Incidental Mutation 'R4133:Top2b'
ID 314768
Institutional Source Beutler Lab
Gene Symbol Top2b
Ensembl Gene ENSMUSG00000017485
Gene Name topoisomerase (DNA) II beta
Synonyms Top-2, D230016L12Rik
MMRRC Submission 041637-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.924) question?
Stock # R4133 (G1)
Quality Score 225
Status Validated
Chromosome 14
Chromosomal Location 6038976-6104585 bp(-) (GRCm39)
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
TOP4c 1 177 4.06e-6 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000160501
SMART Domains Protein: ENSMUSP00000124889
Gene: ENSMUSG00000017485

DomainStartEndE-ValueType
TOP4c 2 222 3.97e-12 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000161693
SMART Domains Protein: ENSMUSP00000123992
Gene: ENSMUSG00000017485

DomainStartEndE-ValueType
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 question?
Coding Region Coverage
  • 1x: 99.4%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.5%
Validation Efficiency 97% (77/79)
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: 75 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700036A12Rik T A 9: 60,677,280 (GRCm39) noncoding transcript Het
Aldh3b1 A G 19: 3,970,808 (GRCm39) I184T probably damaging Het
Arhgap42 C T 9: 9,011,300 (GRCm39) probably benign Het
Arhgef4 A G 1: 34,845,185 (GRCm39) D1463G probably damaging Het
Arpc5 A G 1: 152,644,622 (GRCm39) T52A probably benign Het
Asb6 A G 2: 30,718,247 (GRCm39) probably benign Het
Ash1l T C 3: 88,889,567 (GRCm39) V482A probably benign Het
Bop1 T C 15: 76,338,535 (GRCm39) N469S probably benign Het
Btaf1 T A 19: 36,939,138 (GRCm39) N266K probably benign Het
Btla T C 16: 45,059,661 (GRCm39) Y122H probably damaging Het
Cacna1g A G 11: 94,323,370 (GRCm39) M1278T probably damaging Het
Cdc42bpb A G 12: 111,287,976 (GRCm39) S524P probably benign Het
Cep78 A G 19: 15,946,519 (GRCm39) S438P probably damaging Het
Clca4a T G 3: 144,675,113 (GRCm39) E171D probably benign Het
Cldn6 A T 17: 23,900,467 (GRCm39) I144F probably damaging Het
Cpd G A 11: 76,705,644 (GRCm39) Q363* probably null Het
Cpn1 G A 19: 43,974,723 (GRCm39) P2L possibly damaging Het
Ddx31 A G 2: 28,748,864 (GRCm39) D264G probably damaging Het
Ddx39b C T 17: 35,472,065 (GRCm39) S368L probably damaging Het
Ddx60 A G 8: 62,425,254 (GRCm39) K681E probably damaging Het
Dennd1c A C 17: 57,383,980 (GRCm39) W15G possibly damaging Het
Dgkd T G 1: 87,869,223 (GRCm39) probably null Het
Dnah7c G T 1: 46,705,150 (GRCm39) A2388S probably benign Het
Etv4 C A 11: 101,661,324 (GRCm39) K442N probably damaging Het
Fam234a T C 17: 26,432,532 (GRCm39) D539G probably damaging Het
Fancm A G 12: 65,167,304 (GRCm39) T1538A probably benign Het
Fbn2 A T 18: 58,229,034 (GRCm39) N725K possibly damaging Het
Fcer2a T A 8: 3,741,130 (GRCm39) N4I possibly damaging Het
Fgd5 T C 6: 92,046,418 (GRCm39) V1229A probably damaging Het
Garin4 A T 1: 190,895,205 (GRCm39) N479K probably benign Het
Gm5471 A T 15: 44,835,297 (GRCm39) noncoding transcript Het
Gm5478 T A 15: 101,553,080 (GRCm39) I331F probably damaging Het
Gm6729 C A 10: 86,377,030 (GRCm39) noncoding transcript Het
Hectd4 G T 5: 121,415,897 (GRCm39) probably null Het
Hspb3 A C 13: 113,800,027 (GRCm39) M1R probably null Het
Igkv10-95 T C 6: 68,657,601 (GRCm39) V19A probably damaging Het
Il1rap A G 16: 26,541,636 (GRCm39) S626G probably benign Het
Ints9 A G 14: 65,228,003 (GRCm39) H103R probably benign Het
Itga4 T A 2: 79,152,996 (GRCm39) D894E probably damaging Het
Khsrp T C 17: 57,332,605 (GRCm39) H225R probably benign Het
Lama1 T C 17: 68,057,650 (GRCm39) Y575H probably damaging Het
Lama1 A T 17: 68,119,481 (GRCm39) I2653F probably damaging Het
Map4k5 A T 12: 69,892,497 (GRCm39) L144Q probably damaging Het
Mcm5 A G 8: 75,842,482 (GRCm39) Y252C probably damaging Het
Mmgt2 A G 11: 62,555,877 (GRCm39) E75G probably damaging Het
Mroh2a A T 1: 88,182,687 (GRCm39) N1205I possibly damaging Het
Nckap5 A G 1: 126,150,443 (GRCm39) V162A probably benign Het
Nr3c2 T C 8: 77,636,378 (GRCm39) I493T probably damaging Het
Or2ag16 A C 7: 106,352,286 (GRCm39) L103R probably damaging Het
Or2t46 A T 11: 58,471,901 (GRCm39) Y77F probably damaging Het
Or9s15 T C 1: 92,524,465 (GRCm39) F75L probably benign Het
Papola A G 12: 105,765,917 (GRCm39) T6A possibly damaging Het
Ppp1cc G A 5: 122,306,289 (GRCm39) R36Q probably benign Het
Ptpro G T 6: 137,397,370 (GRCm39) W81C probably damaging Het
Rasgrf2 A G 13: 92,130,773 (GRCm39) S162P possibly damaging Het
Rpusd2 T C 2: 118,869,196 (GRCm39) S540P probably damaging Het
Scn5a T A 9: 119,315,438 (GRCm39) T1757S probably damaging Het
Setbp1 T C 18: 78,900,206 (GRCm39) I1154V probably benign Het
Sirt1 T C 10: 63,171,438 (GRCm39) I209V probably null Het
Slco6c1 T A 1: 97,009,218 (GRCm39) I406L probably benign Het
Smc2 A G 4: 52,450,947 (GRCm39) E255G probably damaging Het
Snap91 C A 9: 86,659,102 (GRCm39) G477V probably damaging Het
Speg A G 1: 75,404,548 (GRCm39) Q2780R probably benign Het
Spmap2 T C 10: 79,415,884 (GRCm39) T236A probably damaging Het
Ssh2 A G 11: 77,312,095 (GRCm39) Y196C probably damaging Het
Ssxb9 A T X: 8,235,845 (GRCm39) T18S probably damaging Het
Stxbp5l T C 16: 37,028,481 (GRCm39) I527M possibly damaging Het
Tex10 T C 4: 48,468,968 (GRCm39) Y69C probably damaging Het
Thoc3 T C 13: 54,616,361 (GRCm39) D87G probably benign Het
Trps1 T C 15: 50,694,783 (GRCm39) K213R probably damaging Het
Uggt1 A T 1: 36,197,240 (GRCm39) L1221Q probably damaging Het
Vmn2r3 T A 3: 64,183,138 (GRCm39) Y187F probably damaging Het
Washc2 G A 6: 116,235,891 (GRCm39) E1121K probably damaging Het
Zfx T C X: 93,124,464 (GRCm39) N360D probably damaging Het
Znhit3 A G 11: 84,807,139 (GRCm39) V10A probably benign Het
Other mutations in Top2b
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- CACCATGGAGAAGTAAGCACTG -3'
(R):5'- TTTGAAGTACTCTCCCTGAGC -3'

Sequencing Primer
(F):5'- GCACTGAAGATGGGATCAACTG -3'
(R):5'- TCTCCCTGAGCAGAAAAACTAAATG -3'
Posted On 2015-05-14