Incidental Mutation 'R6919:Top3a'
ID 539517
Institutional Source Beutler Lab
Gene Symbol Top3a
Ensembl Gene ENSMUSG00000002814
Gene Name topoisomerase (DNA) III alpha
Synonyms Top IIIa
MMRRC Submission 045039-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6919 (G1)
Quality Score 225.009
Status Validated
Chromosome 11
Chromosomal Location 60630884-60668191 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 60640319 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 460 (I460F)
Ref Sequence ENSEMBL: ENSMUSP00000099729 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000002891] [ENSMUST00000102668] [ENSMUST00000117743] [ENSMUST00000120417]
AlphaFold O70157
Predicted Effect probably damaging
Transcript: ENSMUST00000002891
AA Change: I460F

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000002891
Gene: ENSMUSG00000002814
AA Change: I460F

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: I460F

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000099729
Gene: ENSMUSG00000002814
AA Change: I460F

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: I435F

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000113057
Gene: ENSMUSG00000002814
AA Change: I435F

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: I435F

PolyPhen 2 Score 0.125 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000113653
Gene: ENSMUSG00000002814
AA Change: I435F

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
Meta Mutation Damage Score 0.8048 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.3%
  • 20x: 97.8%
Validation Efficiency 99% (84/85)
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: 83 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700086D15Rik A G 11: 65,043,356 (GRCm39) probably benign Het
6430548M08Rik T C 8: 120,872,221 (GRCm39) S50P probably damaging Het
Aacs A G 5: 125,583,227 (GRCm39) D261G probably benign Het
Abcc4 T A 14: 118,832,306 (GRCm39) T775S probably benign Het
Acsl6 A G 11: 54,232,582 (GRCm39) probably null Het
Agbl5 T A 5: 31,062,061 (GRCm39) F196I probably benign Het
Ahnak2 T C 12: 112,741,118 (GRCm39) T985A possibly damaging Het
Ak1 A T 2: 32,521,134 (GRCm39) D101V possibly damaging Het
Alx1 A G 10: 102,861,061 (GRCm39) Y156H probably damaging Het
Angptl7 T A 4: 148,584,488 (GRCm39) S87C probably benign Het
Ankrd36 A G 11: 5,579,299 (GRCm39) T188A probably benign Het
Arhgap11a A C 2: 113,670,054 (GRCm39) S356R possibly damaging Het
Ascc3 G T 10: 50,521,849 (GRCm39) E455* probably null Het
Atp6v0a2 G A 5: 124,789,225 (GRCm39) probably null Het
B3gnt7 T C 1: 86,233,416 (GRCm39) W104R probably damaging Het
Bbs9 G A 9: 22,723,840 (GRCm39) probably null Het
Cc2d2a T A 5: 43,860,557 (GRCm39) D544E probably benign Het
Cic C T 7: 24,971,202 (GRCm39) T311I probably benign Het
Cngb1 T A 8: 95,975,003 (GRCm39) R1157W probably null Het
Cntln A G 4: 85,033,605 (GRCm39) H1310R probably benign Het
Cntnap5c A T 17: 58,600,948 (GRCm39) I764F probably benign Het
Col26a1 T C 5: 136,773,088 (GRCm39) Q362R possibly damaging Het
Cyp2c29 G A 19: 39,279,585 (GRCm39) R100K probably benign Het
D17H6S53E C G 17: 35,346,222 (GRCm39) D44E probably damaging Het
Dap3 A G 3: 88,838,296 (GRCm39) V65A probably damaging Het
Dna2 A T 10: 62,792,782 (GRCm39) I266F probably damaging Het
Dnah14 G A 1: 181,412,631 (GRCm39) G57E probably benign Het
Dock9 A T 14: 121,880,564 (GRCm39) V333E probably benign Het
Dpm1 A G 2: 168,072,195 (GRCm39) Y27H probably damaging Het
Dsp A T 13: 38,351,631 (GRCm39) Y150F possibly damaging Het
Emilin3 A T 2: 160,750,018 (GRCm39) I577N probably damaging Het
Erap1 A G 13: 74,819,552 (GRCm39) T189A probably benign Het
Fat2 A G 11: 55,173,597 (GRCm39) I2372T possibly damaging Het
Fbn2 A T 18: 58,257,259 (GRCm39) probably null Het
Gnl1 A T 17: 36,298,425 (GRCm39) R390* probably null Het
Hivep1 A G 13: 42,336,928 (GRCm39) I2336V probably benign Het
Il17rb C G 14: 29,726,228 (GRCm39) probably null Het
Itga9 T C 9: 118,716,883 (GRCm39) W396R probably damaging Het
Katnal2 A G 18: 77,098,734 (GRCm39) V152A probably benign Het
Kcnk3 A G 5: 30,779,744 (GRCm39) T265A probably benign Het
Klhl1 T C 14: 96,374,030 (GRCm39) Y672C probably benign Het
Leng8 C A 7: 4,146,625 (GRCm39) N412K possibly damaging Het
Lrrc9 T A 12: 72,553,167 (GRCm39) F1356L probably benign Het
Map7 A G 10: 20,046,828 (GRCm39) probably benign Het
Mei1 T C 15: 81,966,131 (GRCm39) F251S probably damaging Het
Mia2 A G 12: 59,176,681 (GRCm39) E9G possibly damaging Het
Ms4a13 C A 19: 11,149,249 (GRCm39) W182C probably benign Het
Muc16 C T 9: 18,571,595 (GRCm39) R308K unknown Het
Or4c103 G A 2: 88,514,028 (GRCm39) T16I possibly damaging Het
Or8g22 A G 9: 38,958,827 (GRCm39) probably benign Het
Pcnt A G 10: 76,221,632 (GRCm39) V1998A probably benign Het
Pgm2 A T 5: 64,254,368 (GRCm39) N51I probably benign Het
Piezo1 T A 8: 123,217,020 (GRCm39) H1333L probably damaging Het
Prg2 G A 2: 84,813,600 (GRCm39) V199M probably damaging Het
Prss51 T C 14: 64,334,937 (GRCm39) V182A probably damaging Het
Psmb9 A T 17: 34,402,199 (GRCm39) Y132* probably null Het
Ralyl T C 3: 13,842,091 (GRCm39) Y76H probably damaging Het
Rnaset2a A T 17: 8,349,114 (GRCm39) D174E probably benign Het
Rnft1 G A 11: 86,386,156 (GRCm39) probably null Het
Robo2 T C 16: 73,758,755 (GRCm39) Y676C probably damaging Het
Samd9l T G 6: 3,376,313 (GRCm39) Y316S possibly damaging Het
Siah3 T A 14: 75,693,578 (GRCm39) F28Y possibly damaging Het
Slc28a3 C T 13: 58,721,257 (GRCm39) probably null Het
Slc8a1 A G 17: 81,696,301 (GRCm39) F911S probably damaging Het
Spata31e2 T C 1: 26,722,015 (GRCm39) Y1055C probably benign Het
Speg T A 1: 75,364,552 (GRCm39) L156* probably null Het
Spopl T G 2: 23,407,873 (GRCm39) M269L probably benign Het
Tacr1 C T 6: 82,534,054 (GRCm39) T360I probably benign Het
Tasor T A 14: 27,171,758 (GRCm39) L397* probably null Het
Tmem262 A G 19: 6,130,767 (GRCm39) E95G probably benign Het
Tmem68 G T 4: 3,569,669 (GRCm39) T7N possibly damaging Het
Trafd1 G A 5: 121,522,137 (GRCm39) R5* probably null Het
Trim16 T A 11: 62,731,695 (GRCm39) V435D possibly damaging Het
Tspan17 A G 13: 54,943,846 (GRCm39) D236G probably damaging Het
Tssk2 A T 16: 17,717,565 (GRCm39) M323L probably benign Het
Ubqln5 A G 7: 103,778,215 (GRCm39) V203A probably benign Het
Utrn A T 10: 12,569,214 (GRCm39) L1134* probably null Het
Vmn1r37 C T 6: 66,708,704 (GRCm39) S73F possibly damaging Het
Vps13c A G 9: 67,834,734 (GRCm39) K1688E probably damaging Het
Zbtb39 A G 10: 127,577,711 (GRCm39) D95G probably damaging Het
Zfhx3 T A 8: 109,527,160 (GRCm39) I1019N probably damaging Het
Zfp207 C T 11: 80,286,329 (GRCm39) probably benign Het
Zmiz1 C T 14: 25,644,062 (GRCm39) T169M probably damaging 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
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
R7690:Top3a UTSW 11 60,647,206 (GRCm39) missense probably damaging 1.00
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'- TCAGATCAGTTGTCCTCAGGCTC -3'
(R):5'- AGGAGCCATGGGTTCTGTTC -3'

Sequencing Primer
(F):5'- TCCATCAGGAGTCACAGGCTG -3'
(R):5'- CTCACAGTGGCGTAAATCAAGTTG -3'
Posted On 2018-11-06