Mutagenetix > Incidental Mutation

Incidental Mutation 'R5685:Top2b'

443305

Institutional Source

Beutler Lab

Gene Symbol

Top2b

Ensembl Gene

ENSMUSG00000017485

Gene Name

topoisomerase (DNA) II beta

Synonyms

D230016L12Rik, Top-2

Accession Numbers

Essential gene?

Probably essential (E-score: 0.888) question?

Stock #

R5685 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

16365179-16435462 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 16413666 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tryptophan to Arginine at position 1045 (W1045R)

Ref Sequence

ENSEMBL: ENSMUSP00000017629 (fasta)

Gene Model

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

AlphaFold

Q64511

Predicted Effect

probably damaging
Transcript: ENSMUST00000017629
AA Change: W1045R

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000017629
Gene: ENSMUSG00000017485
AA Change: W1045R

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

noncoding transcript
Transcript: ENSMUST00000159302

SMART Domains

Protein: ENSMUSP00000123789
Gene: ENSMUSG00000017485

Domain	Start	End	E-Value	Type
TOP4c	1	177	4.06e-6	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000160501

SMART Domains

Protein: ENSMUSP00000124889
Gene: ENSMUSG00000017485

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

Predicted Effect

probably benign
Transcript: ENSMUST00000161693

SMART Domains

Protein: ENSMUSP00000123992
Gene: ENSMUSG00000017485

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

Coding Region Coverage

1x: 99.6%
3x: 98.8%
10x: 97.0%
20x: 94.1%

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 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: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700028J19Rik	T	A	7: 44,230,550 (GRCm38)		probably benign	Het
4921501E09Rik	T	A	17: 33,066,772 (GRCm38)	H352L	probably benign	Het
Abcb5	A	T	12: 118,932,613 (GRCm38)		probably null	Het
Abcg1	G	T	17: 31,098,286 (GRCm38)	E191*	probably null	Het
Als2	A	G	1: 59,179,091 (GRCm38)	Y1263H	possibly damaging	Het
Amer2	T	A	14: 60,379,577 (GRCm38)	L281*	probably null	Het
Anxa6	T	C	11: 54,996,370 (GRCm38)	N361D	probably benign	Het
Ap1g1	A	T	8: 109,837,783 (GRCm38)	N320I	probably damaging	Het
Aqr	T	C	2: 114,156,265 (GRCm38)	D208G	possibly damaging	Het
Arnt2	T	C	7: 84,263,265 (GRCm38)	T545A	probably benign	Het
Aspm	G	A	1: 139,487,288 (GRCm38)	V2701I	probably benign	Het
Atad2	A	G	15: 58,116,798 (GRCm38)	V106A	possibly damaging	Het
Bbs2	A	C	8: 94,087,433 (GRCm38)	F186V	probably damaging	Het
Catsperg2	G	A	7: 29,701,188 (GRCm38)	P247L	probably damaging	Het
Cfap57	G	T	4: 118,569,459 (GRCm38)	Q1098K	probably benign	Het
Cxcr6	A	G	9: 123,810,746 (GRCm38)	T271A	probably benign	Het
Dock1	A	G	7: 134,772,362 (GRCm38)	E579G	probably benign	Het
Frem3	A	G	8: 80,695,303 (GRCm38)	T2111A	probably damaging	Het
Galnt1	A	T	18: 24,264,529 (GRCm38)	D229V	possibly damaging	Het
Gbp2b	A	C	3: 142,608,158 (GRCm38)	M400L	probably benign	Het
Gm1123	T	A	9: 99,009,433 (GRCm38)		probably null	Het
Gtpbp6	T	C	5: 110,104,939 (GRCm38)	H349R	probably damaging	Het
Hyal5	A	G	6: 24,876,692 (GRCm38)	K188R	probably benign	Het
Insrr	T	C	3: 87,800,496 (GRCm38)		probably null	Het
Kcnn1	A	T	8: 70,852,730 (GRCm38)	C322S	probably damaging	Het
Kdelr1	GTCTA	G	7: 45,881,617 (GRCm38)		probably null	Het
Kif23	T	C	9: 61,945,409 (GRCm38)	T8A	probably benign	Het
Lrrk2	A	T	15: 91,803,301 (GRCm38)	R2198*	probably null	Het
Mcl1	T	G	3: 95,659,798 (GRCm38)	D177E	possibly damaging	Het
Mrps11	A	T	7: 78,791,880 (GRCm38)	T137S	probably benign	Het
Mtbp	A	G	15: 55,562,772 (GRCm38)	Y90C	probably damaging	Het
Nkpd1	C	T	7: 19,523,573 (GRCm38)	Q276*	probably null	Het
Nxt1	G	T	2: 148,675,753 (GRCm38)	W138L	possibly damaging	Het
Olfr1042	T	C	2: 86,159,795 (GRCm38)	T192A	probably damaging	Het
Olfr1102	T	A	2: 87,002,277 (GRCm38)	S103T	probably benign	Het
Olfr183	T	A	16: 59,000,346 (GRCm38)	F220L	probably benign	Het
Osbpl7	C	A	11: 97,060,277 (GRCm38)	P478H	probably damaging	Het
Pitpna	T	A	11: 75,620,269 (GRCm38)	F222I	probably damaging	Het
Plekhh2	A	T	17: 84,569,882 (GRCm38)	R552W	probably damaging	Het
Plxnb2	C	T	15: 89,167,032 (GRCm38)	R328H	probably damaging	Het
Pmaip1	C	T	18: 66,460,984 (GRCm38)	T65I	probably benign	Het
Ppil4	T	G	10: 7,798,422 (GRCm38)	I110S	probably damaging	Het
Prpf38a	A	G	4: 108,570,154 (GRCm38)		probably null	Het
Psme4	G	A	11: 30,809,837 (GRCm38)	G320D	probably damaging	Het
Rab17	C	A	1: 90,958,957 (GRCm38)	R191L	probably benign	Het
Rhag	A	T	17: 40,831,331 (GRCm38)	M222L	possibly damaging	Het
Rims2	A	T	15: 39,437,206 (GRCm38)	H111L	possibly damaging	Het
Setx	T	C	2: 29,171,280 (GRCm38)	Y2234H	probably damaging	Het
Slc2a8	T	C	2: 32,981,789 (GRCm38)	I51V	possibly damaging	Het
Slc34a1	T	C	13: 55,401,272 (GRCm38)		probably null	Het
Slf1	T	C	13: 77,083,479 (GRCm38)	T594A	possibly damaging	Het
Sox6	A	T	7: 115,579,157 (GRCm38)		probably null	Het
Spata13	C	T	14: 60,691,203 (GRCm38)	S70L	probably benign	Het
Stard13	A	G	5: 151,063,127 (GRCm38)	I188T	possibly damaging	Het
Stard9	A	G	2: 120,705,322 (GRCm38)	D4020G	probably damaging	Het
Tdp1	A	G	12: 99,902,352 (GRCm38)	K255R	possibly damaging	Het
Tns2	G	T	15: 102,107,103 (GRCm38)	A124S	probably benign	Het
Trav12-2	T	C	14: 53,616,665 (GRCm38)	V32A	probably damaging	Het
Vps13c	G	T	9: 67,963,173 (GRCm38)	R3198L	possibly damaging	Het
Wee1	TCCCC	TCCC	7: 110,124,569 (GRCm38)		probably null	Het
Zfp52	T	A	17: 21,561,751 (GRCm38)	S620R	probably benign	Het
Zfp62	T	A	11: 49,216,217 (GRCm38)	C378*	probably null	Het
Zfp638	C	A	6: 83,929,987 (GRCm38)	P378H	probably damaging	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
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
R7670:Top2b	UTSW	14	16,416,620 (GRCm38)	missense	possibly damaging	0.61
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'- AAGTGGTTTCAGGGGTAGTACATATTC -3'
(R):5'- GGGTCAGATTCATAACCTCTCTG -3'

Sequencing Primer
(F):5'- GTAGGTACTCTTTGATCATATGG -3'
(R):5'- ACCTCTCTGGACTAACATTTGAATC -3'

Posted On

2016-11-09