Mutagenetix > Incidental Mutation

Incidental Mutation 'R5153:Lig4'

395520

Institutional Source

Beutler Lab

Gene Symbol

Lig4

Ensembl Gene

ENSMUSG00000049717

Gene Name

ligase IV, DNA, ATP-dependent

Synonyms

DNA ligase IV, tiny, 5830471N16Rik

MMRRC Submission

042735-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5153 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

10020020-10027680 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 10023003 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Glutamic Acid at position 259 (V259E)

Ref Sequence

ENSEMBL: ENSMUSP00000130807 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000048216] [ENSMUST00000095476] [ENSMUST00000139793] [ENSMUST00000170033]

AlphaFold

Q8BTF7

Predicted Effect

probably benign
Transcript: ENSMUST00000048216

SMART Domains

Protein: ENSMUSP00000036730
Gene: ENSMUSG00000040396

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
transmembrane domain	39	58	N/A	INTRINSIC
Pfam:Abhydrolase_5	116	299	5.6e-24	PFAM
Pfam:Abhydrolase_3	117	279	1.7e-6	PFAM
Pfam:Abhydrolase_6	117	310	4.9e-15	PFAM
Pfam:Abhydrolase_1	143	245	1.8e-8	PFAM
Pfam:AXE1	163	229	3.7e-8	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000095476
AA Change: V259E

PolyPhen 2 Score 0.951 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: V259E

Domain	Start	End	E-Value	Type
Pfam:DNA_ligase_A_N	14	209	1.3e-43	PFAM
Pfam:DNA_ligase_A_M	248	451	2e-50	PFAM
Pfam:DNA_ligase_A_C	476	588	3.3e-16	PFAM
BRCT	656	733	2.8e-14	SMART
Pfam:DNA_ligase_IV	749	784	7.3e-21	PFAM
BRCT	816	901	1.6e-5	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000139793

SMART Domains

Protein: ENSMUSP00000116130
Gene: ENSMUSG00000040396

Domain	Start	End	E-Value	Type
transmembrane domain	15	37	N/A	INTRINSIC
transmembrane domain	39	58	N/A	INTRINSIC
Pfam:Hydrolase_4	111	250	2.5e-11	PFAM
Pfam:Abhydrolase_1	115	237	3.2e-11	PFAM
Pfam:Abhydrolase_5	116	299	6.3e-24	PFAM
Pfam:Abhydrolase_6	117	241	2.9e-8	PFAM
Pfam:AXE1	162	229	9.1e-8	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000170033
AA Change: V259E

PolyPhen 2 Score 0.951 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: V259E

Domain	Start	End	E-Value	Type
Pfam:DNA_ligase_A_N	15	208	8.8e-39	PFAM
Pfam:DNA_ligase_A_M	248	451	2.3e-52	PFAM
Pfam:DNA_ligase_A_C	476	588	4.8e-18	PFAM
BRCT	656	733	2.9e-14	SMART
Pfam:DNA_ligase_IV	750	783	5.5e-17	PFAM
BRCT	816	901	1.6e-5	SMART

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.2%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
PHENOTYPE: Null homozygotes die late in gestation with extensive CNS apoptosis, blocked lymphopoeiesis and failure of V(D)J joining. Carrier fibroblasts show elevated chromosome breaks. ~40% of homozygous hypomorphs survive, with retarded growth, reduced PBL and progressive loss of hematopoietic stem cells. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2300003K06Rik	A	T	11: 99,728,073 (GRCm39)	C257S	unknown	Het
4930596D02Rik	C	A	14: 35,532,212 (GRCm39)	R121L	probably benign	Het
Aadacl4fm1	T	A	4: 144,248,837 (GRCm39)	M68K	probably benign	Het
Acin1	A	G	14: 54,883,070 (GRCm39)	V194A	probably benign	Het
Acsm1	T	C	7: 119,239,950 (GRCm39)	I298T	possibly damaging	Het
Aoc1	A	G	6: 48,885,681 (GRCm39)	N729D	probably benign	Het
Apobr	C	T	7: 126,186,904 (GRCm39)	T20I	possibly damaging	Het
Arsb	A	G	13: 94,077,106 (GRCm39)	E491G	probably benign	Het
AW209491	C	G	13: 14,811,764 (GRCm39)	Q206E	probably benign	Het
Camsap1	A	T	2: 25,823,630 (GRCm39)	N1473K	probably damaging	Het
Casp8	A	G	1: 58,884,004 (GRCm39)	Q457R	probably benign	Het
Ccdc154	G	A	17: 25,387,315 (GRCm39)	A350T	probably damaging	Het
Cecr2	A	G	6: 120,711,521 (GRCm39)	E183G	probably benign	Het
Cep295	A	T	9: 15,268,925 (GRCm39)	S39T	probably benign	Het
Cep350	A	T	1: 155,811,692 (GRCm39)	I416K	probably damaging	Het
Cidea	C	T	18: 67,500,490 (GRCm39)	T184M	probably damaging	Het
Cnot10	G	A	9: 114,442,803 (GRCm39)	A468V	probably damaging	Het
Cstdc1	A	G	2: 148,625,360 (GRCm39)	Q98R	probably benign	Het
Defb22	A	T	2: 152,327,722 (GRCm39)	N154K	unknown	Het
Dnah17	A	T	11: 117,973,800 (GRCm39)	C1915*	probably null	Het
Dnah2	T	C	11: 69,411,759 (GRCm39)	T288A	possibly damaging	Het
Dop1b	T	A	16: 93,570,891 (GRCm39)	M1512K	probably damaging	Het
Dsp	T	G	13: 38,366,282 (GRCm39)	I572S	probably damaging	Het
Eepd1	A	G	9: 25,498,049 (GRCm39)	H378R	probably benign	Het
Elapor1	A	T	3: 108,380,063 (GRCm39)	Y349N	possibly damaging	Het
Emilin2	A	G	17: 71,580,497 (GRCm39)	M743T	possibly damaging	Het
Ext1	C	A	15: 52,939,213 (GRCm39)	W612L	probably damaging	Het
F2rl2	A	G	13: 95,833,620 (GRCm39)	T17A	probably benign	Het
Fbxl8	T	G	8: 105,993,739 (GRCm39)	C32G	probably damaging	Het
Fbxw17	A	G	13: 50,573,897 (GRCm39)	T38A	probably damaging	Het
Flii	A	T	11: 60,607,512 (GRCm39)	L882Q	possibly damaging	Het
Focad	T	G	4: 88,278,121 (GRCm39)	S1197A	unknown	Het
H1f11-ps	A	G	19: 47,159,356 (GRCm39)	V73A	probably damaging	Het
Heatr5b	G	A	17: 79,102,536 (GRCm39)	R1281*	probably null	Het
Khdc3	A	G	9: 73,010,720 (GRCm39)	Q190R	probably benign	Het
Krt9	T	A	11: 100,082,068 (GRCm39)	D244V	probably damaging	Het
Ldhd	T	C	8: 112,353,724 (GRCm39)	E463G	probably benign	Het
Luc7l3	A	T	11: 94,186,806 (GRCm39)		probably benign	Het
Man1a2	T	C	3: 100,563,579 (GRCm39)	E22G	probably damaging	Het
Mmp23	T	G	4: 155,735,797 (GRCm39)	D258A	probably damaging	Het
Msantd2	C	T	9: 37,434,509 (GRCm39)	R250*	probably null	Het
Mynn	T	C	3: 30,665,738 (GRCm39)	S457P	probably benign	Het
Nectin1	C	T	9: 43,714,795 (GRCm39)	H50Y	probably damaging	Het
Or10a3b	T	C	7: 108,444,906 (GRCm39)	I104V	probably benign	Het
Or2d3c	C	T	7: 106,525,776 (GRCm39)	V297M	possibly damaging	Het
Or4a47	G	A	2: 89,665,578 (GRCm39)	T237I	possibly damaging	Het
Or6c6c	A	G	10: 129,541,026 (GRCm39)	N93S	probably benign	Het
Pfkfb2	G	A	1: 130,629,527 (GRCm39)	T303M	probably damaging	Het
Pkhd1l1	A	G	15: 44,368,705 (GRCm39)	D841G	probably benign	Het
Plxna4	A	T	6: 32,201,094 (GRCm39)		probably null	Het
Podnl1	C	T	8: 84,857,272 (GRCm39)	H294Y	probably benign	Het
Ppig	T	A	2: 69,579,994 (GRCm39)	D509E	unknown	Het
Ppp1r16a	T	A	15: 76,578,596 (GRCm39)	Y433*	probably null	Het
Prdm1	A	C	10: 44,326,221 (GRCm39)	V134G	possibly damaging	Het
Prx	T	C	7: 27,217,901 (GRCm39)	S940P	probably damaging	Het
Ptprd	C	T	4: 75,930,339 (GRCm39)	V731I	probably damaging	Het
Qki	A	G	17: 10,457,820 (GRCm39)		probably null	Het
Rassf6	T	C	5: 90,754,699 (GRCm39)	K206R	possibly damaging	Het
Rdh16f2	G	A	10: 127,712,124 (GRCm39)	E194K	possibly damaging	Het
Rims1	C	A	1: 22,522,328 (GRCm39)	G457*	probably null	Het
Ripk1	T	G	13: 34,197,279 (GRCm39)	I123R	probably damaging	Het
Rnf111	A	T	9: 70,383,422 (GRCm39)	S170R	probably benign	Het
Shc3	A	T	13: 51,615,413 (GRCm39)	F181L	probably damaging	Het
Siglec1	A	C	2: 130,927,497 (GRCm39)	V103G	probably damaging	Het
Slc26a11	G	T	11: 119,268,085 (GRCm39)	A488S	possibly damaging	Het
Smoc2	A	T	17: 14,556,841 (GRCm39)	T97S	probably damaging	Het
Son	T	C	16: 91,451,910 (GRCm39)	I219T	possibly damaging	Het
Sptbn1	A	T	11: 30,071,510 (GRCm39)	I1474N	possibly damaging	Het
Syt16	A	T	12: 74,269,542 (GRCm39)	D127V	possibly damaging	Het
Tet1	G	T	10: 62,714,357 (GRCm39)	N479K	possibly damaging	Het
Thsd7a	G	A	6: 12,338,654 (GRCm39)	A1192V	probably benign	Het
Tmed3	G	A	9: 89,581,825 (GRCm39)	R213*	probably null	Het
Traj57	A	G	14: 54,396,016 (GRCm39)		probably benign	Het
Trpv1	G	T	11: 73,129,342 (GRCm39)	R86S	probably benign	Het
Usp48	T	A	4: 137,343,673 (GRCm39)	F434L	possibly damaging	Het
Vmn2r59	A	C	7: 41,691,834 (GRCm39)		probably null	Het
Vmn2r71	T	A	7: 85,268,430 (GRCm39)	I211N	possibly damaging	Het
Vps13b	T	A	15: 35,422,599 (GRCm39)	D186E	probably damaging	Het
Vps33a	A	G	5: 123,696,691 (GRCm39)	S321P	probably damaging	Het
Wdr12	A	T	1: 60,133,670 (GRCm39)	D19E	probably benign	Het
Zc3h12c	A	G	9: 52,037,947 (GRCm39)	F278L	probably damaging	Het
Zpld1	T	C	16: 55,067,007 (GRCm39)	T183A	probably damaging	Het
Zswim2	G	T	2: 83,770,010 (GRCm39)	T68K	possibly damaging	Het

Other mutations in Lig4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00229:Lig4	APN	8	10,022,775 (GRCm39)	missense	probably damaging	1.00
IGL00655:Lig4	APN	8	10,023,305 (GRCm39)	missense	probably benign	0.09
IGL01388:Lig4	APN	8	10,023,586 (GRCm39)	missense	probably damaging	1.00
IGL01669:Lig4	APN	8	10,023,673 (GRCm39)	missense	probably benign	0.01
IGL01757:Lig4	APN	8	10,021,185 (GRCm39)	missense	probably benign	0.10
IGL02115:Lig4	APN	8	10,023,247 (GRCm39)	missense	possibly damaging	0.58
IGL02167:Lig4	APN	8	10,021,821 (GRCm39)	missense	probably benign	0.06
IGL02239:Lig4	APN	8	10,022,473 (GRCm39)	missense	probably damaging	1.00
IGL02576:Lig4	APN	8	10,021,116 (GRCm39)	missense	probably damaging	1.00
IGL02955:Lig4	APN	8	10,022,103 (GRCm39)	missense	possibly damaging	0.95
IGL03056:Lig4	APN	8	10,022,580 (GRCm39)	missense	possibly damaging	0.90
nosegay	UTSW	8	10,022,954 (GRCm39)	missense	probably damaging	1.00
posey	UTSW	8	10,022,955 (GRCm39)	missense	probably damaging	1.00
posey2	UTSW	8	10,021,585 (GRCm39)	missense	probably benign
BB004:Lig4	UTSW	8	10,023,629 (GRCm39)	missense	possibly damaging	0.92
BB014:Lig4	UTSW	8	10,023,629 (GRCm39)	missense	possibly damaging	0.92
R0791:Lig4	UTSW	8	10,023,012 (GRCm39)	missense	possibly damaging	0.70
R1208:Lig4	UTSW	8	10,021,062 (GRCm39)	missense	probably damaging	1.00
R1208:Lig4	UTSW	8	10,021,062 (GRCm39)	missense	probably damaging	1.00
R1368:Lig4	UTSW	8	10,021,176 (GRCm39)	missense	possibly damaging	0.89
R1522:Lig4	UTSW	8	10,023,012 (GRCm39)	missense	possibly damaging	0.70
R1566:Lig4	UTSW	8	10,023,650 (GRCm39)	missense	probably benign	0.41
R1674:Lig4	UTSW	8	10,021,692 (GRCm39)	missense	probably benign	0.01
R2024:Lig4	UTSW	8	10,022,436 (GRCm39)	missense	probably damaging	1.00
R2025:Lig4	UTSW	8	10,022,436 (GRCm39)	missense	probably damaging	1.00
R2026:Lig4	UTSW	8	10,022,436 (GRCm39)	missense	probably damaging	1.00
R2155:Lig4	UTSW	8	10,022,766 (GRCm39)	missense	probably benign	0.00
R2243:Lig4	UTSW	8	10,022,161 (GRCm39)	missense	possibly damaging	0.81
R2917:Lig4	UTSW	8	10,021,596 (GRCm39)	missense	possibly damaging	0.56
R4763:Lig4	UTSW	8	10,022,955 (GRCm39)	missense	probably damaging	1.00
R4819:Lig4	UTSW	8	10,021,885 (GRCm39)	missense	probably benign
R5397:Lig4	UTSW	8	10,022,644 (GRCm39)	missense	probably benign	0.01
R5618:Lig4	UTSW	8	10,022,021 (GRCm39)	missense	probably benign
R6102:Lig4	UTSW	8	10,022,872 (GRCm39)	missense	probably damaging	1.00
R6210:Lig4	UTSW	8	10,021,585 (GRCm39)	missense	probably benign
R6312:Lig4	UTSW	8	10,021,739 (GRCm39)	missense	probably benign
R6955:Lig4	UTSW	8	10,023,384 (GRCm39)	missense	probably damaging	1.00
R6991:Lig4	UTSW	8	10,021,098 (GRCm39)	missense	probably damaging	0.99
R7207:Lig4	UTSW	8	10,022,101 (GRCm39)	nonsense	probably null
R7769:Lig4	UTSW	8	10,023,629 (GRCm39)	missense	possibly damaging	0.92
R7927:Lig4	UTSW	8	10,023,629 (GRCm39)	missense	possibly damaging	0.92
R8113:Lig4	UTSW	8	10,023,485 (GRCm39)	missense	probably benign	0.07
R8124:Lig4	UTSW	8	10,022,954 (GRCm39)	missense	probably damaging	1.00
R8382:Lig4	UTSW	8	10,022,346 (GRCm39)	missense	probably damaging	1.00
R8443:Lig4	UTSW	8	10,023,777 (GRCm39)	start codon destroyed	probably null	0.00
R8956:Lig4	UTSW	8	10,021,378 (GRCm39)	missense	probably benign
R9165:Lig4	UTSW	8	10,022,394 (GRCm39)	missense	probably damaging	1.00
R9170:Lig4	UTSW	8	10,022,202 (GRCm39)	missense	probably damaging	1.00
R9356:Lig4	UTSW	8	10,022,538 (GRCm39)	missense	possibly damaging	0.94
R9535:Lig4	UTSW	8	10,022,325 (GRCm39)	missense	probably damaging	1.00
R9672:Lig4	UTSW	8	10,023,213 (GRCm39)	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- TTGCACATCTGTCCCGAACG -3'
(R):5'- TCAAAGACTTAAAGCTTGGCATCAG -3'

Sequencing Primer
(F):5'- TGTCCCGAACGCATTGTG -3'
(R):5'- GACTTAAAGCTTGGCATCAGTCAGC -3'

Posted On

2016-06-21