Mutagenetix > Incidental Mutations

Incidental Mutation 'R1566:Lig4'

175272

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

039605-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R1566 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

9969049-9977686 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 9973650 bp

Zygosity

Heterozygous

Amino Acid Change

Leucine to Phenylalanine at position 43 (L43F)

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: L43F

PolyPhen 2 Score 0.409 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: L43F

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: L43F

PolyPhen 2 Score 0.409 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: L43F

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: 99.0%
3x: 98.1%
10x: 95.7%
20x: 90.9%

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: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700012B07Rik	T	A	11: 109,788,806	I247F	probably benign	Het
Afap1l1	T	C	18: 61,755,643	N119S	probably benign	Het
Ap2a1	T	C	7: 44,903,480	D721G	probably benign	Het
Ap3m2	C	T	8: 22,803,951	V28M	probably damaging	Het
Arhgef7	A	G	8: 11,782,620	T32A	possibly damaging	Het
Avl9	C	T	6: 56,736,482	R242*	probably null	Het
Bsn	G	A	9: 108,125,985	T407I	probably benign	Het
Capn3	A	T	2: 120,502,993	R627S	possibly damaging	Het
Car13	G	A	3: 14,650,698	R92Q	probably benign	Het
Clcn1	T	C	6: 42,291,440	I149T	possibly damaging	Het
Col1a2	G	T	6: 4,523,613	G514V	probably damaging	Het
Ctsw	C	A	19: 5,465,417	C347F	probably damaging	Het
Dna2	C	T	10: 62,949,187	R28W	probably benign	Het
Eml1	T	A	12: 108,471,892	V97D	probably damaging	Het
Epb41l1	A	G	2: 156,521,959	E796G	probably benign	Het
Gdnf	A	G	15: 7,834,414	K102R	probably benign	Het
Gm1110	T	C	9: 26,880,870	E618G	probably damaging	Het
Gm8300	A	T	12: 87,517,231	H112L	probably benign	Het
Gmnc	T	C	16: 26,963,939	D22G	probably damaging	Het
Greb1	T	C	12: 16,711,828	D517G	possibly damaging	Het
Gsta1	A	T	9: 78,242,459	K185*	probably null	Het
Ift88	A	G	14: 57,441,011	D160G	probably benign	Het
Intu	T	A	3: 40,692,578	I627N	probably damaging	Het
Itgav	T	A	2: 83,736,630	F101L	probably damaging	Het
Kars	C	T	8: 111,997,658	V475I	probably benign	Het
Klra3	G	C	6: 130,333,144	R138G	probably benign	Het
Klra7	A	G	6: 130,231,601	V6A	probably damaging	Het
Krtap6-2	A	G	16: 89,419,738	S114P	unknown	Het
Ldlrad4	T	C	18: 68,250,598	S122P	probably benign	Het
Mfsd4a	T	C	1: 132,059,179	D137G	probably damaging	Het
Mmel1	C	T	4: 154,883,653	R149C	probably damaging	Het
Morc2b	T	A	17: 33,136,974	H608L	probably benign	Het
Mrgpra6	G	A	7: 47,188,904	T182I	probably benign	Het
Nat8l	C	A	5: 34,000,856	N203K	probably benign	Het
Nin	A	T	12: 70,054,479	V448E	probably damaging	Het
Olfr1053	G	A	2: 86,314,785	T167I	probably benign	Het
Olfr164	T	A	16: 19,286,327	M139L	possibly damaging	Het
Olfr17	T	G	7: 107,097,552	F29C	probably damaging	Het
Olfr178	T	A	16: 58,889,540	I227F	probably damaging	Het
Pank4	T	C	4: 154,980,521	L759P	probably damaging	Het
Pcm1	T	A	8: 41,290,773	N1152K	probably damaging	Het
Pitpnm3	A	T	11: 72,058,959		probably null	Het
Plekhg3	T	C	12: 76,572,065	M497T	possibly damaging	Het
Ppfia3	T	C	7: 45,340,688	D1138G	probably damaging	Het
Prl6a1	T	A	13: 27,315,427	S59R	possibly damaging	Het
Pth2r	A	G	1: 65,388,538	S457G	possibly damaging	Het
Rbm25	T	A	12: 83,675,054	N671K	probably damaging	Het
Rbm26	T	A	14: 105,160,544	K47N	unknown	Het
Ryr1	T	A	7: 29,092,175	I1435F	possibly damaging	Het
Scin	T	A	12: 40,081,674	H287L	probably benign	Het
Serpinb9e	T	C	13: 33,253,494	L120P	probably damaging	Het
Slc34a1	A	C	13: 55,412,031		probably null	Het
Slc39a10	A	G	1: 46,836,085	F19S	possibly damaging	Het
Sos1	A	G	17: 80,453,916	V117A	probably damaging	Het
Spta1	C	A	1: 174,184,706	N359K	probably benign	Het
Sspo	G	A	6: 48,466,870		probably null	Het
Stx5a	T	A	19: 8,742,311	D13E	probably damaging	Het
Supt16	G	A	14: 52,176,655	A489V	probably damaging	Het
Tap1	T	A	17: 34,189,546	L253Q	probably benign	Het
Tmc6	A	G	11: 117,769,436	S659P	probably damaging	Het
Tnfsf14	T	C	17: 57,193,876	D65G	probably benign	Het
Ttc28	G	A	5: 111,225,677	S962N	probably damaging	Het
Ugt8a	T	C	3: 125,875,558	Y299C	probably damaging	Het
Upk1a	A	G	7: 30,609,720	V59A	possibly damaging	Het
Usp38	T	C	8: 80,984,803	T868A	probably benign	Het
Wdsub1	G	A	2: 59,876,715	H58Y	probably damaging	Het
Zc3h7b	T	C	15: 81,768,834	S19P	possibly damaging	Het
Zfp385b	A	C	2: 77,415,913	F257V	probably benign	Het
Zmym4	A	C	4: 126,911,147	I188S	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
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
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

Predicted Primers

PCR Primer
(F):5'- TGCAATCATGGCAAAGTCCCCAG -3'
(R):5'- CAAACCGGAGGATTTGTTGTCGC -3'

Sequencing Primer
(F):5'- AGCTTCTGGGCATCCTTG -3'
(R):5'- GCTTCTATGGCTTCCTCACAAAC -3'

Posted On

2014-04-24