Mutagenetix > Incidental Mutations

Incidental Mutation 'R5419:Top3a'

427941

Institutional Source

Beutler Lab

Gene Symbol

Top3a

Ensembl Gene

ENSMUSG00000002814

Gene Name

topoisomerase (DNA) III alpha

Synonyms

Top IIIa

MMRRC Submission

042987-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R5419 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

60740058-60777365 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 60762522 bp

Zygosity

Heterozygous

Amino Acid Change

Threonine to Isoleucine at position 42 (T42I)

Ref Sequence

ENSEMBL: ENSMUSP00000115727 (fasta)

Gene Model

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000002891
AA Change: T87I

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

SMART Domains

Protein: ENSMUSP00000002891
Gene: ENSMUSG00000002814
AA Change: T87I

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: T87I

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

SMART Domains

Protein: ENSMUSP00000099729
Gene: ENSMUSG00000002814
AA Change: T87I

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: T62I

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

SMART Domains

Protein: ENSMUSP00000113057
Gene: ENSMUSG00000002814
AA Change: T62I

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: T62I

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

SMART Domains

Protein: ENSMUSP00000113653
Gene: ENSMUSG00000002814
AA Change: T62I

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: T42I

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

SMART Domains

Protein: ENSMUSP00000115727
Gene: ENSMUSG00000002814
AA Change: T42I

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

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.4%

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 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: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2610507B11Rik	T	A	11: 78,272,090	L926*	probably null	Het
4931429L15Rik	C	T	9: 46,309,326		probably null	Het
Abca13	T	A	11: 9,193,533		probably null	Het
AI481877	A	T	4: 59,049,017	M1116K	probably benign	Het
Akap13	A	T	7: 75,610,243	T69S	probably benign	Het
Arl1	T	A	10: 88,737,104	C80S	probably damaging	Het
Brsk1	A	G	7: 4,709,004	T618A	possibly damaging	Het
Cep295	T	C	9: 15,324,237	H1982R	probably damaging	Het
Ces5a	A	T	8: 93,499,431	S559T	unknown	Het
Clcf1	A	G	19: 4,222,159	N90S	possibly damaging	Het
Clec16a	G	A	16: 10,731,679	C872Y	probably damaging	Het
Cobll1	A	T	2: 65,103,357	D430E	possibly damaging	Het
Cyp1a2	T	A	9: 57,682,511	I7F	probably benign	Het
Cyp2b23	G	A	7: 26,681,423	R126*	probably null	Het
Daam2	A	G	17: 49,480,754	W444R	possibly damaging	Het
Dcbld2	T	A	16: 58,455,258	C446S	probably damaging	Het
Dnase1l1	C	T	X: 74,277,038		probably null	Het
Eif2d	T	C	1: 131,158,298	*177R	probably null	Het
Fkbp15	G	A	4: 62,327,877	A438V	probably damaging	Het
Gjb5	G	A	4: 127,355,859	A164V	probably benign	Het
Gm17727	T	A	9: 35,778,111		probably null	Het
Gm5724	C	T	6: 141,736,100		probably null	Het
Grin1	A	T	2: 25,298,273		probably null	Het
Grm3	A	G	5: 9,570,233	F337S	probably damaging	Het
Hey2	T	A	10: 30,834,023	T245S	probably benign	Het
Ifi206	T	C	1: 173,481,231	T400A	probably benign	Het
Itga7	G	A	10: 128,944,033	E480K	probably null	Het
Itpr1	T	C	6: 108,493,794	Y2227H	possibly damaging	Het
Krt8	T	C	15: 102,003,902	D113G	probably damaging	Het
Lgr6	C	T	1: 134,994,010	A199T	probably damaging	Het
Lins1	A	G	7: 66,708,095		probably benign	Het
Lmf1	A	T	17: 25,662,636	D553V	possibly damaging	Het
Lnpep	A	G	17: 17,566,730	S536P	probably damaging	Het
Lrp1b	A	T	2: 40,730,704	C3587*	probably null	Het
Macf1	A	T	4: 123,397,124	D3435E	possibly damaging	Het
Mmp1b	T	C	9: 7,384,897	I251V	possibly damaging	Het
Myg1	A	T	15: 102,336,962	N206I	probably damaging	Het
Myl12a	T	G	17: 70,994,699	R144S	probably benign	Het
Myo5a	T	A	9: 75,147,897	I454K	probably damaging	Het
Nwd2	A	G	5: 63,807,708	D1545G	probably benign	Het
Ogdhl	T	G	14: 32,339,224	D457E	probably damaging	Het
Olfr202	T	A	16: 59,284,341	D52V	probably damaging	Het
Olfr466	A	C	13: 65,152,774	L183F	probably damaging	Het
Paf1	A	G	7: 28,395,670	I112V	possibly damaging	Het
Pcdhga4	C	T	18: 37,686,745	P449L	probably damaging	Het
Pla2g6	A	T	15: 79,299,142	I495N	possibly damaging	Het
Ptgs1	A	G	2: 36,237,222	Y40C	probably damaging	Het
Ptprn2	A	T	12: 117,184,647	I676F	probably damaging	Het
Rev3l	T	C	10: 39,824,931	L1808P	possibly damaging	Het
Sall2	A	G	14: 52,313,129	S868P	probably damaging	Het
Slc47a2	A	G	11: 61,307,586	F428L	probably benign	Het
Slco3a1	A	T	7: 74,284,615	F603Y	possibly damaging	Het
Smyd2	A	T	1: 189,909,893	C65*	probably null	Het
Ssu72	T	C	4: 155,715,550	F57L	probably damaging	Het
Tanc2	A	G	11: 105,922,883	T1718A	probably benign	Het
Tnks	G	C	8: 34,965,566	P34A	unknown	Het
Trank1	T	C	9: 111,391,301	S2369P	probably damaging	Het
Ttn	A	T	2: 76,811,243	L5176Q	possibly damaging	Het
Ubqln1	T	C	13: 58,183,183	Q410R	probably damaging	Het
Vmn2r11	A	G	5: 109,059,358	I32T	possibly damaging	Het
Xcr1	A	G	9: 123,856,310	F129S	probably benign	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
R5387:Top3a	UTSW	11	60762490	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
X0063:Top3a	UTSW	11	60750644	nonsense	probably null
X0065:Top3a	UTSW	11	60763398	missense	probably damaging	1.00

Predicted Primers

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

Sequencing Primer
(F):5'- CTTACAGCAGGTCATATAGCCTTAGG -3'
(R):5'- ATCAACATGGTTTTGGTTTTGCC -3'

Posted On

2016-09-01