Mutagenetix > Incidental Mutations

Incidental Mutation 'R2155:Lig4'

234724

Institutional Source

Beutler Lab

Gene Symbol

Lig4

Ensembl Gene

ENSMUSG00000049717

Gene Name

ligase IV, DNA, ATP-dependent

Synonyms

DNA ligase IV, 5830471N16Rik, tiny

MMRRC Submission

040158-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R2155 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

9969049-9977686 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 9972766 bp

Zygosity

Heterozygous

Amino Acid Change

Threonine to Isoleucine at position 338 (T338I)

Ref Sequence

ENSEMBL: ENSMUSP00000130807 (fasta)

Gene Model

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

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

probably benign
Transcript: ENSMUST00000095476
AA Change: T338I

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: T338I

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

probably benign
Transcript: ENSMUST00000170033
AA Change: T338I

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: T338I

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: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.4%

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: 89 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2610318N02Rik	A	G	16: 17,121,396	L41P	probably damaging	Het
Aff4	C	T	11: 53,399,619	L469F	probably damaging	Het
AI182371	G	A	2: 35,085,354	H288Y	probably benign	Het
AK157302	A	T	13: 21,495,657	K118*	probably null	Het
Arhgef2	G	A	3: 88,636,044	R454Q	probably damaging	Het
Asb17	C	T	3: 153,844,685	T118M	probably damaging	Het
Atp7b	A	G	8: 22,013,584	V718A	possibly damaging	Het
BC003331	A	G	1: 150,382,335	V183A	possibly damaging	Het
Cdca2	A	G	14: 67,714,838	L28S	probably damaging	Het
Cdh7	G	T	1: 110,048,864	L86F	probably damaging	Het
Cela2a	A	T	4: 141,818,039		probably null	Het
Cers3	T	A	7: 66,783,414	Y160N	probably damaging	Het
Chmp2b	A	G	16: 65,546,991	V56A	probably benign	Het
Cryl1	A	G	14: 57,398,423	V9A	unknown	Het
Dmbt1	A	T	7: 131,097,575	H978L	possibly damaging	Het
Dnm1	C	T	2: 32,314,937	V673M	probably damaging	Het
Dtx4	T	A	19: 12,485,282	K378*	probably null	Het
Extl1	A	T	4: 134,363,180	M328K	possibly damaging	Het
Fcgbp	T	C	7: 28,107,203	S2199P	probably benign	Het
Glis3	G	T	19: 28,531,302	N427K	probably benign	Het
Gm6614	T	C	6: 141,980,944	D552G	probably damaging	Het
Gm884	T	C	11: 103,620,459	T228A	unknown	Het
Hdac7	T	C	15: 97,794,063	K810E	probably benign	Het
Hesx1	A	G	14: 27,001,477	E88G	probably benign	Het
Hmcn2	A	T	2: 31,460,349	Q5086L	possibly damaging	Het
Ier3	A	G	17: 35,822,209	T128A	probably benign	Het
Igsf10	G	T	3: 59,331,680	T360K	probably damaging	Het
Ilkap	A	C	1: 91,384,623	C2G	possibly damaging	Het
Itih1	A	G	14: 30,938,071	F231S	probably damaging	Het
Jrkl	A	T	9: 13,244,908	Y249*	probably null	Het
Kat6a	AGAGGAGGAGGAGGAGGAGGAGGAG	AGAGGAGGAGGAGGAGGAGGAG	8: 22,935,647		probably benign	Het
Katnal2	A	T	18: 77,010,941	S184R	probably benign	Het
Kcnh5	T	A	12: 74,898,456		probably null	Het
Kcnj11	G	T	7: 46,099,357	L181I	probably damaging	Het
Klhl2	T	C	8: 64,749,770	T465A	probably benign	Het
Krt90	T	A	15: 101,562,611	Y72F	probably benign	Het
Magel2	T	C	7: 62,380,792	V1148A	unknown	Het
Mak	C	A	13: 41,032,544	E549D	probably benign	Het
Marf1	G	T	16: 14,132,429	S1001Y	probably damaging	Het
Mcoln1	G	A	8: 3,511,787	V446I	probably damaging	Het
Meig1	T	C	2: 3,409,253	N70S	probably benign	Het
Mfsd14a	G	A	3: 116,647,830	T108I	probably damaging	Het
Mocs1	G	A	17: 49,454,358	M493I	probably damaging	Het
Mrpl11	C	A	19: 4,962,469	A26E	probably damaging	Het
Myh6	A	T	14: 54,953,794	D863E	probably benign	Het
Myom2	T	A	8: 15,084,555	Y453N	probably damaging	Het
Nhlh1	A	G	1: 172,053,957	I114T	probably damaging	Het
Olfr131	G	T	17: 38,082,180	P266Q	probably damaging	Het
Olfr181	G	T	16: 58,926,123	F149L	probably benign	Het
Olfr508	C	G	7: 108,630,777	P262A	probably damaging	Het
Olfr533	A	C	7: 140,466,591	H130P	probably benign	Het
Olfr729	A	T	14: 50,148,697	M59K	probably damaging	Het
Pclo	T	C	5: 14,714,295	S976P	probably benign	Het
Pde3a	G	A	6: 141,483,914	E734K	possibly damaging	Het
Pdzd2	A	T	15: 12,375,793	S1419T	probably benign	Het
Pdzd8	T	A	19: 59,300,421	Y849F	probably damaging	Het
Phldb3	A	G	7: 24,612,645	E128G	probably damaging	Het
Polg	A	G	7: 79,461,720	I261T	possibly damaging	Het
Ppp1r35	T	C	5: 137,780,005	M254T	probably benign	Het
Ppp3ca	G	T	3: 136,890,450	R292M	possibly damaging	Het
Ptk7	T	A	17: 46,579,617	T430S	probably benign	Het
Ptrh1	T	A	2: 32,777,028	N144K	possibly damaging	Het
Rbfox1	A	G	16: 7,294,082	T211A	possibly damaging	Het
Rbpjl	A	G	2: 164,414,423	D443G	possibly damaging	Het
Rcc1	A	G	4: 132,338,049		probably null	Het
Rimbp2	G	T	5: 128,788,165	S706R	probably damaging	Het
Rsph10b	G	C	5: 143,961,256	E96D	probably benign	Het
Scn10a	A	T	9: 119,609,448	I1784K	probably benign	Het
Sfxn2	A	G	19: 46,591,546		probably null	Het
Slamf6	T	A	1: 171,938,008	L233Q	probably damaging	Het
Slc17a5	A	T	9: 78,577,173	Y102N	probably damaging	Het
Slc25a53	T	C	X: 136,983,467	T42A	probably damaging	Het
Smg7	G	A	1: 152,840,313	T1057I	possibly damaging	Het
Speer2	T	A	16: 69,860,597	T53S	possibly damaging	Het
Srm	A	C	4: 148,592,491	I100L	probably benign	Het
Stoml3	A	C	3: 53,507,587	N267H	probably damaging	Het
Thsd7a	A	C	6: 12,379,633	C931G	probably damaging	Het
Tlr11	A	G	14: 50,360,682	I42V	probably benign	Het
Tmigd1	T	C	11: 76,910,173	V162A	probably benign	Het
Tmx3	A	G	18: 90,510,381		probably null	Het
Topors	T	A	4: 40,262,790	R165W	possibly damaging	Het
Ttc17	A	T	2: 94,366,642	S453R	possibly damaging	Het
Vmn1r49	G	T	6: 90,072,459	T187N	probably damaging	Het
Zbtb49	A	T	5: 38,214,120	V139E	possibly damaging	Het
Zfp11	T	C	5: 129,657,152	H415R	probably damaging	Het
Zfp677	A	T	17: 21,397,708	K342N	probably benign	Het
Zfp979	A	C	4: 147,613,458	C265G	possibly damaging	Het
Zfpl1	T	C	19: 6,084,429	R9G	probably damaging	Het
Zkscan8	A	T	13: 21,520,589	C321*	probably null	Het

Other mutations in Lig4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00229:Lig4	APN	8	9972775	missense	probably damaging	1.00
IGL00655:Lig4	APN	8	9973305	missense	probably benign	0.09
IGL01388:Lig4	APN	8	9973586	missense	probably damaging	1.00
IGL01669:Lig4	APN	8	9973673	missense	probably benign	0.01
IGL01757:Lig4	APN	8	9971185	missense	probably benign	0.10
IGL02115:Lig4	APN	8	9973247	missense	possibly damaging	0.58
IGL02167:Lig4	APN	8	9971821	missense	probably benign	0.06
IGL02239:Lig4	APN	8	9972473	missense	probably damaging	1.00
IGL02576:Lig4	APN	8	9971116	missense	probably damaging	1.00
IGL02955:Lig4	APN	8	9972103	missense	possibly damaging	0.95
IGL03056:Lig4	APN	8	9972580	missense	possibly damaging	0.90
posey	UTSW	8	9972955	missense	probably damaging	1.00
posey2	UTSW	8	9971585	missense	probably benign
R0791:Lig4	UTSW	8	9973012	missense	possibly damaging	0.70
R1208:Lig4	UTSW	8	9971062	missense	probably damaging	1.00
R1208:Lig4	UTSW	8	9971062	missense	probably damaging	1.00
R1368:Lig4	UTSW	8	9971176	missense	possibly damaging	0.89
R1522:Lig4	UTSW	8	9973012	missense	possibly damaging	0.70
R1566:Lig4	UTSW	8	9973650	missense	probably benign	0.41
R1674:Lig4	UTSW	8	9971692	missense	probably benign	0.01
R2024:Lig4	UTSW	8	9972436	missense	probably damaging	1.00
R2025:Lig4	UTSW	8	9972436	missense	probably damaging	1.00
R2026:Lig4	UTSW	8	9972436	missense	probably damaging	1.00
R2243:Lig4	UTSW	8	9972161	missense	possibly damaging	0.81
R2917:Lig4	UTSW	8	9971596	missense	possibly damaging	0.56
R4763:Lig4	UTSW	8	9972955	missense	probably damaging	1.00
R4819:Lig4	UTSW	8	9971885	missense	probably benign
R5153:Lig4	UTSW	8	9973003	missense	possibly damaging	0.95
R5397:Lig4	UTSW	8	9972644	missense	probably benign	0.01
R5618:Lig4	UTSW	8	9972021	missense	probably benign
R6102:Lig4	UTSW	8	9972872	missense	probably damaging	1.00
R6210:Lig4	UTSW	8	9971585	missense	probably benign
R6312:Lig4	UTSW	8	9971739	missense	probably benign
R6955:Lig4	UTSW	8	9973384	missense	probably damaging	1.00
R6991:Lig4	UTSW	8	9971098	missense	probably damaging	0.99
R7207:Lig4	UTSW	8	9972101	nonsense	probably null
R7769:Lig4	UTSW	8	9973629	missense	possibly damaging	0.92

Predicted Primers

PCR Primer
(F):5'- AGTTTTCTGCACTATTTCTATGCGG -3'
(R):5'- AGCTTGATGGTGAGCGCATG -3'

Sequencing Primer
(F):5'- CACTATTTCTATGCGGCCTTGTATGG -3'
(R):5'- TGGTGAGCGCATGCAGATG -3'

Posted On

2014-10-01