Mutagenetix > Incidental Mutation

Incidental Mutation 'R1839:Top3a'

205619

Institutional Source

Beutler Lab

Gene Symbol

Top3a

Ensembl Gene

ENSMUSG00000002814

Gene Name

topoisomerase (DNA) III alpha

Synonyms

Top IIIa

MMRRC Submission

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R1839 (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 60753888 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 305 (V305A)

Ref Sequence

ENSEMBL: ENSMUSP00000113057 (fasta)

Gene Model

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

AlphaFold

O70157

Predicted Effect

probably damaging
Transcript: ENSMUST00000002891
AA Change: V330A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000002891
Gene: ENSMUSG00000002814
AA Change: V330A

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: V330A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000099729
Gene: ENSMUSG00000002814
AA Change: V330A

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: V305A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000113057
Gene: ENSMUSG00000002814
AA Change: V305A

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: V305A

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000113653
Gene: ENSMUSG00000002814
AA Change: V305A

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

noncoding transcript
Transcript: ENSMUST00000124799

Meta Mutation Damage Score

0.8455

Coding Region Coverage

1x: 97.4%
3x: 96.7%
10x: 94.7%
20x: 90.6%

Validation Efficiency

98% (90/92)

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: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700006A11Rik	T	C	3: 124,409,720	T403A	probably damaging	Het
Acat3	T	A	17: 12,928,606	R175*	probably null	Het
Adam1b	C	A	5: 121,501,041	C647F	probably damaging	Het
Adam28	T	C	14: 68,639,210	N197S	possibly damaging	Het
Adcy2	C	T	13: 68,689,261		probably null	Het
Adcy5	A	T	16: 35,248,940	N426I	probably damaging	Het
Adgre1	T	C	17: 57,441,299	S500P	probably benign	Het
Aloxe3	A	G	11: 69,130,085	Y212C	probably damaging	Het
Ap3d1	A	G	10: 80,727,108	S180P	probably damaging	Het
Arhgap20	C	T	9: 51,849,326	R790W	probably damaging	Het
Atp8b4	C	A	2: 126,361,782	A757S	possibly damaging	Het
Begain	G	A	12: 109,035,323		probably benign	Het
Ccdc141	T	C	2: 77,011,665	E1474G	probably benign	Het
Ccdc88b	A	G	19: 6,854,109		probably benign	Het
Ccnk	A	G	12: 108,195,074	T195A	probably damaging	Het
Cd55b	C	A	1: 130,414,105	C265F	probably damaging	Het
Celsr3	A	G	9: 108,829,906	H1196R	probably benign	Het
Cenpt	T	C	8: 105,849,014	S190G	possibly damaging	Het
Chd8	T	C	14: 52,204,883	S2077G	probably benign	Het
Col6a5	G	A	9: 105,864,833	H2296Y	probably benign	Het
Cxxc4	C	A	3: 134,240,653	H332N	probably damaging	Het
Cyp24a1	T	C	2: 170,496,741	I12V	probably benign	Het
Cyp3a57	T	A	5: 145,381,301	L364Q	probably damaging	Het
Ddi2	T	C	4: 141,713,526	I47V	probably benign	Het
Ddx5	A	T	11: 106,784,897	D322E	probably benign	Het
Dhx40	A	G	11: 86,789,297	C405R	possibly damaging	Het
Emc1	T	C	4: 139,360,485	F100S	probably damaging	Het
Exoc2	T	C	13: 30,906,497		probably benign	Het
Gm10110	A	T	14: 89,897,836		noncoding transcript	Het
Gm17332	T	C	11: 31,182,386	H26R	possibly damaging	Het
Gna12	T	C	5: 140,762,612	N183S	probably benign	Het
Gpx6	A	G	13: 21,312,327	N24D	probably benign	Het
Gsdma3	C	T	11: 98,629,858	A105V	probably benign	Het
Hsd3b5	T	C	3: 98,619,728	Y134C	probably benign	Het
Ifi213	T	C	1: 173,589,600	I415M	probably damaging	Het
Ints9	C	A	14: 65,016,530	P278T	probably damaging	Het
Krt79	C	T	15: 101,937,938	E192K	possibly damaging	Het
Lrrk2	A	G	15: 91,683,134	N132S	probably benign	Het
Ltn1	T	A	16: 87,416,264	K470*	probably null	Het
Magi2	A	T	5: 20,465,827	T163S	probably damaging	Het
Mcm9	A	G	10: 53,541,553	M18T	probably damaging	Het
Med12l	A	G	3: 59,068,319	T212A	probably benign	Het
Mfhas1	T	C	8: 35,590,858	L829P	possibly damaging	Het
Mgme1	T	A	2: 144,279,487	C288S	probably benign	Het
Muc4	G	C	16: 32,753,919	R1265P	probably benign	Het
Myh7	T	C	14: 54,973,180	N1725S	possibly damaging	Het
Nat6	G	A	9: 107,583,017	R37H	possibly damaging	Het
Nme4	A	T	17: 26,092,097	W165R	probably damaging	Het
Nup205	T	A	6: 35,219,714	D1128E	probably benign	Het
Olfr291	T	C	7: 84,856,548	Y60H	probably damaging	Het
Olfr330	A	T	11: 58,529,373	Y204*	probably null	Het
Pcdh1	T	C	18: 38,199,485	D155G	possibly damaging	Het
Pex12	A	T	11: 83,297,822	S116T	probably damaging	Het
Plekhh1	C	T	12: 79,078,957		probably benign	Het
Plekhh3	A	G	11: 101,163,600		probably benign	Het
Pnpt1	T	C	11: 29,154,342	M572T	possibly damaging	Het
Ppp1r12b	T	C	1: 134,837,981	R667G	probably benign	Het
Rbpms2	ACTGCTGCTGCTGCTGC	ACTGCTGCTGCTGCTGCTGC	9: 65,651,666		probably benign	Het
Rgs14	T	C	13: 55,382,838		probably benign	Het
Rhbdf2	A	T	11: 116,600,191	V645E	possibly damaging	Het
Robo3	A	G	9: 37,422,327	V696A	probably benign	Het
Sall1	A	G	8: 89,028,716	F1212L	possibly damaging	Het
Sdc4	T	C	2: 164,429,012	E109G	probably benign	Het
Serpind1	G	T	16: 17,342,992	R462L	probably damaging	Het
Smad9	CTTT	CTT	3: 54,789,179		probably benign	Het
Sstr4	C	A	2: 148,395,533	N21K	probably benign	Het
Tap1	C	T	17: 34,188,109	A77V	possibly damaging	Het
Thap4	T	C	1: 93,750,287	E259G	probably benign	Het
Thra	A	G	11: 98,756,143	N30S	probably benign	Het
Tmem207	A	T	16: 26,524,821	V27E	possibly damaging	Het
Trim59	A	T	3: 69,037,638	I123K	probably damaging	Het
Ttn	T	C	2: 76,861,495		probably benign	Het
Ubac1	T	A	2: 26,007,738	E290V	possibly damaging	Het
Unc13b	T	C	4: 43,258,308		probably benign	Het
Uri1	A	T	7: 37,967,389	D206E	probably benign	Het
Utp4	A	G	8: 106,913,454	H465R	probably benign	Het
Uvssa	T	C	5: 33,389,752	S221P	probably benign	Het
Vmn1r39	T	C	6: 66,805,233		probably null	Het
Vps39	A	T	2: 120,325,397	L514H	probably damaging	Het
Vps72	G	A	3: 95,119,218	R158Q	possibly damaging	Het
Wdr59	T	C	8: 111,485,340	D366G	probably benign	Het
Zfp366	C	A	13: 99,228,492	Q54K	probably damaging	Het
Zfp523	T	A	17: 28,194,993	I34N	probably damaging	Het
Zfp974	G	A	7: 27,910,356	P648L	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
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
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'- TTAAGAGGCTGGGATAACGC -3'
(R):5'- GCACAGAATGAGTGATGTTGC -3'

Sequencing Primer
(F):5'- GAATTTGCTCTGTCGACCAGGC -3'
(R):5'- CACAGAATGAGTGATGTTGCATGGG -3'

Posted On

2014-06-23