Mutagenetix > Incidental Mutation

Incidental Mutation 'R5387:Top3a'

425349

Institutional Source

Beutler Lab

Gene Symbol

Top3a

Ensembl Gene

ENSMUSG00000002814

Gene Name

topoisomerase (DNA) III alpha

Synonyms

Top IIIa

MMRRC Submission

042959-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R5387 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

60740058-60777365 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 60762490 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 53 (F53L)

Ref Sequence

ENSEMBL: ENSMUSP00000115727 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000002891] [ENSMUST00000102668] [ENSMUST00000117743] [ENSMUST00000120417] [ENSMUST00000130068]

AlphaFold

O70157

Predicted Effect

probably damaging
Transcript: ENSMUST00000002891
AA Change: F98L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000002891
Gene: ENSMUSG00000002814
AA Change: F98L

Domain	Start	End	E-Value	Type
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: F98L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000099729
Gene: ENSMUSG00000002814
AA Change: F98L

Domain	Start	End	E-Value	Type
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: F73L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000113057
Gene: ENSMUSG00000002814
AA Change: F73L

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000120417
AA Change: F73L

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000113653
Gene: ENSMUSG00000002814
AA Change: F73L

Domain	Start	End	E-Value	Type
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

Predicted Effect

probably damaging
Transcript: ENSMUST00000130068
AA Change: F53L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000115727
Gene: ENSMUSG00000002814
AA Change: F53L

Domain	Start	End	E-Value	Type
PDB:4CGY\|A	1	85	2e-48	PDB
SCOP:d1gkub3	5	85	7e-12	SMART
Blast:TOPRIM	10	85	7e-50	BLAST

Meta Mutation Damage Score

0.6662

Coding Region Coverage

1x: 99.4%
3x: 98.8%
10x: 97.6%
20x: 96.0%

Validation Efficiency

99% (80/81)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610009B22Rik	A	T	11: 51,685,974	D32E	probably benign	Het
2210408I21Rik	T	A	13: 77,259,973	S140T	probably benign	Het
Ahnak	T	C	19: 9,003,691	S780P	probably damaging	Het
Ankhd1	C	A	18: 36,634,644	H1205N	probably damaging	Het
Ano1	T	C	7: 144,648,619	K139R	probably benign	Het
Anp32b	T	G	4: 46,468,573	C114W	probably damaging	Het
Ascl1	C	T	10: 87,492,689	A134T	probably damaging	Het
Atl2	C	T	17: 79,852,800	E453K	probably benign	Het
Aup1	C	T	6: 83,055,024	A84V	probably damaging	Het
Btbd7	A	T	12: 102,837,785	M332K	probably damaging	Het
Cacna1d	A	G	14: 30,100,751	V1107A	probably damaging	Het
Cd33	G	A	7: 43,532,053	Q114*	probably null	Het
Col4a4	C	T	1: 82,493,591	G681E	unknown	Het
Defb22	C	A	2: 152,485,906	A120S	unknown	Het
Dnah7b	A	G	1: 46,188,659	I1347M	probably damaging	Het
Efcab5	A	G	11: 77,134,842	I549T	possibly damaging	Het
Esp15	T	A	17: 39,644,577		probably null	Het
Fbxo7	A	G	10: 86,024,654	T42A	probably benign	Het
Filip1	A	G	9: 79,818,274	I1021T	probably benign	Het
Gad1	C	A	2: 70,563,851	S7*	probably null	Het
Gm281	C	A	14: 13,914,438	M1I	probably null	Het
H2-Q7	C	T	17: 35,439,542	T52M	probably damaging	Het
H2-T3	C	T	17: 36,186,702	G28R	probably benign	Het
Hist1h2ad	T	A	13: 23,574,667		probably null	Het
Idh2	TCCCAGG	T	7: 80,098,331		probably benign	Het
Ift81	A	G	5: 122,555,535	Y604H	probably damaging	Het
Igsf11	A	G	16: 39,022,423	Y154C	probably damaging	Het
Kif26b	G	T	1: 178,914,876	A846S	probably benign	Het
Lnx2	G	A	5: 147,028,154	P420S	probably benign	Het
Lrit2	A	G	14: 37,072,259	T427A	probably damaging	Het
Lrrc43	G	T	5: 123,499,671		probably null	Het
Mug1	T	C	6: 121,884,394	Y1325H	probably damaging	Het
Naglu	A	T	11: 101,076,724	Y500F	probably damaging	Het
Npy4r	A	G	14: 34,146,983	M116T	probably benign	Het
Nrd1	A	G	4: 109,039,762	Y526C	probably damaging	Het
Nrp2	T	C	1: 62,762,813	S472P	probably benign	Het
Olfr102	T	A	17: 37,314,292	T31S	probably benign	Het
Olfr361	T	C	2: 37,085,719	T10A	possibly damaging	Het
Otogl	T	A	10: 107,780,933	T1828S	probably benign	Het
Pank2	C	T	2: 131,274,262	T200I	probably benign	Het
Pbrm1	A	G	14: 31,082,610	Y946C	probably damaging	Het
Pde12	A	T	14: 26,666,453	S437T	probably benign	Het
Pikfyve	A	G	1: 65,265,268	K1710E	possibly damaging	Het
Plcd3	A	G	11: 103,078,455	S229P	probably damaging	Het
Polr3a	T	C	14: 24,454,941	I1084V	possibly damaging	Het
Prkaa2	C	A	4: 105,040,177	D280Y	probably damaging	Het
Ptprg	T	A	14: 12,153,873	S531R	probably damaging	Het
R3hdm2	T	C	10: 127,485,434	S620P	probably damaging	Het
Rab33b	A	G	3: 51,493,455	T117A	probably damaging	Het
Rasal2	T	C	1: 157,157,765	D804G	possibly damaging	Het
Rbp3	A	G	14: 33,956,413	T773A	possibly damaging	Het
Rrnad1	A	T	3: 87,930,011		probably benign	Het
Rspry1	A	G	8: 94,638,286	T185A	possibly damaging	Het
Sec61a2	G	T	2: 5,882,545		probably benign	Het
Setx	C	T	2: 29,147,594	R1364C	probably benign	Het
Shtn1	G	T	19: 59,038,369	L97M	probably damaging	Het
Slc35f1	T	C	10: 53,108,164	L340P	probably damaging	Het
Slc45a1	T	A	4: 150,643,909		probably benign	Het
Slmap	T	C	14: 26,459,933	E386G	probably benign	Het
Smc2	C	T	4: 52,475,096	A924V	probably benign	Het
Sp110	C	G	1: 85,589,118	E219D	probably damaging	Het
Tecta	G	A	9: 42,375,063	L766F	probably damaging	Het
Tle3	C	T	9: 61,407,489		probably null	Het
Trem1	T	C	17: 48,241,513	I26T	possibly damaging	Het
Ttc7b	G	T	12: 100,446,963	Q199K	possibly damaging	Het
Ubap2l	T	C	3: 90,006,596	Y975C	probably benign	Het
Ubxn11	C	A	4: 134,123,426	D196E	probably damaging	Het
Unc80	A	G	1: 66,530,021	H945R	possibly damaging	Het
Usp15	A	G	10: 123,131,286	I405T	probably damaging	Het
Uty	C	T	Y: 1,189,339	E138K	probably damaging	Het
Wapl	A	G	14: 34,677,295	E107G	probably benign	Het
Wbp1l	T	C	19: 46,644,457		probably null	Het
Zfp184	T	G	13: 21,949,640		probably benign	Het
Zfp36	A	C	7: 28,377,868	L205R	possibly damaging	Het

Other mutations in Top3a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01712:Top3a	APN	11	60761736	missense	probably damaging	1.00
IGL02935:Top3a	APN	11	60762528	missense	possibly damaging	0.53
R0057:Top3a	UTSW	11	60740684	missense	probably benign
R0057:Top3a	UTSW	11	60740684	missense	probably benign
R0369:Top3a	UTSW	11	60742789	missense	probably damaging	1.00
R1171:Top3a	UTSW	11	60750593	missense	probably benign	0.02
R1459:Top3a	UTSW	11	60759362	missense	probably damaging	1.00
R1621:Top3a	UTSW	11	60750607	missense	probably damaging	1.00
R1812:Top3a	UTSW	11	60759362	missense	probably damaging	1.00
R1839:Top3a	UTSW	11	60753888	missense	probably damaging	1.00
R1873:Top3a	UTSW	11	60747984	nonsense	probably null
R2004:Top3a	UTSW	11	60742489	missense	probably damaging	0.99
R2277:Top3a	UTSW	11	60745874	missense	possibly damaging	0.95
R2406:Top3a	UTSW	11	60756012	missense	probably damaging	1.00
R2418:Top3a	UTSW	11	60748016	missense	possibly damaging	0.95
R3196:Top3a	UTSW	11	60759356	missense	probably damaging	1.00
R3879:Top3a	UTSW	11	60743939	missense	possibly damaging	0.92
R4695:Top3a	UTSW	11	60742412	missense	probably benign	0.40
R4715:Top3a	UTSW	11	60742997	nonsense	probably null
R4768:Top3a	UTSW	11	60762490	missense	probably damaging	1.00
R4910:Top3a	UTSW	11	60752378	splice site	probably benign
R5305:Top3a	UTSW	11	60762539	missense	possibly damaging	0.56
R5419:Top3a	UTSW	11	60762522	missense	probably damaging	1.00
R5806:Top3a	UTSW	11	60776920	critical splice donor site	probably null
R6162:Top3a	UTSW	11	60745937	missense	probably damaging	1.00
R6279:Top3a	UTSW	11	60749408	missense	probably benign	0.02
R6300:Top3a	UTSW	11	60749408	missense	probably benign	0.02
R6381:Top3a	UTSW	11	60744023	missense	probably damaging	1.00
R6383:Top3a	UTSW	11	60749459	missense	probably benign	0.30
R6767:Top3a	UTSW	11	60750753	missense	possibly damaging	0.84
R6919:Top3a	UTSW	11	60749493	missense	probably damaging	1.00
R7299:Top3a	UTSW	11	60748148	missense	probably damaging	0.99
R7301:Top3a	UTSW	11	60748148	missense	probably damaging	0.99
R7442:Top3a	UTSW	11	60753918	missense	possibly damaging	0.66
R7690:Top3a	UTSW	11	60756380	missense	probably damaging	1.00
R7786:Top3a	UTSW	11	60776966	missense	probably damaging	1.00
R7792:Top3a	UTSW	11	60742964	missense	probably benign
R8790:Top3a	UTSW	11	60740537	missense	possibly damaging	0.87
R8818:Top3a	UTSW	11	60743051	missense	probably damaging	1.00
R8867:Top3a	UTSW	11	60742655	missense	probably benign	0.00
R8914:Top3a	UTSW	11	60740579	missense	probably damaging	1.00
R9031:Top3a	UTSW	11	60745869	missense	probably damaging	0.99
R9102:Top3a	UTSW	11	60756329	missense	probably damaging	1.00
R9103:Top3a	UTSW	11	60763427	critical splice acceptor site	probably null
R9130:Top3a	UTSW	11	60750575	critical splice donor site	probably null
R9548:Top3a	UTSW	11	60753942	missense	probably benign	0.19
R9578:Top3a	UTSW	11	60756691	missense	probably damaging	0.99
R9732:Top3a	UTSW	11	60749565	missense	probably benign	0.01
R9774:Top3a	UTSW	11	60748172	missense	probably damaging	0.98
X0063:Top3a	UTSW	11	60750644	nonsense	probably null
X0065:Top3a	UTSW	11	60763398	missense	probably damaging	1.00
Z1176:Top3a	UTSW	11	60742637	missense	probably benign	0.32
Z1177:Top3a	UTSW	11	60742816	missense	possibly damaging	0.56
Z1186:Top3a	UTSW	11	60750584	missense	probably benign
Z1187:Top3a	UTSW	11	60750584	missense	probably benign
Z1188:Top3a	UTSW	11	60750584	missense	probably benign
Z1189:Top3a	UTSW	11	60750584	missense	probably benign
Z1190:Top3a	UTSW	11	60750584	missense	probably benign
Z1191:Top3a	UTSW	11	60750584	missense	probably benign
Z1192:Top3a	UTSW	11	60750584	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- CCAGGTTGCACTGAAAAGAGTG -3'
(R):5'- AATGGTGGCTGTATCAACATGG -3'

Sequencing Primer
(F):5'- CACTGAAAAGAGTGAGTGTTGATTC -3'
(R):5'- GGTTTTGCCAAGTTACAATTAGTTCC -3'

Posted On

2016-08-04