Incidental Mutation 'R4971:Top2a'
ID 384462
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 042566-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.970) question?
Stock # R4971 (G1)
Quality Score 225
Status Not validated
Chromosome 11
Chromosomal Location 98883769-98915015 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 98884667 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 1517 (Y1517C)
Ref Sequence ENSEMBL: ENSMUSP00000068896 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000068031]
AlphaFold Q01320
Predicted Effect probably damaging
Transcript: ENSMUST00000068031
AA Change: Y1517C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000068896
Gene: ENSMUSG00000020914
AA Change: Y1517C

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: ENSMUST00000139460
Predicted Effect noncoding transcript
Transcript: ENSMUST00000154332
Coding Region Coverage
  • 1x: 99.0%
  • 3x: 98.1%
  • 10x: 95.6%
  • 20x: 89.7%
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, 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: 57 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2ml1 A T 6: 128,524,190 (GRCm39) F1147L probably damaging Het
Abca2 T C 2: 25,332,006 (GRCm39) S1373P probably damaging Het
Abca9 A T 11: 110,042,874 (GRCm39) S392T probably benign Het
Abcd2 T C 15: 91,047,313 (GRCm39) D580G probably benign Het
Actl9 T A 17: 33,652,882 (GRCm39) L314H probably damaging Het
Adamtsl1 T C 4: 86,255,168 (GRCm39) F746L probably damaging Het
Anks6 C T 4: 47,030,795 (GRCm39) G601S probably damaging Het
Cdkl3 T C 11: 51,901,995 (GRCm39) V68A possibly damaging Het
Cnot1 A G 8: 96,448,254 (GRCm39) F2266S probably damaging Het
Colq T C 14: 31,267,034 (GRCm39) R159G probably damaging Het
Ctse A T 1: 131,592,130 (GRCm39) D152V probably damaging Het
Cul7 G T 17: 46,970,045 (GRCm39) M1011I probably benign Het
Cyb5r4 G T 9: 86,939,224 (GRCm39) V336L possibly damaging Het
Dync2h1 A T 9: 7,131,949 (GRCm39) H1619Q probably benign Het
Eif2ak1 A G 5: 143,818,986 (GRCm39) K216E probably damaging Het
F5 A T 1: 164,021,755 (GRCm39) H1410L probably benign Het
Frem2 T C 3: 53,446,604 (GRCm39) Y2388C probably damaging Het
Fsip2 C T 2: 82,816,222 (GRCm39) T3985M probably benign Het
Gak T C 5: 108,744,672 (GRCm39) Y535C probably damaging Het
Gzmc G T 14: 56,469,826 (GRCm39) P158Q probably damaging Het
Hook3 A G 8: 26,572,607 (GRCm39) Y135H probably benign Het
Ikbke GCC G 1: 131,203,004 (GRCm39) probably null Het
Ing4 A T 6: 125,020,961 (GRCm39) M28L probably benign Het
Irs3 T A 5: 137,642,754 (GRCm39) D228V probably damaging Het
Jade1 T A 3: 41,555,836 (GRCm39) I301N probably damaging Het
Kif13b T A 14: 64,995,011 (GRCm39) M921K possibly damaging Het
Kmt2c A G 5: 25,515,870 (GRCm39) S2658P probably benign Het
Map3k4 A G 17: 12,468,382 (GRCm39) probably null Het
Map4k5 C T 12: 69,899,493 (GRCm39) V53I possibly damaging Het
Mdn1 T C 4: 32,739,827 (GRCm39) S3694P probably damaging Het
Mroh7 A G 4: 106,548,749 (GRCm39) V1038A probably benign Het
Muc5ac T C 7: 141,370,015 (GRCm39) V3185A possibly damaging Het
Mup5 T A 4: 61,751,297 (GRCm39) N117I probably benign Het
Myo19 T A 11: 84,783,023 (GRCm39) M179K probably damaging Het
Myo1c A G 11: 75,562,414 (GRCm39) Y902C probably damaging Het
Nf1 T A 11: 79,335,469 (GRCm39) I977K probably damaging Het
Nos1 T C 5: 118,081,899 (GRCm39) V1240A probably benign Het
Nr3c1 T C 18: 39,619,930 (GRCm39) D119G probably damaging Het
Oga C A 19: 45,758,485 (GRCm39) probably null Het
Or4c107 A T 2: 88,788,863 (GRCm39) N18Y probably damaging Het
Pdlim2 A G 14: 70,405,208 (GRCm39) V219A probably damaging Het
Pira13 T A 7: 3,825,805 (GRCm39) M355L probably benign Het
Polr1g T C 7: 19,091,487 (GRCm39) N207D probably benign Het
Prdx1 T C 4: 116,549,128 (GRCm39) probably null Het
Rbfox1 C T 16: 7,111,952 (GRCm39) R173C probably damaging Het
Rbp3 T A 14: 33,676,427 (GRCm39) V125D probably damaging Het
Resf1 T C 6: 149,227,097 (GRCm39) probably benign Het
Rhot1 T A 11: 80,124,300 (GRCm39) I154K probably damaging Het
Runx1t1 C T 4: 13,837,978 (GRCm39) R129C probably damaging Het
Setbp1 A G 18: 78,901,382 (GRCm39) S762P probably benign Het
Slc13a3 A G 2: 165,290,619 (GRCm39) I67T probably damaging Het
Tbc1d2b A T 9: 90,100,923 (GRCm39) M689K probably benign Het
Txndc2 A T 17: 65,945,849 (GRCm39) N109K probably damaging Het
Tyk2 A G 9: 21,031,797 (GRCm39) probably null Het
Wdfy3 A T 5: 102,096,838 (GRCm39) L320* probably null Het
Zfp456 T C 13: 67,514,995 (GRCm39) E237G probably benign Het
Zscan10 A G 17: 23,826,147 (GRCm39) E103G possibly damaging 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
R4425: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
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'- CGACAGCATGTTACAGAGAGC -3'
(R):5'- TGCGACTCTTGCTTTGGACC -3'

Sequencing Primer
(F):5'- CATGTTACAGAGAGCAAAGCTG -3'
(R):5'- CTTACTACTTAGTAGAAGAAGGTGGG -3'
Posted On 2016-04-27