Mutagenetix > Incidental Mutation

Incidental Mutation 'R9165:Lig4'

695995

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

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R9165 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

9969049-9977686 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 9972394 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Serine at position 462 (L462S)

Ref Sequence

ENSEMBL: ENSMUSP00000093130 (fasta)

Gene Model

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

AlphaFold

Q8BTF7

Predicted Effect

probably damaging
Transcript: ENSMUST00000095476
AA Change: L462S

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

SMART Domains

Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: L462S

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 damaging
Transcript: ENSMUST00000170033
AA Change: L462S

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

SMART Domains

Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: L462S

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: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.2%

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610010F05Rik	T	C	11: 23,615,244	I248V	probably benign	Het
1700122O11Rik	T	C	17: 48,037,548	I27V	probably benign	Het
A2ml1	T	A	6: 128,560,669	H693L	probably benign	Het
Acacb	A	G	5: 114,216,683	E1206G	probably benign	Het
Acoxl	A	G	2: 127,884,512	T269A	probably benign	Het
Ak9	A	G	10: 41,433,239	K1879R	unknown	Het
Amot	A	T	X: 145,461,749	L435H		Het
Bnc2	A	T	4: 84,411,494	L95Q		Het
Bpifa2	G	T	2: 154,009,821	W59L	probably benign	Het
Cd209a	T	A	8: 3,745,602	Q156H	probably damaging	Het
Cep104	T	A	4: 153,994,514		probably null	Het
Cpt1c	A	G	7: 44,959,501	*799R	probably null	Het
Csn2	A	T	5: 87,694,559	M203K	possibly damaging	Het
Dclre1a	C	G	19: 56,538,369	A872P	probably damaging	Het
Dlg5	C	A	14: 24,146,241	L1629F	probably damaging	Het
Dmxl1	A	G	18: 49,878,925	D1383G	probably damaging	Het
Dnah6	A	G	6: 73,144,941	V1381A	probably damaging	Het
Dnttip2	G	T	3: 122,276,706	E523D	probably benign	Het
Dync2h1	A	T	9: 7,114,883	V2425D	probably damaging	Het
Eif2a	G	A	3: 58,545,274	R199Q	probably damaging	Het
F10	T	C	8: 13,039,564	F60L	probably benign	Het
Faf2	A	G	13: 54,652,138	I253V	probably benign	Het
Fam71a	A	G	1: 191,163,061	S462P	probably benign	Het
Flt1	T	A	5: 147,615,237	S715C	probably damaging	Het
Gm2056	A	G	12: 88,027,307	S102G	possibly damaging	Het
Gm5150	G	T	3: 15,990,896	T55K	probably damaging	Het
Gria1	T	C	11: 57,185,933	F121L	possibly damaging	Het
Gucy2d	A	G	7: 98,454,064	Q505R	probably benign	Het
Gzma	A	T	13: 113,100,921	S11T	probably benign	Het
Hoxa6	G	A	6: 52,208,555	Q24*	probably null	Het
Kcnj14	T	A	7: 45,819,644	I146L	possibly damaging	Het
Kiss1r	G	A	10: 79,920,771	R149H	probably damaging	Het
Lama2	A	G	10: 27,053,026		probably null	Het
Lama5	C	A	2: 180,179,493	R3092L	probably damaging	Het
Lca5l	T	A	16: 96,176,018	N196I	probably damaging	Het
Nbea	A	T	3: 56,004,868	V1166E	probably benign	Het
Nr2c1	T	A	10: 94,181,603	F401Y	probably benign	Het
Olfr1335	T	A	4: 118,808,998	R289*	probably null	Het
Olfr1431	A	T	19: 12,209,922	M119L	probably damaging	Het
Olfr1507	A	G	14: 52,490,373	I197T	possibly damaging	Het
Olfr299	A	T	7: 86,465,617	M69L	probably benign	Het
Otop3	A	C	11: 115,344,598	Y352S	possibly damaging	Het
Plekha6	T	G	1: 133,272,637	L318R	probably damaging	Het
Pm20d1	G	T	1: 131,816,087	V497F	possibly damaging	Het
Pnma2	G	A	14: 66,917,123	R332H	probably damaging	Het
Ppip5k1	C	A	2: 121,331,564	G1013C	probably damaging	Het
Prdm13	C	G	4: 21,679,659	R277P	unknown	Het
Prdm2	A	G	4: 143,132,104	S1539P	possibly damaging	Het
Ptger2	A	G	14: 44,989,778	T272A	probably damaging	Het
Qser1	T	C	2: 104,788,470	T576A	probably benign	Het
Rest	GGGGGCCTGCCCCTCCCACGGGGCCTGCCCCTCCCACGGGGCCTGCCCCTCCCACGGAGCCTGCCCCTCCCACGGGGC	GGGGGCCTGCCCCTCCCACGGGGCCTGCCCCTCCCACGGAGCCTGCCCCTCCCACGGGGC	5: 77,281,804		probably benign	Het
Sacm1l	G	T	9: 123,568,956	V238L	probably damaging	Het
Sec16a	C	T	2: 26,423,633	G454D		Het
Sil1	A	G	18: 35,317,846	S259P	possibly damaging	Het
Sirpb1b	A	G	3: 15,574,904	L16P	probably damaging	Het
Slc22a20	A	T	19: 5,982,851	V262D	probably damaging	Het
Slc4a9	G	T	18: 36,533,623	R580L	probably benign	Het
Ssr3	A	G	3: 65,383,100	V128A	probably damaging	Het
Stpg2	G	T	3: 139,309,232	S386I	possibly damaging	Het
Taar8c	C	A	10: 24,101,602	C104F	probably damaging	Het
Tex2	T	C	11: 106,567,269	E445G	unknown	Het
Tmem253	A	C	14: 52,018,642	D126A	probably benign	Het
Tox4	A	G	14: 52,285,790	Q69R	possibly damaging	Het
Tpi1	T	A	6: 124,811,538	S254C	probably benign	Het
Trmt12	T	G	15: 58,873,745	S331A	probably benign	Het
Ttn	A	G	2: 76,713,006	V33212A	probably damaging	Het
Tubb4a	C	T	17: 57,080,734	E431K	unknown	Het
Ugt1a10	A	T	1: 88,055,787	E102D	probably benign	Het
Unc80	A	T	1: 66,549,841	E1055V	probably null	Het
Vav1	C	A	17: 57,311,895	S708R	probably damaging	Het
Vmn1r20	A	G	6: 57,432,261	M191V	probably damaging	Het
Vmn1r37	A	T	6: 66,732,070	T227S	probably damaging	Het
Vmn1r72	C	A	7: 11,679,024		probably benign	Het
Vps33b	G	A	7: 80,274,686		probably null	Het
Vrtn	T	A	12: 84,650,477	L667Q	probably benign	Het
Xirp1	G	A	9: 120,018,236	T527M	probably benign	Het
Ylpm1	T	A	12: 85,030,568	Y1356N	probably damaging	Het
Zfp980	A	T	4: 145,701,454	Y251F	possibly damaging	Het
Zmym2	A	T	14: 56,948,007	Y1032F	probably damaging	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
nosegay	UTSW	8	9972954	missense	probably damaging	1.00
posey	UTSW	8	9972955	missense	probably damaging	1.00
posey2	UTSW	8	9971585	missense	probably benign
BB004:Lig4	UTSW	8	9973629	missense	possibly damaging	0.92
BB014:Lig4	UTSW	8	9973629	missense	possibly damaging	0.92
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
R2155:Lig4	UTSW	8	9972766	missense	probably benign	0.00
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
R7927:Lig4	UTSW	8	9973629	missense	possibly damaging	0.92
R8113:Lig4	UTSW	8	9973485	missense	probably benign	0.07
R8124:Lig4	UTSW	8	9972954	missense	probably damaging	1.00
R8382:Lig4	UTSW	8	9972346	missense	probably damaging	1.00
R8443:Lig4	UTSW	8	9973777	start codon destroyed	probably null	0.00
R8956:Lig4	UTSW	8	9971378	missense	probably benign
R9170:Lig4	UTSW	8	9972202	missense	probably damaging	1.00
R9356:Lig4	UTSW	8	9972538	missense	possibly damaging	0.94
R9535:Lig4	UTSW	8	9972325	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GAAAAGGCTTCCAGTATTTTGCC -3'
(R):5'- CAAGGCCGCATAGAAATAGTGC -3'

Sequencing Primer
(F):5'- TTGCCAATTTCAAGCCCAGG -3'
(R):5'- TAGTGCAGAAAACTCAAGCTCATAC -3'

Posted On

2022-02-07