Incidental Mutation 'R7690:Top3a'
ID 593347
Institutional Source Beutler Lab
Gene Symbol Top3a
Ensembl Gene ENSMUSG00000002814
Gene Name topoisomerase (DNA) III alpha
Synonyms Top IIIa
MMRRC Submission 045754-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7690 (G1)
Quality Score 225.009
Status Validated
Chromosome 11
Chromosomal Location 60630884-60668191 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 60647206 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Isoleucine at position 238 (L238I)
Ref Sequence ENSEMBL: ENSMUSP00000002891 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000002891] [ENSMUST00000102668] [ENSMUST00000117743] [ENSMUST00000120417]
AlphaFold O70157
Predicted Effect probably damaging
Transcript: ENSMUST00000002891
AA Change: L238I

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000002891
Gene: ENSMUSG00000002814
AA Change: L238I

DomainStartEndE-ValueType
TOPRIM 35 169 5.04e-24 SMART
TOP1Bc 172 269 4.99e-37 SMART
TOP1Ac 315 569 1.47e-107 SMART
Pfam:zf-C4_Topoisom 655 694 1.7e-15 PFAM
Pfam:zf-GRF 813 854 9.7e-23 PFAM
low complexity region 884 896 N/A INTRINSIC
Pfam:zf-GRF 897 941 7.9e-24 PFAM
ZnF_C2HC 985 1001 7.06e-2 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000102668
AA Change: L238I

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000099729
Gene: ENSMUSG00000002814
AA Change: L238I

DomainStartEndE-ValueType
TOPRIM 35 169 5.04e-24 SMART
TOP1Bc 172 269 4.99e-37 SMART
TOP1Ac 315 569 1.47e-107 SMART
Pfam:zf-C4_Topoisom 655 694 5.9e-16 PFAM
Pfam:zf-GRF 813 854 2.6e-21 PFAM
low complexity region 884 896 N/A INTRINSIC
Pfam:zf-GRF 897 941 4.2e-22 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000117743
AA Change: L213I

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000113057
Gene: ENSMUSG00000002814
AA Change: L213I

DomainStartEndE-ValueType
TOPRIM 10 144 5.04e-24 SMART
TOP1Bc 147 244 4.99e-37 SMART
TOP1Ac 290 544 1.47e-107 SMART
Pfam:zf-C4_Topoisom 630 669 4.6e-16 PFAM
ZnF_C2HC 755 771 7.06e-2 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000120417
AA Change: L213I

PolyPhen 2 Score 0.393 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000113653
Gene: ENSMUSG00000002814
AA Change: L213I

DomainStartEndE-ValueType
TOPRIM 10 144 5.04e-24 SMART
TOP1Bc 147 244 4.99e-37 SMART
TOP1Ac 290 544 1.47e-107 SMART
Pfam:zf-C4_Topoisom 630 666 1.9e-13 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.3%
Validation Efficiency 97% (57/59)
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 enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
PHENOTYPE: Mice homozygous for a null allele die shortly after implantation and the induction of decidual reaction. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 59 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca12 T A 1: 71,353,313 (GRCm39) T710S probably benign Het
Adgrl2 A G 3: 148,522,934 (GRCm39) L430P Het
Agap1 T C 1: 89,770,793 (GRCm39) S648P probably benign Het
Alox5 T C 6: 116,392,417 (GRCm39) H368R probably damaging Het
Ano2 T C 6: 125,990,161 (GRCm39) F761L probably damaging Het
Aox4 T C 1: 58,303,076 (GRCm39) V1169A probably damaging Het
Apbb1ip T A 2: 22,706,996 (GRCm39) M11K unknown Het
Arl5a G T 2: 52,302,077 (GRCm39) H112Q possibly damaging Het
Ccdc18 C T 5: 108,376,528 (GRCm39) T1323I probably benign Het
Cmtm5 G A 14: 55,173,938 (GRCm39) probably benign Het
Cul2 T C 18: 3,419,420 (GRCm39) Y194H probably benign Het
Daglb T C 5: 143,479,938 (GRCm39) I415T possibly damaging Het
Ddx28 A G 8: 106,736,963 (GRCm39) V365A probably damaging Het
Dnah6 T C 6: 73,146,063 (GRCm39) probably null Het
Eppk1 T A 15: 75,995,946 (GRCm39) T312S probably benign Het
Erich4 C A 7: 25,314,710 (GRCm39) V68L possibly damaging Het
Fam171a2 G A 11: 102,328,660 (GRCm39) P700S probably benign Het
Fat3 T C 9: 15,909,477 (GRCm39) N2175S probably damaging Het
Fcrl6 T G 1: 172,426,223 (GRCm39) R191S probably damaging Het
Fpgt A G 3: 154,793,467 (GRCm39) S187P probably damaging Het
Gapvd1 T G 2: 34,619,134 (GRCm39) T80P possibly damaging Het
Gclm A G 3: 122,039,705 (GRCm39) N24S probably damaging Het
Gdf15 A G 8: 71,083,997 (GRCm39) I89T possibly damaging Het
Gpn2 A G 4: 133,318,693 (GRCm39) E306G probably damaging Het
Iars2 A T 1: 185,053,194 (GRCm39) L359Q probably damaging Het
Kbtbd4 T G 2: 90,736,240 (GRCm39) C84G possibly damaging Het
Manea A G 4: 26,327,910 (GRCm39) V377A probably benign Het
Map4 C T 9: 109,828,861 (GRCm39) T82I probably damaging Het
Mocos C T 18: 24,797,082 (GRCm39) H81Y probably damaging Het
Mtx1 T A 3: 89,120,088 (GRCm39) T87S Het
Muc6 G C 7: 141,217,659 (GRCm39) P2338R probably damaging Het
Myom2 A T 8: 15,161,717 (GRCm39) probably null Het
Mzt1 C T 14: 99,278,024 (GRCm39) C48Y probably damaging Het
Nlrp9b C A 7: 19,758,295 (GRCm39) P511T probably benign Het
Noc2l A G 4: 156,322,088 (GRCm39) E135G probably benign Het
Nova1 G A 12: 46,767,549 (GRCm39) P124L unknown Het
Pax8 T A 2: 24,331,682 (GRCm39) T134S probably benign Het
Pde4a T A 9: 21,077,300 (GRCm39) L26Q probably damaging Het
Pde6b G A 5: 108,567,384 (GRCm39) E254K probably damaging Het
Pdlim7 A G 13: 55,656,744 (GRCm39) I70T probably damaging Het
Pinx1 T A 14: 64,101,660 (GRCm39) probably null Het
Pomt2 C A 12: 87,177,141 (GRCm39) R352L probably damaging Het
Rapgef5 G A 12: 117,685,105 (GRCm39) V519I possibly damaging Het
Rnps1 A G 17: 24,637,168 (GRCm39) E16G unknown Het
Slc4a5 T C 6: 83,262,854 (GRCm39) F782S probably damaging Het
Snap91 A G 9: 86,707,031 (GRCm39) V253A possibly damaging Het
Syce3 T C 15: 89,281,544 (GRCm39) M32V possibly damaging Het
Tcaf3 C A 6: 42,574,069 (GRCm39) V48L probably damaging Het
Tenm4 T C 7: 96,512,740 (GRCm39) V1366A probably benign Het
Tnxb G A 17: 34,908,494 (GRCm39) M1382I probably benign Het
Tnxb G A 17: 34,908,501 (GRCm39) G1385R probably damaging Het
Trim9 A T 12: 70,295,117 (GRCm39) N742K probably benign Het
Trp63 T A 16: 25,695,483 (GRCm39) Y482N unknown Het
Ttc23 T G 7: 67,319,918 (GRCm39) F192V possibly damaging Het
Uck1 A G 2: 32,148,184 (GRCm39) V180A probably benign Het
Vwa5b1 G A 4: 138,318,244 (GRCm39) T541I probably damaging Het
Zfp456 G T 13: 67,514,913 (GRCm39) H264Q probably damaging Het
Zfpm2 T G 15: 40,818,162 (GRCm39) V165G possibly damaging Het
Zup1 C T 10: 33,806,151 (GRCm39) probably null Het
Other mutations in Top3a
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01712:Top3a APN 11 60,652,562 (GRCm39) missense probably damaging 1.00
IGL02935:Top3a APN 11 60,653,354 (GRCm39) missense possibly damaging 0.53
R0057:Top3a UTSW 11 60,631,510 (GRCm39) missense probably benign
R0057:Top3a UTSW 11 60,631,510 (GRCm39) missense probably benign
R0369:Top3a UTSW 11 60,633,615 (GRCm39) missense probably damaging 1.00
R1171:Top3a UTSW 11 60,641,419 (GRCm39) missense probably benign 0.02
R1459:Top3a UTSW 11 60,650,188 (GRCm39) missense probably damaging 1.00
R1621:Top3a UTSW 11 60,641,433 (GRCm39) missense probably damaging 1.00
R1812:Top3a UTSW 11 60,650,188 (GRCm39) missense probably damaging 1.00
R1839:Top3a UTSW 11 60,644,714 (GRCm39) missense probably damaging 1.00
R1873:Top3a UTSW 11 60,638,810 (GRCm39) nonsense probably null
R2004:Top3a UTSW 11 60,633,315 (GRCm39) missense probably damaging 0.99
R2277:Top3a UTSW 11 60,636,700 (GRCm39) missense possibly damaging 0.95
R2406:Top3a UTSW 11 60,646,838 (GRCm39) missense probably damaging 1.00
R2418:Top3a UTSW 11 60,638,842 (GRCm39) missense possibly damaging 0.95
R3196:Top3a UTSW 11 60,650,182 (GRCm39) missense probably damaging 1.00
R3879:Top3a UTSW 11 60,634,765 (GRCm39) missense possibly damaging 0.92
R4695:Top3a UTSW 11 60,633,238 (GRCm39) missense probably benign 0.40
R4715:Top3a UTSW 11 60,633,823 (GRCm39) nonsense probably null
R4768:Top3a UTSW 11 60,653,316 (GRCm39) missense probably damaging 1.00
R4910:Top3a UTSW 11 60,643,204 (GRCm39) splice site probably benign
R5305:Top3a UTSW 11 60,653,365 (GRCm39) missense possibly damaging 0.56
R5387:Top3a UTSW 11 60,653,316 (GRCm39) missense probably damaging 1.00
R5419:Top3a UTSW 11 60,653,348 (GRCm39) missense probably damaging 1.00
R5806:Top3a UTSW 11 60,667,746 (GRCm39) critical splice donor site probably null
R6162:Top3a UTSW 11 60,636,763 (GRCm39) missense probably damaging 1.00
R6279:Top3a UTSW 11 60,640,234 (GRCm39) missense probably benign 0.02
R6300:Top3a UTSW 11 60,640,234 (GRCm39) missense probably benign 0.02
R6381:Top3a UTSW 11 60,634,849 (GRCm39) missense probably damaging 1.00
R6383:Top3a UTSW 11 60,640,285 (GRCm39) missense probably benign 0.30
R6767:Top3a UTSW 11 60,641,579 (GRCm39) missense possibly damaging 0.84
R6919:Top3a UTSW 11 60,640,319 (GRCm39) missense probably damaging 1.00
R7299:Top3a UTSW 11 60,638,974 (GRCm39) missense probably damaging 0.99
R7301:Top3a UTSW 11 60,638,974 (GRCm39) missense probably damaging 0.99
R7442:Top3a UTSW 11 60,644,744 (GRCm39) missense possibly damaging 0.66
R7786:Top3a UTSW 11 60,667,792 (GRCm39) missense probably damaging 1.00
R7792:Top3a UTSW 11 60,633,790 (GRCm39) missense probably benign
R8790:Top3a UTSW 11 60,631,363 (GRCm39) missense possibly damaging 0.87
R8818:Top3a UTSW 11 60,633,877 (GRCm39) missense probably damaging 1.00
R8867:Top3a UTSW 11 60,633,481 (GRCm39) missense probably benign 0.00
R8914:Top3a UTSW 11 60,631,405 (GRCm39) missense probably damaging 1.00
R9031:Top3a UTSW 11 60,636,695 (GRCm39) missense probably damaging 0.99
R9102:Top3a UTSW 11 60,647,155 (GRCm39) missense probably damaging 1.00
R9103:Top3a UTSW 11 60,654,253 (GRCm39) critical splice acceptor site probably null
R9130:Top3a UTSW 11 60,641,401 (GRCm39) critical splice donor site probably null
R9548:Top3a UTSW 11 60,644,768 (GRCm39) missense probably benign 0.19
R9578:Top3a UTSW 11 60,647,517 (GRCm39) missense probably damaging 0.99
R9732:Top3a UTSW 11 60,640,391 (GRCm39) missense probably benign 0.01
R9774:Top3a UTSW 11 60,638,998 (GRCm39) missense probably damaging 0.98
X0063:Top3a UTSW 11 60,641,470 (GRCm39) nonsense probably null
X0065:Top3a UTSW 11 60,654,224 (GRCm39) missense probably damaging 1.00
Z1176:Top3a UTSW 11 60,633,463 (GRCm39) missense probably benign 0.32
Z1177:Top3a UTSW 11 60,633,642 (GRCm39) missense possibly damaging 0.56
Z1186:Top3a UTSW 11 60,641,410 (GRCm39) missense probably benign
Z1187:Top3a UTSW 11 60,641,410 (GRCm39) missense probably benign
Z1188:Top3a UTSW 11 60,641,410 (GRCm39) missense probably benign
Z1189:Top3a UTSW 11 60,641,410 (GRCm39) missense probably benign
Z1190:Top3a UTSW 11 60,641,410 (GRCm39) missense probably benign
Z1191:Top3a UTSW 11 60,641,410 (GRCm39) missense probably benign
Z1192:Top3a UTSW 11 60,641,410 (GRCm39) missense probably benign
Predicted Primers PCR Primer
(F):5'- TGCATATGGGCAGGTACAGG -3'
(R):5'- ATGGAGCCAACACAGCTTC -3'

Sequencing Primer
(F):5'- GCGGGACAATAACCATGCCTTTAC -3'
(R):5'- CCAACACAGCTTCATGGTTTATGG -3'
Posted On 2019-11-12