Mutagenetix > Incidental Mutation

Incidental Mutation 'R2026:Lig4'

220623

Institutional Source

Beutler Lab

Gene Symbol

Lig4

Ensembl Gene

ENSMUSG00000049717

Gene Name

ligase IV, DNA, ATP-dependent

Synonyms

DNA ligase IV, 5830471N16Rik, tiny

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R2026 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

9969049-9977686 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 9972436 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Glutamine at position 448 (L448Q)

Ref Sequence

ENSEMBL: ENSMUSP00000130807 (fasta)

Gene Model

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

AlphaFold

Q8BTF7

Predicted Effect

probably damaging
Transcript: ENSMUST00000095476
AA Change: L448Q

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: L448Q

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: L448Q

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: L448Q

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: 99.4%
3x: 98.7%
10x: 97.3%
20x: 95.3%

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
6430548M08Rik	A	G	8: 120,153,466	K269R	probably benign	Het
Abcc12	A	G	8: 86,558,233	V251A	probably benign	Het
Avil	G	A	10: 127,011,873	G556S	probably damaging	Het
C3	T	C	17: 57,218,562	Y898C	probably damaging	Het
Cacng2	A	G	15: 77,995,520	F201L	possibly damaging	Het
Casp7	T	A	19: 56,436,398	I183N	probably damaging	Het
Cntn3	A	T	6: 102,420,427	W62R	probably damaging	Het
Ctrb1	T	C	8: 111,688,685	N119S	probably benign	Het
Cyp3a59	G	A	5: 146,096,288	V157M	probably damaging	Het
Dhfr	G	T	13: 92,365,771	G117*	probably null	Het
Dido1	A	T	2: 180,689,181	L158*	probably null	Het
Dlg2	C	A	7: 91,965,723	P290Q	probably damaging	Het
Dnah3	T	A	7: 120,039,406	Q1240L	probably damaging	Het
Exd1	A	T	2: 119,520,305	S492T	probably benign	Het
Fermt1	T	C	2: 132,918,525	I415M	probably benign	Het
Fsip2	A	G	2: 82,989,444	T5174A	possibly damaging	Het
Fuca2	T	G	10: 13,512,647	V389G	probably damaging	Het
Gm14412	A	T	2: 177,317,105	H50Q	possibly damaging	Het
Gm14685	G	T	X: 73,127,655	G218C	probably damaging	Het
Gm5129	G	A	5: 29,735,734		probably benign	Het
Hif3a	T	C	7: 17,044,397	R437G	possibly damaging	Het
Hook3	T	C	8: 26,038,098	E588G	probably damaging	Het
Hs1bp3	A	G	12: 8,337,738	E301G	probably benign	Het
Icam2	A	G	11: 106,382,442	F15L	probably benign	Het
Ice2	T	C	9: 69,416,325	S701P	probably benign	Het
Igf2bp1	A	G	11: 95,974,170	V151A	possibly damaging	Het
Man2b1	G	C	8: 85,095,335	W726C	probably damaging	Het
Mepe	T	C	5: 104,327,091	S13P	possibly damaging	Het
Msh6	C	T	17: 87,990,343	H1264Y	probably damaging	Het
Ncoa1	A	T	12: 4,267,647	S1228R	probably benign	Het
Ndufa10	A	G	1: 92,439,892	Y339H	probably damaging	Het
Nup155	A	T	15: 8,157,760	H1391L	probably damaging	Het
Nutm2	A	G	13: 50,474,820	H640R	probably benign	Het
Olfr1133	G	T	2: 87,645,409	A238E	probably damaging	Het
Olfr1487	T	A	19: 13,619,581	C140S	probably damaging	Het
Olfr266	T	C	3: 106,821,711	I283V	probably benign	Het
Olfr31	T	C	14: 14,328,891	V260A	probably benign	Het
Olfr616	T	A	7: 103,564,877	Y134F	probably damaging	Het
Olfr801	T	A	10: 129,670,465	D18V	probably damaging	Het
Pde1c	C	T	6: 56,180,190	V162I	probably damaging	Het
Pdss2	A	T	10: 43,393,875	N238I	possibly damaging	Het
Pfas	C	T	11: 68,993,957	G473E	probably damaging	Het
Pkn1	A	G	8: 83,671,378	V795A	probably damaging	Het
Polq	A	G	16: 37,062,745	D1757G	possibly damaging	Het
Popdc3	T	C	10: 45,314,855	W21R	probably damaging	Het
Ptch1	T	G	13: 63,524,959	E944A	probably benign	Het
Ptpro	T	A	6: 137,443,594	V1007D	probably damaging	Het
Rfc1	G	T	5: 65,288,029	T412K	probably damaging	Het
Sap130	T	C	18: 31,698,574	S706P	possibly damaging	Het
Scgn	T	C	13: 23,991,064		probably benign	Het
Smad7	T	C	18: 75,394,154	V357A	probably damaging	Het
Snrnp48	G	T	13: 38,209,886	A56S	possibly damaging	Het
Sptbn1	G	T	11: 30,104,559	A2178E	probably benign	Het
Syn2	C	T	6: 115,278,251	T508I	probably benign	Het
Tedc2	T	A	17: 24,216,317	E366V	probably damaging	Het
Tedc2	C	A	17: 24,216,318	E366*	probably null	Het
Tmtc4	T	C	14: 122,921,265	N682S	probably benign	Het
Trpm7	T	C	2: 126,812,738	K1427E	probably benign	Het
Trrap	A	G	5: 144,803,044	I1118V	possibly damaging	Het
Tslp	A	T	18: 32,815,672	I37L	probably benign	Het
Ttll3	G	A	6: 113,398,770	V297M	probably damaging	Het
Ttn	T	C	2: 76,710,369	D34091G	possibly damaging	Het
Txndc11	CCCGCCGCCGCCGCCGC	CCCGCCGCCGCCGC	16: 11,134,474		probably benign	Het
Ube3a	T	C	7: 59,303,726	F803L	probably damaging	Het
Ubn1	A	G	16: 5,064,650	E325G	probably damaging	Het
Wfikkn2	A	G	11: 94,238,953	W121R	possibly damaging	Het
Zfp579	C	A	7: 4,993,521	E464*	probably null	Het
Zfp616	A	T	11: 74,083,587	L227F	possibly 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
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
R9165:Lig4	UTSW	8	9972394	missense	probably damaging	1.00
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'- GCCAATTTCAAGCCCAGGTC -3'
(R):5'- CTTAGTAGCACTTTCACACCCATAC -3'

Sequencing Primer
(F):5'- TTCAAGCCCAGGTCATAGAGTTC -3'
(R):5'- CCATACAAGGCCGCATAGAAATAGTG -3'

Posted On

2014-08-25