Incidental Mutation 'R4425:Top2a'
ID 328121
Institutional Source Beutler Lab
Gene Symbol Top2a
Ensembl Gene ENSMUSG00000020914
Gene Name topoisomerase (DNA) II alpha
Synonyms DNA Topoisomerase II alpha, Top-2
MMRRC Submission 041144-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.970) question?
Stock # R4425 (G1)
Quality Score 225
Status Validated
Chromosome 11
Chromosomal Location 98883769-98915015 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 98892231 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Threonine at position 1077 (I1077T)
Ref Sequence ENSEMBL: ENSMUSP00000068896 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000068031]
AlphaFold Q01320
Predicted Effect probably benign
Transcript: ENSMUST00000068031
AA Change: I1077T

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
SMART Domains Protein: ENSMUSP00000068896
Gene: ENSMUSG00000020914
AA Change: I1077T

DomainStartEndE-ValueType
low complexity region 10 21 N/A INTRINSIC
Blast:TOP2c 22 60 3e-12 BLAST
HATPase_c 75 224 1.81e-2 SMART
TOP2c 79 669 N/A SMART
TOP4c 692 1166 3.58e-234 SMART
low complexity region 1192 1202 N/A INTRINSIC
low complexity region 1226 1238 N/A INTRINSIC
low complexity region 1261 1273 N/A INTRINSIC
low complexity region 1291 1306 N/A INTRINSIC
low complexity region 1407 1418 N/A INTRINSIC
Pfam:DTHCT 1425 1518 1.1e-18 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000104097
Predicted Effect noncoding transcript
Transcript: ENSMUST00000144318
Predicted Effect noncoding transcript
Transcript: ENSMUST00000151997
Meta Mutation Damage Score 0.0744 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.3%
Validation Efficiency 98% (55/56)
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, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. 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. [provided by RefSeq, Jul 2010]
Allele List at MGI

All alleles(47) : Targeted(1) Gene trapped(46)

Other mutations in this stock
Total: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc3 T C 11: 94,236,870 (GRCm39) T1456A probably damaging Het
Acad11 T C 9: 103,950,844 (GRCm39) F56S probably damaging Het
Adamts8 A G 9: 30,867,952 (GRCm39) N592S possibly damaging Het
Amh A G 10: 80,642,755 (GRCm39) D313G probably damaging Het
Ampd2 T C 3: 107,994,052 (GRCm39) probably benign Het
Arap3 A G 18: 38,111,653 (GRCm39) L1115P probably damaging Het
Arfgap1 C A 2: 180,622,869 (GRCm39) D327E probably benign Het
Capns2 T A 8: 93,628,252 (GRCm39) I47N possibly damaging Het
Cd163 T C 6: 124,304,862 (GRCm39) S1080P possibly damaging Het
Ceacam10 A T 7: 24,480,433 (GRCm39) Y68F possibly damaging Het
Cep44 G A 8: 56,991,652 (GRCm39) P317S probably benign Het
Cfh A T 1: 140,028,613 (GRCm39) Y688* probably null Het
Chrnb1 A T 11: 69,677,773 (GRCm39) S326R probably damaging Het
Cngb1 C T 8: 96,026,344 (GRCm39) V25M probably damaging Het
Cyp2c50 A T 19: 40,079,136 (GRCm39) N160Y possibly damaging Het
Dalrd3 T C 9: 108,448,800 (GRCm39) probably benign Het
Eef1d C A 15: 75,774,648 (GRCm39) S253I possibly damaging Het
Efl1 G A 7: 82,412,491 (GRCm39) C960Y probably damaging Het
Elmo1 C G 13: 20,784,382 (GRCm39) Y646* probably null Het
Epb41l2 C A 10: 25,382,078 (GRCm39) D701E possibly damaging Het
Fbxl4 T A 4: 22,422,699 (GRCm39) probably null Het
Fhod1 T C 8: 106,063,983 (GRCm39) probably benign Het
Gm8741 G T 17: 35,555,062 (GRCm39) noncoding transcript Het
Igkv10-95 A T 6: 68,657,606 (GRCm39) I21F probably damaging Het
Il10rb C A 16: 91,204,603 (GRCm39) N51K possibly damaging Het
Krt78 T C 15: 101,856,375 (GRCm39) T479A probably benign Het
Lrig3 T C 10: 125,849,273 (GRCm39) S998P probably benign Het
Lrrc8c T A 5: 105,755,755 (GRCm39) M510K probably benign Het
Nfrkb G T 9: 31,311,258 (GRCm39) C369F probably damaging Het
Nphp1 T C 2: 127,630,719 (GRCm39) E19G possibly damaging Het
Or10a5 A C 7: 106,635,698 (GRCm39) E112A probably damaging Het
Or4f14b T C 2: 111,775,534 (GRCm39) H89R probably benign Het
Ovol3 A T 7: 29,934,789 (GRCm39) probably null Het
Ppp1r16b C T 2: 158,599,174 (GRCm39) T382I probably benign Het
Rims2 T C 15: 39,301,320 (GRCm39) probably null Het
Sh3rf3 T C 10: 58,919,398 (GRCm39) V505A probably benign Het
Shkbp1 T C 7: 27,042,727 (GRCm39) N570S probably benign Het
Slc35f4 C T 14: 49,556,307 (GRCm39) V149I possibly damaging Het
Snx27 A G 3: 94,469,330 (GRCm39) F4L probably benign Het
Syvn1 C T 19: 6,099,951 (GRCm39) probably benign Het
Tagap1 G A 17: 7,223,511 (GRCm39) S395L probably benign Het
Tcstv2b C A 13: 120,373,908 (GRCm39) L127F probably damaging Het
Tek A G 4: 94,751,904 (GRCm39) T1014A probably damaging Het
Tpo T C 12: 30,154,015 (GRCm39) Y230C probably damaging Het
Trav12-2 A G 14: 53,854,332 (GRCm39) Q102R possibly damaging Het
Ttn G A 2: 76,733,430 (GRCm39) probably benign Het
Vmn1r183 A T 7: 23,754,973 (GRCm39) I259F probably benign Het
Vmn1r228 T C 17: 20,996,861 (GRCm39) E219G probably damaging Het
Vsig8 G T 1: 172,390,714 (GRCm39) G254V probably damaging Het
Vwa8 A G 14: 79,320,246 (GRCm39) I1086V probably benign Het
Zfp423 G A 8: 88,509,601 (GRCm39) H123Y probably damaging Het
Zfp811 A T 17: 33,016,521 (GRCm39) C506* probably null Het
Other mutations in Top2a
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00518:Top2a APN 11 98,909,647 (GRCm39) nonsense probably null
IGL01285:Top2a APN 11 98,896,985 (GRCm39) splice site probably benign
IGL01445:Top2a APN 11 98,901,856 (GRCm39) missense probably damaging 1.00
IGL01451:Top2a APN 11 98,901,856 (GRCm39) missense probably damaging 1.00
IGL01456:Top2a APN 11 98,901,856 (GRCm39) missense probably damaging 1.00
IGL01458:Top2a APN 11 98,901,856 (GRCm39) missense probably damaging 1.00
IGL01481:Top2a APN 11 98,901,856 (GRCm39) missense probably damaging 1.00
IGL01485:Top2a APN 11 98,901,856 (GRCm39) missense probably damaging 1.00
IGL01753:Top2a APN 11 98,898,100 (GRCm39) missense probably damaging 0.97
IGL03029:Top2a APN 11 98,909,625 (GRCm39) missense probably benign 0.03
PIT4581001:Top2a UTSW 11 98,893,790 (GRCm39) missense probably damaging 0.97
PIT4585001:Top2a UTSW 11 98,892,199 (GRCm39) missense probably benign 0.02
R0008:Top2a UTSW 11 98,893,729 (GRCm39) nonsense probably null
R0047:Top2a UTSW 11 98,888,682 (GRCm39) missense probably benign
R0047:Top2a UTSW 11 98,888,682 (GRCm39) missense probably benign
R0070:Top2a UTSW 11 98,905,886 (GRCm39) critical splice acceptor site probably null
R0070:Top2a UTSW 11 98,905,886 (GRCm39) critical splice acceptor site probably null
R0116:Top2a UTSW 11 98,894,416 (GRCm39) missense probably benign 0.00
R0245:Top2a UTSW 11 98,900,922 (GRCm39) missense probably benign 0.37
R0276:Top2a UTSW 11 98,900,733 (GRCm39) splice site probably benign
R0288:Top2a UTSW 11 98,907,249 (GRCm39) splice site probably benign
R0335:Top2a UTSW 11 98,913,781 (GRCm39) missense probably benign 0.08
R0422:Top2a UTSW 11 98,900,679 (GRCm39) missense probably damaging 1.00
R0546:Top2a UTSW 11 98,890,052 (GRCm39) missense possibly damaging 0.75
R0558:Top2a UTSW 11 98,887,665 (GRCm39) missense probably benign
R0599:Top2a UTSW 11 98,892,243 (GRCm39) missense probably damaging 0.99
R0727:Top2a UTSW 11 98,902,974 (GRCm39) nonsense probably null
R1565:Top2a UTSW 11 98,891,880 (GRCm39) missense probably damaging 0.99
R1674:Top2a UTSW 11 98,900,099 (GRCm39) missense probably damaging 0.96
R1844:Top2a UTSW 11 98,906,895 (GRCm39) missense probably benign 0.06
R1959:Top2a UTSW 11 98,886,803 (GRCm39) splice site probably null
R2124:Top2a UTSW 11 98,895,054 (GRCm39) missense probably benign 0.00
R2128:Top2a UTSW 11 98,900,633 (GRCm39) missense probably damaging 0.97
R3707:Top2a UTSW 11 98,887,651 (GRCm39) missense probably benign 0.13
R4110:Top2a UTSW 11 98,913,786 (GRCm39) missense probably damaging 1.00
R4112:Top2a UTSW 11 98,913,786 (GRCm39) missense probably damaging 1.00
R4423:Top2a UTSW 11 98,892,231 (GRCm39) missense probably benign 0.00
R4914:Top2a UTSW 11 98,893,786 (GRCm39) missense probably damaging 1.00
R4939:Top2a UTSW 11 98,900,918 (GRCm39) missense probably damaging 1.00
R4944:Top2a UTSW 11 98,888,676 (GRCm39) missense probably benign 0.37
R4971:Top2a UTSW 11 98,884,667 (GRCm39) missense probably damaging 1.00
R5362:Top2a UTSW 11 98,909,738 (GRCm39) missense probably damaging 1.00
R5477:Top2a UTSW 11 98,907,306 (GRCm39) nonsense probably null
R5499:Top2a UTSW 11 98,913,202 (GRCm39) missense probably benign 0.20
R5911:Top2a UTSW 11 98,907,291 (GRCm39) missense possibly damaging 0.92
R7126:Top2a UTSW 11 98,905,818 (GRCm39) missense probably benign 0.09
R7131:Top2a UTSW 11 98,895,008 (GRCm39) missense possibly damaging 0.75
R7174:Top2a UTSW 11 98,914,922 (GRCm39) start gained probably benign
R7329:Top2a UTSW 11 98,895,072 (GRCm39) missense possibly damaging 0.57
R7560:Top2a UTSW 11 98,891,663 (GRCm39) missense probably benign
R7563:Top2a UTSW 11 98,907,005 (GRCm39) missense probably damaging 1.00
R7740:Top2a UTSW 11 98,884,640 (GRCm39) missense probably benign 0.34
R7841:Top2a UTSW 11 98,913,176 (GRCm39) missense probably damaging 1.00
R7894:Top2a UTSW 11 98,900,431 (GRCm39) missense probably damaging 1.00
R8122:Top2a UTSW 11 98,889,993 (GRCm39) missense probably benign
R8260:Top2a UTSW 11 98,891,595 (GRCm39) missense probably null 0.87
R8504:Top2a UTSW 11 98,905,567 (GRCm39) missense probably benign
R8550:Top2a UTSW 11 98,886,744 (GRCm39) missense probably benign
R8558:Top2a UTSW 11 98,912,549 (GRCm39) missense probably damaging 1.00
R8693:Top2a UTSW 11 98,900,868 (GRCm39) missense probably damaging 1.00
R8851:Top2a UTSW 11 98,900,677 (GRCm39) missense probably damaging 1.00
R9143:Top2a UTSW 11 98,900,705 (GRCm39) missense probably benign 0.14
R9240:Top2a UTSW 11 98,901,368 (GRCm39) nonsense probably null
R9294:Top2a UTSW 11 98,891,904 (GRCm39) missense probably benign 0.00
R9301:Top2a UTSW 11 98,897,790 (GRCm39) missense probably damaging 0.99
R9383:Top2a UTSW 11 98,901,884 (GRCm39) nonsense probably null
R9450:Top2a UTSW 11 98,894,434 (GRCm39) missense possibly damaging 0.73
R9515:Top2a UTSW 11 98,902,970 (GRCm39) missense probably damaging 0.99
R9655:Top2a UTSW 11 98,905,334 (GRCm39) missense probably damaging 1.00
R9683:Top2a UTSW 11 98,887,683 (GRCm39) missense probably benign 0.21
R9689:Top2a UTSW 11 98,914,883 (GRCm39) missense probably benign 0.01
U24488:Top2a UTSW 11 98,913,252 (GRCm39) missense probably damaging 1.00
X0025:Top2a UTSW 11 98,886,767 (GRCm39) missense probably benign 0.32
Predicted Primers PCR Primer
(F):5'- AGTACAAACATGCAGCTTCCTTC -3'
(R):5'- TTCCCTTTTGCAGAGAGGAGG -3'

Sequencing Primer
(F):5'- ACAAACATGCAGCTTCCTTCATTTTC -3'
(R):5'- ACTCACTCTGTAGACCAGGCTG -3'
Posted On 2015-07-07