Mutagenetix > Incidental Mutation

Incidental Mutation 'R6218:Top2b'

503863

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 #

R6218 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

16365179-16435462 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 16409189 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Methionine at position 777 (I777M)

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: I777M

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000017629
Gene: ENSMUSG00000017485
AA Change: I777M

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

Meta Mutation Damage Score

0.8018

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.5%

Validation Efficiency

100% (65/65)

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: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2300003K06Rik	G	T	11: 99,837,904	Q38K	probably benign	Het
9930111J21Rik2	A	T	11: 49,019,307	N766K	probably benign	Het
Adam15	A	C	3: 89,343,883	I505S	probably benign	Het
Apc2	T	C	10: 80,306,420	M391T	probably damaging	Het
Arsi	G	A	18: 60,916,651	G202E	probably benign	Het
Bclaf1	A	G	10: 20,334,628	S840G	probably benign	Het
Cacna2d4	A	G	6: 119,239,060	Y96C	probably damaging	Het
Cald1	CAAAA	CAAA	6: 34,747,928		probably null	Het
Ddhd1	A	G	14: 45,614,176	L141P	probably damaging	Het
Dnaaf3	A	T	7: 4,523,672	S469T	probably benign	Het
Dzip3	A	T	16: 48,958,465	M323K	possibly damaging	Het
E430018J23Rik	C	T	7: 127,393,409	A10T	possibly damaging	Het
Eci2	T	A	13: 34,993,065		probably null	Het
Fam109b	T	A	15: 82,343,716	H145Q	probably benign	Het
Fam227b	A	T	2: 126,126,962	V64E	probably damaging	Het
Galnt2	A	G	8: 124,343,315	I524V	probably benign	Het
Gm10549	C	A	18: 33,464,305		probably benign	Het
Gm14548	A	T	7: 3,894,032	S602T	possibly damaging	Het
Gm3443	T	A	19: 21,555,746	S25T	probably damaging	Het
Gpr22	T	A	12: 31,711,617	K14*	probably null	Het
Grip1	T	C	10: 119,986,346	S405P	possibly damaging	Het
Helz2	C	A	2: 181,232,294	V2136L	probably benign	Het
Helz2	T	C	2: 181,235,945	H1020R	probably damaging	Het
Il1f5	G	A	2: 24,277,490		probably benign	Het
Iqsec1	T	A	6: 90,689,635	S607C	probably damaging	Het
Klhl2	A	T	8: 64,752,767	Y373*	probably null	Het
L3mbtl3	T	C	10: 26,292,747	I595V	unknown	Het
Large2	T	C	2: 92,370,636	D65G	probably damaging	Het
Lrrfip1	T	C	1: 91,082,159	Y122H	probably damaging	Het
Map1b	A	T	13: 99,433,206	D1002E	unknown	Het
Mink1	C	T	11: 70,598,894	T59I	possibly damaging	Het
Mrvi1	G	A	7: 110,876,905	T819M	probably benign	Het
Myo7b	T	C	18: 31,959,454	N2097D	probably benign	Het
Nbea	C	A	3: 55,628,484	C2893F	probably damaging	Het
Nlgn1	A	T	3: 25,436,093	V490E	probably damaging	Het
Olfr1230	G	T	2: 89,296,962	H103N	probably damaging	Het
Olfr131	A	G	17: 38,082,729	M83T	probably damaging	Het
Olfr1318	T	C	2: 112,156,356	I135T	probably damaging	Het
Olfr1369-ps1	G	A	13: 21,116,231	E180K	probably damaging	Het
Olfr730	C	A	14: 50,186,678	D180Y	probably damaging	Het
Pctp	A	G	11: 89,987,318	I130T	probably benign	Het
Pdcl3	T	C	1: 38,988,071		probably null	Het
Pkp1	T	C	1: 135,879,908	K541E	probably damaging	Het
Plekhh2	G	A	17: 84,591,564	V990I	probably benign	Het
Ppp1r3a	A	T	6: 14,718,431	V828D	probably damaging	Het
Prrc2b	T	C	2: 32,208,811	Y712H	probably damaging	Het
Prune2	T	C	19: 17,121,562	S1477P	probably benign	Het
Psma5	A	G	3: 108,279,802	K239R	probably benign	Het
Rhobtb1	G	C	10: 69,270,456	A284P	probably benign	Het
Samsn1	G	A	16: 75,945,274		noncoding transcript	Het
Scel	A	G	14: 103,572,042	T273A	probably benign	Het
Slc22a5	T	A	11: 53,891,618		probably benign	Het
Slc25a37	A	T	14: 69,249,504	M110K	possibly damaging	Het
Slc6a2	A	T	8: 92,981,981	M242L	probably benign	Het
Slc8a3	C	A	12: 81,199,567	W904L	probably benign	Het
Ss18l1	G	A	2: 180,055,112	V109I	probably benign	Het
Tbx5	C	T	5: 119,853,598	H245Y	probably damaging	Het
Thumpd2	C	A	17: 81,052,913	L244F	probably damaging	Het
Tmem107	T	A	11: 69,071,415	V66E	probably damaging	Het
Tnr	T	C	1: 159,888,314	V882A	possibly damaging	Het
Ttbk1	A	G	17: 46,470,807	V340A	possibly damaging	Het
Veph1	T	C	3: 66,255,060	E59G	probably damaging	Het
Vmn1r234	T	A	17: 21,229,721	M299K	possibly damaging	Het
Vps13b	T	C	15: 35,770,464	Y2018H	probably benign	Het
Zbtb11	A	G	16: 55,998,073	E620G	probably benign	Het
Zfp418	A	G	7: 7,182,628	H530R	possibly 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
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
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'- GCACTGAAGATGGGATCAACTG -3'
(R):5'- TTGAAGTACTCTCCCTGAGCAG -3'

Sequencing Primer
(F):5'- CTGAAGATGGGATCAACTGAGAACTG -3'
(R):5'- TCTCCCTGAGCAGAAAAACTAAATG -3'

Posted On

2018-02-27