Incidental Mutation 'R0047:Top2a'
| ID |
15929 |
| 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 |
038341-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.970)
|
| Stock # |
R0047 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
98883769-98915015 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 98888682 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Isoleucine to Leucine
at position 1260
(I1260L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000068896
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000068031]
|
| AlphaFold |
Q01320 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000068031
AA Change: I1260L
PolyPhen 2
Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
|
| SMART Domains |
Protein: ENSMUSP00000068896
Gene: ENSMUSG00000020914
AA Change: I1260L
| Domain | Start | End | E-Value | Type |
|---|
|
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: ENSMUST00000139460
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000151997
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000154332
|
| Meta Mutation Damage Score |
0.0898 |
| Coding Region Coverage |
- 1x: 89.2%
- 3x: 86.3%
- 10x: 78.8%
- 20x: 65.9%
|
| Validation Efficiency |
95% (110/116) |
| 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: 71 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1110002E22Rik |
A |
G |
3: 137,772,025 (GRCm39) |
T405A |
probably damaging |
Het |
| Acer1 |
A |
T |
17: 57,262,624 (GRCm39) |
D175E |
possibly damaging |
Het |
| Adamts9 |
G |
A |
6: 92,882,287 (GRCm39) |
|
probably benign |
Het |
| Amigo3 |
T |
C |
9: 107,931,857 (GRCm39) |
S427P |
probably benign |
Het |
| Arid4a |
T |
G |
12: 71,122,193 (GRCm39) |
L858W |
probably damaging |
Het |
| Bbox1 |
A |
G |
2: 110,098,647 (GRCm39) |
F310S |
probably damaging |
Het |
| Bltp1 |
T |
A |
3: 36,962,341 (GRCm39) |
L481M |
possibly damaging |
Het |
| Bmper |
T |
A |
9: 23,317,982 (GRCm39) |
C534S |
probably damaging |
Het |
| Cacna1d |
T |
G |
14: 30,068,747 (GRCm39) |
|
probably benign |
Het |
| Capn12 |
G |
A |
7: 28,589,812 (GRCm39) |
|
probably null |
Het |
| Chchd1 |
T |
C |
14: 20,754,231 (GRCm39) |
S48P |
possibly damaging |
Het |
| Cnot7 |
A |
G |
8: 40,948,962 (GRCm39) |
|
probably benign |
Het |
| Cux1 |
T |
C |
5: 136,392,107 (GRCm39) |
|
probably benign |
Het |
| Cyp2b19 |
T |
A |
7: 26,466,251 (GRCm39) |
D351E |
probably benign |
Het |
| Dctn1 |
G |
T |
6: 83,159,614 (GRCm39) |
G31* |
probably null |
Het |
| Duox1 |
T |
A |
2: 122,177,122 (GRCm39) |
|
probably benign |
Het |
| Egflam |
T |
G |
15: 7,282,911 (GRCm39) |
E382A |
possibly damaging |
Het |
| Ext1 |
T |
C |
15: 53,208,542 (GRCm39) |
N73S |
probably benign |
Het |
| Glg1 |
A |
T |
8: 111,892,214 (GRCm39) |
M866K |
probably damaging |
Het |
| Gm3333 |
A |
G |
13: 62,422,285 (GRCm39) |
|
noncoding transcript |
Het |
| Golm1 |
T |
A |
13: 59,792,914 (GRCm39) |
H197L |
probably benign |
Het |
| Gtse1 |
A |
G |
15: 85,746,579 (GRCm39) |
K132E |
probably damaging |
Het |
| Gxylt2 |
A |
T |
6: 100,710,339 (GRCm39) |
|
probably benign |
Het |
| Hrc |
T |
A |
7: 44,986,113 (GRCm39) |
S421R |
probably benign |
Het |
| Ighg2c |
T |
A |
12: 113,251,788 (GRCm39) |
|
probably benign |
Het |
| Ihh |
A |
G |
1: 74,985,750 (GRCm39) |
I245T |
probably benign |
Het |
| Ilf3 |
T |
A |
9: 21,300,010 (GRCm39) |
M65K |
possibly damaging |
Het |
| Kif9 |
A |
G |
9: 110,314,106 (GRCm39) |
I33V |
probably benign |
Het |
| Lama1 |
A |
T |
17: 68,102,181 (GRCm39) |
|
probably benign |
Het |
| Lamb1 |
T |
C |
12: 31,328,600 (GRCm39) |
I188T |
possibly damaging |
Het |
| Lpp |
T |
A |
16: 24,480,550 (GRCm39) |
|
probably benign |
Het |
| Mark2 |
A |
C |
19: 7,260,942 (GRCm39) |
|
probably benign |
Het |
| Mmp3 |
T |
C |
9: 7,451,910 (GRCm39) |
|
probably benign |
Het |
| Mthfd1l |
T |
A |
10: 3,928,727 (GRCm39) |
|
probably benign |
Het |
| Mtr |
A |
T |
13: 12,237,112 (GRCm39) |
S569T |
probably damaging |
Het |
| Myh13 |
T |
A |
11: 67,258,063 (GRCm39) |
S1752T |
probably benign |
Het |
| Myo5a |
T |
A |
9: 75,063,489 (GRCm39) |
L565H |
probably damaging |
Het |
| Numa1 |
A |
G |
7: 101,658,660 (GRCm39) |
K296E |
probably damaging |
Het |
| Obi1 |
T |
A |
14: 104,740,780 (GRCm39) |
|
probably null |
Het |
| Or51ab3 |
A |
T |
7: 103,201,529 (GRCm39) |
Y179F |
probably damaging |
Het |
| Or5ac19 |
C |
T |
16: 59,089,574 (GRCm39) |
G152D |
probably damaging |
Het |
| Or5b120 |
A |
G |
19: 13,479,953 (GRCm39) |
E82G |
probably benign |
Het |
| Pla2g2c |
T |
C |
4: 138,470,901 (GRCm39) |
|
probably benign |
Het |
| Pnpla7 |
A |
T |
2: 24,901,618 (GRCm39) |
E548V |
probably damaging |
Het |
| Ppm1m |
C |
A |
9: 106,073,895 (GRCm39) |
E273* |
probably null |
Het |
| Ppp2r1b |
C |
T |
9: 50,772,873 (GRCm39) |
R117* |
probably null |
Het |
| Psg-ps1 |
A |
G |
7: 17,411,806 (GRCm39) |
|
noncoding transcript |
Het |
| Rabgap1l |
G |
A |
1: 160,059,359 (GRCm39) |
|
probably benign |
Het |
| Rapgef6 |
T |
A |
11: 54,437,204 (GRCm39) |
M49K |
possibly damaging |
Het |
| Rtel1 |
T |
G |
2: 180,965,198 (GRCm39) |
I146M |
probably damaging |
Het |
| Sdr9c7 |
A |
T |
10: 127,739,541 (GRCm39) |
M219L |
probably benign |
Het |
| Serpinb1a |
A |
T |
13: 33,034,259 (GRCm39) |
L44Q |
probably damaging |
Het |
| Slc13a4 |
A |
G |
6: 35,264,297 (GRCm39) |
I190T |
possibly damaging |
Het |
| Slc46a2 |
A |
G |
4: 59,914,392 (GRCm39) |
L177P |
probably damaging |
Het |
| Slc47a2 |
C |
T |
11: 61,227,068 (GRCm39) |
V167M |
possibly damaging |
Het |
| Snrnp200 |
C |
T |
2: 127,076,874 (GRCm39) |
|
probably benign |
Het |
| Snx13 |
C |
A |
12: 35,151,123 (GRCm39) |
|
probably benign |
Het |
| Snx25 |
C |
T |
8: 46,494,402 (GRCm39) |
A828T |
probably damaging |
Het |
| Spic |
A |
G |
10: 88,511,803 (GRCm39) |
L151P |
probably damaging |
Het |
| Sptb |
G |
T |
12: 76,669,724 (GRCm39) |
Q535K |
probably damaging |
Het |
| Ssu2 |
G |
A |
6: 112,351,781 (GRCm39) |
H315Y |
probably damaging |
Het |
| Stk32a |
T |
C |
18: 43,446,443 (GRCm39) |
|
probably benign |
Het |
| Tcaf2 |
A |
G |
6: 42,606,547 (GRCm39) |
I469T |
probably benign |
Het |
| Tln2 |
A |
G |
9: 67,147,954 (GRCm39) |
|
probably benign |
Het |
| Treml1 |
C |
A |
17: 48,672,008 (GRCm39) |
S91* |
probably null |
Het |
| Trmt11 |
T |
C |
10: 30,411,239 (GRCm39) |
N418S |
probably benign |
Het |
| Ttf1 |
A |
G |
2: 28,974,667 (GRCm39) |
Y801C |
probably damaging |
Het |
| Usp34 |
C |
T |
11: 23,414,403 (GRCm39) |
A2782V |
probably benign |
Het |
| Vps4a |
T |
C |
8: 107,763,333 (GRCm39) |
L29P |
probably damaging |
Het |
| Wdfy3 |
A |
G |
5: 102,091,899 (GRCm39) |
I480T |
probably damaging |
Het |
| Ywhag |
A |
T |
5: 135,940,153 (GRCm39) |
V147E |
probably damaging |
Het |
|
| Other mutations in Top2a |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
|
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 |
|
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 |
|
| Protein Function and Prediction |
DNA Topoisomerase II alpha (Top2a) encodes a DNA topoisomerase that, through an association with the pol II holoenzyme, controls the topologic states of DNA in both prokaryotes and eukaryotes and is required for chromatin-dependent coactivation (1). In eukaryote cells, Top2a catalyzes the relaxation of supercoiled DNA, catenation, decatenation, knotting, and unknotting of circular DNA. In mouse, Top2a is abundant in testis and spleen (2). Top2a expression varies throughout the cell cycle, with highest expression in G2/M; the level of Top2a mRNA is determined by a cell cycle-regulated promoter (3). Treatment of mouse zygotes with Top2a-targeted antisense oligodeoxynucleotides led to arrest at the 2-cell stage, indicating that Top2a is essential for preimplantation development (4).
|
| References |
|
| Posted On |
2013-01-08 |
| Science Writer |
Anne Murray |
Incidental Mutation