Mutagenetix > Incidental Mutation

Incidental Mutation 'R1674:Lig4'

187918

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

039710-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1674 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

10020020-10027680 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 10021692 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 696 (D696G)

Ref Sequence

ENSEMBL: ENSMUSP00000130807 (fasta)

Gene Model

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

AlphaFold

Q8BTF7

Predicted Effect

probably benign
Transcript: ENSMUST00000095476
AA Change: D696G

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: D696G

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: ENSMUST00000170033
AA Change: D696G

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: D696G

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

Meta Mutation Damage Score

0.1592

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 94.1%

Validation Efficiency

100% (91/91)

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
4930579G24Rik	A	G	3: 79,538,451 (GRCm39)	T66A	probably benign	Het
5430401F13Rik	A	T	6: 131,529,766 (GRCm39)	Q120L	unknown	Het
Akirin1	A	G	4: 123,637,256 (GRCm39)	S110P	possibly damaging	Het
Ankmy2	T	A	12: 36,237,668 (GRCm39)	S256T	probably benign	Het
Areg	T	C	5: 91,291,485 (GRCm39)	F143L	probably damaging	Het
Arhgap42	A	G	9: 9,006,585 (GRCm39)	S604P	probably damaging	Het
Arid1a	A	G	4: 133,416,571 (GRCm39)	V1068A	unknown	Het
Arid4a	G	A	12: 71,122,112 (GRCm39)	S509N	probably benign	Het
Atoh1	T	G	6: 64,706,914 (GRCm39)	I203S	possibly damaging	Het
Atp5mg	T	C	9: 44,825,957 (GRCm39)	T69A	possibly damaging	Het
Baz1b	A	G	5: 135,233,965 (GRCm39)	E164G	probably damaging	Het
Baz2b	A	T	2: 59,743,336 (GRCm39)	V1545E	possibly damaging	Het
Best1	A	G	19: 9,970,590 (GRCm39)		probably null	Het
Casp8	T	A	1: 58,883,575 (GRCm39)	I314N	probably damaging	Het
Ccdc13	T	C	9: 121,638,208 (GRCm39)	T26A	probably damaging	Het
Ccr6	A	T	17: 8,475,049 (GRCm39)	I85L	probably damaging	Het
Cdh10	A	T	15: 18,985,152 (GRCm39)	N272I	probably benign	Het
Cdh10	T	A	15: 19,013,416 (GRCm39)	I672K	probably damaging	Het
Cdk17	A	T	10: 93,057,492 (GRCm39)	E163V	probably benign	Het
Chsy1	T	C	7: 65,821,411 (GRCm39)	F549L	probably damaging	Het
CN725425	T	C	15: 91,131,124 (GRCm39)	Y420H	possibly damaging	Het
Cpt1b	A	T	15: 89,306,535 (GRCm39)	M281K	possibly damaging	Het
Crlf2	A	G	5: 109,706,669 (GRCm39)		probably null	Het
Ctif	T	C	18: 75,770,251 (GRCm39)	T45A	probably benign	Het
Ddx31	T	C	2: 28,748,828 (GRCm39)	F252S	probably damaging	Het
Dennd2d	T	C	3: 106,399,833 (GRCm39)	I242T	probably benign	Het
Dennd5b	A	G	6: 148,899,782 (GRCm39)	F1205S	probably damaging	Het
Dop1a	T	C	9: 86,418,213 (GRCm39)	S1981P	probably damaging	Het
Dsg1b	A	T	18: 20,532,578 (GRCm39)	T541S	probably benign	Het
Dst	T	A	1: 34,262,876 (GRCm39)		probably null	Het
Dysf	T	C	6: 84,156,697 (GRCm39)	V1508A	probably benign	Het
Erf	A	T	7: 24,944,731 (GRCm39)	L200Q	possibly damaging	Het
Erich3	A	G	3: 154,468,260 (GRCm39)		probably benign	Het
Esrrb	C	T	12: 86,561,225 (GRCm39)	L320F	probably damaging	Het
Fap	T	A	2: 62,349,349 (GRCm39)	D508V	probably benign	Het
Fdft1	A	C	14: 63,402,034 (GRCm39)	N48K	probably benign	Het
Fdps	A	G	3: 89,008,037 (GRCm39)	V94A	probably benign	Het
Fes	A	T	7: 80,027,686 (GRCm39)	H819Q	probably benign	Het
Foxd1	G	T	13: 98,491,347 (GRCm39)	D74Y	unknown	Het
Gm136	A	T	4: 34,746,662 (GRCm39)		probably benign	Het
Gm5919	T	A	9: 83,765,338 (GRCm39)	L58*	probably null	Het
Gm6871	C	T	7: 41,223,059 (GRCm39)	V10I	possibly damaging	Het
Isy1	T	C	6: 87,811,469 (GRCm39)	R29G	probably damaging	Het
Kif16b	T	A	2: 142,554,873 (GRCm39)	K653*	probably null	Het
Kif17	A	G	4: 138,028,569 (GRCm39)	T706A	probably benign	Het
Kif18b	G	T	11: 102,803,886 (GRCm39)	P425T	probably benign	Het
Lama1	T	A	17: 68,098,239 (GRCm39)	V1812E	probably benign	Het
Lama5	A	G	2: 179,843,780 (GRCm39)	V430A	probably benign	Het
Lclat1	A	G	17: 73,546,776 (GRCm39)	E231G	probably damaging	Het
Mylpf	T	A	7: 126,813,309 (GRCm39)	V151E	probably damaging	Het
Naa16	A	T	14: 79,624,497 (GRCm39)	M1K	probably null	Het
Ndufaf6	T	C	4: 11,070,264 (GRCm39)	K119R	probably benign	Het
Nt5c1b	T	C	12: 10,420,055 (GRCm39)		probably benign	Het
Or14a260	G	A	7: 85,984,765 (GRCm39)	P280S	probably damaging	Het
Or4a27	A	G	2: 88,559,601 (GRCm39)	V114A	probably damaging	Het
Or5t17	T	C	2: 86,832,577 (GRCm39)	V88A	probably benign	Het
Or8k33	T	A	2: 86,384,204 (GRCm39)	D88V	probably damaging	Het
Or9i16	T	A	19: 13,864,954 (GRCm39)	I207L	probably benign	Het
Otud4	A	G	8: 80,399,776 (GRCm39)	N830S	probably benign	Het
Pdcd10	A	C	3: 75,448,486 (GRCm39)	M26R	probably damaging	Het
Pitpnc1	A	G	11: 107,117,071 (GRCm39)	V223A	possibly damaging	Het
Pkp2	A	G	16: 16,058,422 (GRCm39)	D368G	possibly damaging	Het
Pla1a	A	T	16: 38,235,172 (GRCm39)	M174K	probably benign	Het
Polr2b	A	G	5: 77,474,470 (GRCm39)	K436E	possibly damaging	Het
Pwwp4a	G	T	X: 72,171,261 (GRCm39)	G218C	probably damaging	Het
Rdh16	A	G	10: 127,637,226 (GRCm39)	M54V	probably benign	Het
Sall2	C	A	14: 52,551,293 (GRCm39)	C632F	probably damaging	Het
Sart1	T	A	19: 5,435,853 (GRCm39)	I120F	probably damaging	Het
Slco1a1	A	T	6: 141,881,661 (GRCm39)	M157K	probably damaging	Het
Snapc4	T	C	2: 26,266,209 (GRCm39)	T178A	probably benign	Het
Sox6	T	C	7: 115,400,654 (GRCm39)	I63V	probably benign	Het
Spin1	T	A	13: 51,303,135 (GRCm39)	Y243N	probably damaging	Het
Stmnd1	T	C	13: 46,453,097 (GRCm39)	Y258H	possibly damaging	Het
Tex13b	A	T	X: 139,710,819 (GRCm39)	N184K	probably benign	Het
Tgm5	T	C	2: 120,902,025 (GRCm39)	T215A	possibly damaging	Het
Tnks2	A	G	19: 36,849,022 (GRCm39)	T165A	probably benign	Het
Top2a	A	T	11: 98,900,099 (GRCm39)	F667Y	probably damaging	Het
Tpo	T	C	12: 30,150,567 (GRCm39)	M438V	probably benign	Het
Tyw1	A	G	5: 130,298,169 (GRCm39)	R237G	probably benign	Het
Unc5c	G	A	3: 141,463,598 (GRCm39)	V240I	possibly damaging	Het
Unc80	A	C	1: 66,548,467 (GRCm39)	T580P	probably damaging	Het
Upp2	G	A	2: 58,680,076 (GRCm39)	E301K	probably benign	Het
Utp18	A	G	11: 93,766,879 (GRCm39)		probably null	Het
Vmn1r23	T	C	6: 57,903,046 (GRCm39)	D244G	possibly damaging	Het
Vps13c	T	A	9: 67,760,985 (GRCm39)	L51*	probably null	Het
Xpnpep3	A	G	15: 81,314,968 (GRCm39)	T223A	probably benign	Het
Zfp28	T	A	7: 6,397,942 (GRCm39)	H792Q	possibly damaging	Het
Zfp804a	A	G	2: 82,089,168 (GRCm39)	K999R	probably benign	Het
Zkscan16	G	A	4: 58,948,918 (GRCm39)	V158M	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
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
R5153:Lig4	UTSW	8	10,023,003 (GRCm39)	missense	possibly damaging	0.95
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'- TGAATCATAAAGCGAGGTTGCCACG -3'
(R):5'- AAGCATCTGGGAAGCTTGCCAC -3'

Sequencing Primer
(F):5'- CACGGCACGCATGTTTTTG -3'
(R):5'- CGAAACACCTTCATGTAGGTGATG -3'

Posted On

2014-05-09