GRCm38)	missense	possibly damaging	0.89
R6871:Top2b	UTSW	14	16,409,189 (GRCm38)	missense	probably damaging	1.00
R6895:Top2b	UTSW	14	16,413,604 (GRCm38)	missense	probably benign	0.06
R7162:Top2b	UTSW	14	16,416,653 (GRCm38)	missense	probably benign	0.00
R7247:Top2b	UTSW	14	16,416,962 (GRCm38)	missense	probably benign	0.08
R7250:Top2b	UTSW	14	16,420,411 (GRCm38)	missense	probably benign
R7359:Top2b	UTSW	14	16,407,376 (GRCm38)	missense	probably null	1.00
R7365:Top2b	UTSW	14	16,416,649 (GRCm38)	missense	probably benign	0.04
R7493:Top2b	UTSW	14	16,416,605 (GRCm38)	missense	probably benign	0.00
R7528:Top2b	UTSW	14	16,395,427 (GRCm38)	nonsense	probably null
R7562:Top2b	UTSW	14	16,412,946 (GRCm38)	missense	probably benign	0.04
R7594:Top2b	UTSW	14	16,428,587 (GRCm38)	missense	probably benign
R7894:Top2b	UTSW	14	16,413,081 (GRCm38)	missense	possibly damaging	0.68
R8031:Top2b	UTSW	14	16,412,986 (GRCm38)	missense	probably damaging	0.98
R8150:Top2b	UTSW	14	16,393,291 (GRCm38)	missense	probably damaging	0.99
R8214:Top2b	UTSW	14	16,383,177 (GRCm38)	missense	probably damaging	1.00
R8299:Top2b	UTSW	14	16,386,123 (GRCm38)	missense	possibly damaging	0.68
R8977:Top2b	UTSW	14	16,393,239 (GRCm38)	missense	probably benign	0.36
R9562:Top2b	UTSW	14	16,365,718 (GRCm38)	missense	probably benign	0.09
R9565:Top2b	UTSW	14	16,365,718 (GRCm38)	missense	probably benign	0.09
R9798:Top2b	UTSW	14	16,389,845 (GRCm38)	missense	probably damaging	1.00
X0028:Top2b	UTSW	14	16,384,499 (GRCm38)	nonsense	probably null
Z1176:Top2b	UTSW	14	16,395,434 (GRCm38)	missense	probably damaging	1.00
Z1177:Top2b	UTSW	14	16,416,953 (GRCm38)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- CCTGAAGGAGTAGCATTAACAGTAC -3'
(R):5'- GAGATCATTAACCTCTCGCCCC -3'

Sequencing Primer
(F):5'- GCATTAACAGTACAGCATTTAAGCC -3'
(R):5'- TCGCCCCTACAATTGAAAGAGAGAG -3'

Posted On

2019-11-12