Mutagenetix > Incidental Mutation

Incidental Mutation 'R4737:Lig3'

359361

Institutional Source

Beutler Lab

Gene Symbol

Lig3

Ensembl Gene

ENSMUSG00000020697

Gene Name

ligase III, DNA, ATP-dependent

Synonyms

D11Wsu78e

MMRRC Submission

042024-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4737 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

82781108-82804274 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 82787727 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 265 (L265P)

Ref Sequence

ENSEMBL: ENSMUSP00000133348 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021039] [ENSMUST00000080461] [ENSMUST00000092849] [ENSMUST00000131537] [ENSMUST00000173009] [ENSMUST00000173347] [ENSMUST00000173722] [ENSMUST00000173727]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000021039
AA Change: L265P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000021039
Gene: ENSMUSG00000020697
AA Change: L265P

Domain	Start	End	E-Value	Type
zf-PARP	97	183	8.89e-32	SMART
low complexity region	188	202	N/A	INTRINSIC
Pfam:DNA_ligase_A_N	265	440	3.5e-34	PFAM
Pfam:DNA_ligase_A_M	489	683	3.9e-65	PFAM
Pfam:DNA_ligase_A_C	710	820	3.8e-21	PFAM
low complexity region	855	885	N/A	INTRINSIC
BRCT	942	1010	9.77e-8	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000080461
AA Change: L265P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000079317
Gene: ENSMUSG00000020697
AA Change: L265P

Domain	Start	End	E-Value	Type
zf-PARP	97	183	8.89e-32	SMART
low complexity region	188	202	N/A	INTRINSIC
Pfam:DNA_ligase_A_N	263	437	6.8e-53	PFAM
Pfam:DNA_ligase_A_M	485	679	1.3e-63	PFAM
Pfam:DNA_ligase_A_C	706	816	3.2e-21	PFAM
low complexity region	851	881	N/A	INTRINSIC
low complexity region	934	946	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000092849
AA Change: L265P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000090525
Gene: ENSMUSG00000020697
AA Change: L265P

Domain	Start	End	E-Value	Type
zf-PARP	97	183	8.89e-32	SMART
low complexity region	188	202	N/A	INTRINSIC
Pfam:DNA_ligase_A_N	263	437	1.4e-52	PFAM
Pfam:DNA_ligase_A_M	485	679	7.2e-64	PFAM
Pfam:DNA_ligase_A_C	706	816	2.2e-21	PFAM
low complexity region	851	881	N/A	INTRINSIC
BRCT	938	1006	9.77e-8	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000131537
AA Change: L265P

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

SMART Domains

Protein: ENSMUSP00000133672
Gene: ENSMUSG00000020697
AA Change: L265P

Domain	Start	End	E-Value	Type
zf-PARP	97	183	8.89e-32	SMART
low complexity region	188	202	N/A	INTRINSIC
Pfam:DNA_ligase_A_N	263	431	3.1e-50	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000172609

Predicted Effect

probably damaging
Transcript: ENSMUST00000173009
AA Change: L265P

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

SMART Domains

Protein: ENSMUSP00000133348
Gene: ENSMUSG00000020697
AA Change: L265P

Domain	Start	End	E-Value	Type
zf-PARP	97	183	8.89e-32	SMART
low complexity region	188	202	N/A	INTRINSIC
Pfam:DNA_ligase_A_N	263	431	3.1e-50	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000173347
AA Change: L264P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000134300
Gene: ENSMUSG00000020697
AA Change: L264P

Domain	Start	End	E-Value	Type
zf-PARP	97	183	8.89e-32	SMART
low complexity region	188	202	N/A	INTRINSIC
Pfam:DNA_ligase_A_N	262	436	1.4e-52	PFAM
Pfam:DNA_ligase_A_M	484	678	7.2e-64	PFAM
Pfam:DNA_ligase_A_C	705	815	2.2e-21	PFAM
low complexity region	850	880	N/A	INTRINSIC
BRCT	937	1005	9.77e-8	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000173722
AA Change: L265P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000133805
Gene: ENSMUSG00000020697
AA Change: L265P

Domain	Start	End	E-Value	Type
zf-PARP	97	183	8.89e-32	SMART
low complexity region	188	202	N/A	INTRINSIC
Pfam:DNA_ligase_A_N	263	437	1.4e-52	PFAM
Pfam:DNA_ligase_A_M	485	679	7.2e-64	PFAM
Pfam:DNA_ligase_A_C	706	816	2.2e-21	PFAM
low complexity region	851	881	N/A	INTRINSIC
BRCT	938	1006	9.77e-8	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000173727
AA Change: L264P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000133849
Gene: ENSMUSG00000020697
AA Change: L264P

Domain	Start	End	E-Value	Type
zf-PARP	97	183	8.89e-32	SMART
low complexity region	188	202	N/A	INTRINSIC
Pfam:DNA_ligase_A_N	262	436	1.4e-52	PFAM
Pfam:DNA_ligase_A_M	484	678	7.2e-64	PFAM
Pfam:DNA_ligase_A_C	705	815	2.2e-21	PFAM
low complexity region	850	880	N/A	INTRINSIC
BRCT	937	1005	9.77e-8	SMART

Meta Mutation Damage Score

0.8257

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 95.3%

Validation Efficiency

100% (94/94)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the DNA ligase family. Each member of this family encodes a protein that catalyzes the joining of DNA ends but they each have a distinct role in DNA metabolism. The protein encoded by this gene is involved in excision repair and is located in both the mitochondria and nucleus, with translation initiation from the upstream start codon allowing for transport to the mitochondria and translation initiation from a downstream start codon allowing for transport to the nucleus. Additionally, alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
PHENOTYPE: Targeted inactivation of this gene causes embryonic growth arrest at 8.5 dpc, followed by excessive apoptosis at 9.5 dpc, and ultimately death, likely due to unrepaired DNA damage. Homozygous mutant cells display elevated sister chromatid exchange. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 88 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A430110L20Rik	A	G	1: 181,227,819		noncoding transcript	Het
Acp2	A	T	2: 91,210,723	R419W	probably benign	Het
Actr5	A	G	2: 158,628,071	N207S	probably damaging	Het
Afap1	G	A	5: 35,961,782	V254M	probably benign	Het
Arfgef1	A	T	1: 10,189,611	M544K	possibly damaging	Het
Arhgap5	A	T	12: 52,519,077	M944L	probably benign	Het
Bnip3l-ps	G	A	12: 18,216,772		noncoding transcript	Het
Carf	A	G	1: 60,109,318	T58A	probably benign	Het
Carns1	A	G	19: 4,170,928		probably benign	Het
Ccp110	T	A	7: 118,724,548	I670K	possibly damaging	Het
Cftr	T	A	6: 18,299,883	D1218E	probably benign	Het
Chrna9	A	T	5: 65,967,871	T52S	probably damaging	Het
Chst9	T	C	18: 15,452,777	Y243C	probably damaging	Het
Clk2	A	T	3: 89,168,709	H62L	probably benign	Het
Cntnap2	A	T	6: 45,060,317	R10W	possibly damaging	Het
Cpt1b	C	T	15: 89,421,406	D369N	probably benign	Het
Crhr2	G	T	6: 55,091,305	H423Q	probably damaging	Het
D8Ertd738e	T	A	8: 84,249,521	I33F	probably damaging	Het
Dbt	T	C	3: 116,539,132	I200T	probably damaging	Het
Ddhd1	A	T	14: 45,628,821		probably benign	Het
Ddx27	A	G	2: 167,029,299	I480V	probably benign	Het
Dpp9	A	C	17: 56,198,970		probably null	Het
Dpy19l3	A	T	7: 35,703,501	M562K	probably damaging	Het
Dus3l	T	C	17: 56,767,868	L330P	probably damaging	Het
Efcab7	C	T	4: 99,831,568	Q96*	probably null	Het
Egfr	T	C	11: 16,869,231	F254L	probably damaging	Het
Eml5	C	T	12: 98,798,852	V1566M	probably damaging	Het
Entpd7	T	A	19: 43,691,195	Y62*	probably null	Het
Erbb4	T	C	1: 68,343,900	M313V	probably damaging	Het
Gm5528	A	G	1: 72,004,552		noncoding transcript	Het
H2-M9	G	T	17: 36,640,739	Y281*	probably null	Het
Hmcn1	T	G	1: 150,689,595	K2260N	possibly damaging	Het
Hnf4a	A	G	2: 163,564,219	I259V	probably benign	Het
Ick	A	G	9: 78,150,654	T162A	probably damaging	Het
Insm1	A	T	2: 146,222,902	T213S	probably benign	Het
Iqca	T	C	1: 90,077,822	D488G	probably damaging	Het
Kdm5a	T	A	6: 120,406,015		probably benign	Het
Kdm7a	G	C	6: 39,152,839	L468V	possibly damaging	Het
Lck	G	A	4: 129,555,984	T229I	possibly damaging	Het
Lipa	T	A	19: 34,501,634	K229*	probably null	Het
Lrrk1	C	T	7: 66,306,873	S418N	probably benign	Het
Mark2	A	G	19: 7,281,232	V126A	probably damaging	Het
Met	T	C	6: 17,491,541	C101R	probably damaging	Het
Mkln1	A	T	6: 31,426,799	K85M	probably damaging	Het
Mst1	A	G	9: 108,080,521	R15G	probably benign	Het
Muc6	T	G	7: 141,640,159		probably benign	Het
Muc6	G	T	7: 141,638,772	T1996N	possibly damaging	Het
Myo7b	T	C	18: 31,998,602	S514G	probably damaging	Het
Narfl	A	T	17: 25,781,309	H322L	probably damaging	Het
Nars	T	C	18: 64,516,427	E11G	probably benign	Het
Ogdh	T	A	11: 6,297,044	F23I	probably benign	Het
Olfr1121	T	C	2: 87,372,321	I263T	probably damaging	Het
Olfr1186	C	T	2: 88,526,225	S214F	probably damaging	Het
Olfr1238	C	T	2: 89,406,486	V198I	probably benign	Het
Olfr1272	A	G	2: 90,282,381	S65P	probably damaging	Het
Olfr584	C	T	7: 103,085,914	A127V	probably damaging	Het
Olfr825	T	A	10: 130,162,838	T163S	probably benign	Het
Olfr979	A	T	9: 40,000,422	D268E	probably damaging	Het
Otub2	T	A	12: 103,392,844	L64Q	probably benign	Het
Pappa2	T	C	1: 158,957,012	R143G	probably benign	Het
Patl2	T	A	2: 122,125,306	T250S	probably damaging	Het
Pcdhac2	C	T	18: 37,145,899	T644I	possibly damaging	Het
Pi4kb	C	T	3: 95,004,338	T690I	probably damaging	Het
Pla2g4d	T	C	2: 120,266,790	Y776C	probably benign	Het
Plekhh2	C	T	17: 84,563,959	S215L	probably benign	Het
Psmd2	T	G	16: 20,659,815		probably benign	Het
Ptpn21	T	C	12: 98,708,844	E183G	probably benign	Het
Ptprg	T	A	14: 12,226,314	D527E	probably damaging	Het
Rhobtb1	T	A	10: 69,279,497		probably null	Het
Scel	T	A	14: 103,572,037	M271K	possibly damaging	Het
Senp3	A	T	11: 69,678,829	C310*	probably null	Het
Slc25a3	T	C	10: 91,122,188	T97A	possibly damaging	Het
Srsf11	A	T	3: 158,026,732	Y82*	probably null	Het
Tbc1d8	G	A	1: 39,402,878	T211I	possibly damaging	Het
Tbkbp1	T	C	11: 97,148,648	E145G	probably damaging	Het
Tln1	T	C	4: 43,540,588	N1471S	probably benign	Het
Tnn	T	G	1: 160,146,089	D236A	probably damaging	Het
Trmt2a	C	T	16: 18,251,286		probably benign	Het
Ttn	A	T	2: 76,811,243	L5176Q	possibly damaging	Het
Ubxn10	G	A	4: 138,735,948		probably benign	Het
Ulk4	G	A	9: 121,073,872	Q1180*	probably null	Het
Usp43	T	A	11: 67,855,505	K1120N	probably damaging	Het
Uspl1	T	A	5: 149,194,339	L244Q	possibly damaging	Het
Vmn1r32	T	C	6: 66,553,645	H49R	probably damaging	Het
Vmn2r4	T	C	3: 64,409,963	D118G	probably damaging	Het
Vwce	A	G	19: 10,650,579	I468V	probably benign	Het
Zbtb7c	G	T	18: 76,146,154	R561L	probably benign	Het
Zfp956	T	C	6: 47,962,542	S175P	probably damaging	Het

Other mutations in Lig3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01066:Lig3	APN	11	82797315	missense	possibly damaging	0.90
IGL01577:Lig3	APN	11	82783477	missense	probably benign	0.00
IGL01643:Lig3	APN	11	82798292	missense	probably damaging	1.00
IGL01712:Lig3	APN	11	82789541	splice site	probably benign
IGL01724:Lig3	APN	11	82790622	missense	possibly damaging	0.95
IGL01749:Lig3	APN	11	82789867	missense	probably damaging	1.00
IGL01778:Lig3	APN	11	82794541	missense	probably damaging	1.00
IGL02798:Lig3	APN	11	82795705	splice site	probably benign
IGL03007:Lig3	APN	11	82789575	missense	probably damaging	1.00
IGL03178:Lig3	APN	11	82789722	splice site	probably benign
R0001:Lig3	UTSW	11	82790591	missense	probably damaging	1.00
R0115:Lig3	UTSW	11	82793935	missense	probably damaging	1.00
R0834:Lig3	UTSW	11	82798287	missense	probably damaging	0.99
R1460:Lig3	UTSW	11	82795798	splice site	probably benign
R1602:Lig3	UTSW	11	82792194	critical splice donor site	probably null
R1969:Lig3	UTSW	11	82795718	missense	probably benign	0.14
R1971:Lig3	UTSW	11	82795718	missense	probably benign	0.14
R1997:Lig3	UTSW	11	82787666	missense	probably benign	0.00
R3817:Lig3	UTSW	11	82796115	missense	possibly damaging	0.75
R4083:Lig3	UTSW	11	82790494	missense	probably benign	0.31
R4084:Lig3	UTSW	11	82795424	missense	probably damaging	1.00
R4665:Lig3	UTSW	11	82800250	missense	probably damaging	0.99
R5212:Lig3	UTSW	11	82787678	missense	probably benign
R5274:Lig3	UTSW	11	82797292	splice site	probably null
R6320:Lig3	UTSW	11	82794007	critical splice donor site	probably null
R6807:Lig3	UTSW	11	82783751	missense	probably benign	0.00
R7103:Lig3	UTSW	11	82797312	missense	probably benign	0.17
R7552:Lig3	UTSW	11	82788891	missense	probably benign	0.00
R7646:Lig3	UTSW	11	82783478	missense	probably benign	0.00
R7910:Lig3	UTSW	11	82797775	missense	probably damaging	0.99
R7966:Lig3	UTSW	11	82790516	missense	probably damaging	1.00
R8001:Lig3	UTSW	11	82792076	missense	probably benign	0.18
R8436:Lig3	UTSW	11	82792044	missense	possibly damaging	0.82
R8699:Lig3	UTSW	11	82794550	missense	probably damaging	1.00
R9352:Lig3	UTSW	11	82796145	missense	probably benign	0.01
R9392:Lig3	UTSW	11	82789840	missense	probably benign	0.06
R9452:Lig3	UTSW	11	82790622	missense	probably damaging	1.00
R9469:Lig3	UTSW	11	82795373	missense	probably benign	0.01
R9726:Lig3	UTSW	11	82783594	missense	possibly damaging	0.89

Predicted Primers

PCR Primer
(F):5'- GGGGCTTGCATAAAATGGC -3'
(R):5'- AATTCCGATATACAAGTGTCTGCAC -3'

Sequencing Primer
(F):5'- GCTTGCATAAAATGGCATAAGC -3'
(R):5'- TGTCTGCACATCAAGCTGG -3'

Posted On

2015-11-11