Incidental Mutation 'R4628:Top2b'
ID 348989
Institutional Source Beutler Lab
Gene Symbol Top2b
Ensembl Gene ENSMUSG00000017485
Gene Name topoisomerase (DNA) II beta
Synonyms Top-2, D230016L12Rik
MMRRC Submission 041893-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.924) question?
Stock # R4628 (G1)
Quality Score 225
Status Not 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: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.3%
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: 81 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca7 G T 10: 79,851,022 (GRCm39) probably null Het
Abcb4 A G 5: 8,957,399 (GRCm39) D176G probably benign Het
Adamts18 C T 8: 114,499,800 (GRCm39) W371* probably null Het
Akr1c13 G T 13: 4,247,869 (GRCm39) V214F probably damaging Het
Alkbh2 C T 5: 114,262,287 (GRCm39) E148K probably damaging Het
Ankrd12 T C 17: 66,292,989 (GRCm39) T815A probably benign Het
Arid3a T C 10: 79,766,992 (GRCm39) S89P possibly damaging Het
Ass1 A T 2: 31,371,000 (GRCm39) D63V probably damaging Het
Atxn3 T A 12: 101,889,337 (GRCm39) probably benign Het
Bcap29 C T 12: 31,676,806 (GRCm39) S88N probably benign Het
Bsn G T 9: 107,990,434 (GRCm39) P1773T probably damaging Het
Ccdc141 A G 2: 76,890,024 (GRCm39) S423P probably benign Het
Cfap46 A T 7: 139,260,843 (GRCm39) L85Q probably damaging Het
Chd8 T C 14: 52,444,372 (GRCm39) R438G probably benign Het
Chd9 T A 8: 91,710,091 (GRCm39) M289K probably benign Het
Col14a1 T A 15: 55,313,229 (GRCm39) Y26* probably null Het
Colec10 A G 15: 54,323,127 (GRCm39) T117A possibly damaging Het
Colq C A 14: 31,265,979 (GRCm39) G178V probably damaging Het
Defb3 A T 8: 19,345,156 (GRCm39) R37S probably benign Het
Duox1 A G 2: 122,176,733 (GRCm39) Y1418C probably damaging Het
Engase C T 11: 118,375,731 (GRCm39) S33F probably damaging Het
Erich3 A T 3: 154,469,324 (GRCm39) T1259S probably damaging Het
Fam98c T C 7: 28,854,693 (GRCm39) T49A possibly damaging Het
Fhod3 T A 18: 25,253,186 (GRCm39) F1379I possibly damaging Het
Fndc3b T C 3: 27,610,277 (GRCm39) I86V probably benign Het
Gm1123 A G 9: 98,896,289 (GRCm39) V197A probably damaging Het
Gm4847 A T 1: 166,457,964 (GRCm39) V463E probably damaging Het
Gm9772 T C 17: 22,226,188 (GRCm39) K32R probably damaging Het
Gm9804 T C 12: 49,448,540 (GRCm39) S161P unknown Het
Gpr162 C T 6: 124,838,405 (GRCm39) D82N probably benign Het
Grid2ip T C 5: 143,368,630 (GRCm39) V650A probably damaging Het
Hs1bp3 T C 12: 8,386,357 (GRCm39) V253A probably benign Het
Hsd3b6 T G 3: 98,713,895 (GRCm39) K135Q possibly damaging Het
Igfn1 T C 1: 135,887,468 (GRCm39) D2532G possibly damaging Het
Iqgap2 A G 13: 95,899,837 (GRCm39) Y74H probably benign Het
Itga2 A G 13: 115,014,229 (GRCm39) V233A probably benign Het
Kat14 A G 2: 144,246,140 (GRCm39) probably benign Het
Kctd21 A G 7: 96,996,782 (GRCm39) D85G probably damaging Het
Kera A G 10: 97,445,493 (GRCm39) N284S probably benign Het
Krt1 C T 15: 101,754,622 (GRCm39) G543S unknown Het
Lcmt1 T A 7: 123,010,035 (GRCm39) C183* probably null Het
Lcn5 A G 2: 25,548,075 (GRCm39) E28G possibly damaging Het
Leo1 A T 9: 75,352,979 (GRCm39) D174V probably damaging Het
Llgl1 A T 11: 60,600,811 (GRCm39) T636S probably damaging Het
Lrrc8e T A 8: 4,283,981 (GRCm39) C69S probably damaging Het
Maml3 A T 3: 51,703,891 (GRCm39) probably benign Het
Maz G T 7: 126,624,519 (GRCm39) H334N possibly damaging Het
Mcm6 T C 1: 128,279,285 (GRCm39) D167G probably benign Het
Mrpl24 A C 3: 87,829,436 (GRCm39) probably null Het
Myo18a G A 11: 77,714,962 (GRCm39) V834M probably damaging Het
Neb T A 2: 52,198,362 (GRCm39) R461* probably null Het
Notch4 C A 17: 34,789,159 (GRCm39) T486N probably damaging Het
Nphp3 A G 9: 103,880,257 (GRCm39) E93G probably damaging Het
Nup188 A G 2: 30,219,358 (GRCm39) Y858C probably damaging Het
Or13a17 T A 7: 140,271,291 (GRCm39) S158T probably benign Het
Or13a28 C T 7: 140,218,297 (GRCm39) R228C probably benign Het
Or1j11 T A 2: 36,311,869 (GRCm39) L153* probably null Het
Otud4 T A 8: 80,366,597 (GRCm39) D21E possibly damaging Het
Ovgp1 T A 3: 105,887,639 (GRCm39) probably null Het
Pdia3 A T 2: 121,244,620 (GRCm39) N11I possibly damaging Het
Pex5 T C 6: 124,380,079 (GRCm39) D286G possibly damaging Het
Pias3 T C 3: 96,607,136 (GRCm39) I133T probably damaging Het
Postn A G 3: 54,279,578 (GRCm39) D352G probably damaging Het
Prl7c1 T C 13: 27,962,065 (GRCm39) R81G probably benign Het
Rmi1 A G 13: 58,556,950 (GRCm39) R400G probably benign Het
Rtraf T A 14: 19,867,155 (GRCm39) N116I probably benign Het
Semp2l2a T A 8: 13,886,625 (GRCm39) R489W probably damaging Het
Slc6a12 T A 6: 121,328,951 (GRCm39) C50* probably null Het
Spring1 G C 5: 118,397,479 (GRCm39) A154P probably damaging Het
Srcin1 T A 11: 97,439,752 (GRCm39) H126L probably benign Het
Tmtc2 A T 10: 105,139,511 (GRCm39) S672T probably benign Het
Ube2c A G 2: 164,614,093 (GRCm39) N143S possibly damaging Het
Uroc1 A T 6: 90,332,310 (GRCm39) I556F probably damaging Het
Vmn1r124 T A 7: 20,994,302 (GRCm39) K81* probably null Het
Vmn1r57 T A 7: 5,223,972 (GRCm39) C166S probably damaging Het
Vmn2r114 ATTT ATT 17: 23,509,906 (GRCm39) probably null Het
Vmn2r68 A G 7: 84,883,673 (GRCm39) V144A probably benign Het
Vmn2r85 C T 10: 130,261,235 (GRCm39) M367I probably benign Het
Vwa3a T A 7: 120,392,598 (GRCm39) N812K probably benign Het
Wdfy4 A T 14: 32,824,515 (GRCm39) N1301K probably damaging Het
Zfhx4 G A 3: 5,468,536 (GRCm39) R2898H probably damaging 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
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
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'- GCACTGAAGATGGGATCAACTG -3'
(R):5'- TGAAGTACTCTCCCTGAGCAG -3'

Sequencing Primer
(F):5'- CTGAAGATGGGATCAACTGAGAACTG -3'
(R):5'- TCTCCCTGAGCAGAAAAACTAAATG -3'
Posted On 2015-10-08