Mutagenetix > Incidental Mutation

Incidental Mutation 'IGL00229:Lig4'

2320

Institutional Source

Australian Phenomics Network (link to record)

Gene Symbol

Lig4

Ensembl Gene

ENSMUSG00000049717

Gene Name

ligase IV, DNA, ATP-dependent

Synonyms

DNA ligase IV, 5830471N16Rik, tiny

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

IGL00229

Quality Score

Status

Chromosome

Chromosomal Location

9969049-9977686 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 9972775 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Cysteine at position 335 (Y335C)

Ref Sequence

ENSEMBL: ENSMUSP00000130807 (fasta)

Gene Model

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

AlphaFold

Q8BTF7

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 damaging
Transcript: ENSMUST00000095476
AA Change: Y335C

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

SMART Domains

Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: Y335C

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 damaging
Transcript: ENSMUST00000170033
AA Change: Y335C

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

SMART Domains

Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: Y335C

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

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
2010111I01Rik	A	G	13: 63,199,500		probably benign	Het
9030624J02Rik	T	A	7: 118,804,191		probably benign	Het
Abca4	A	G	3: 122,170,954	T929A	probably damaging	Het
Adam6b	G	A	12: 113,491,393	R610H	probably damaging	Het
Adamts12	T	A	15: 11,311,599	M1314K	probably benign	Het
Alg6	T	A	4: 99,753,054	F152I	probably damaging	Het
Arid5b	A	G	10: 68,128,975	S289P	probably damaging	Het
Axin1	T	C	17: 26,194,072	F780L	probably damaging	Het
C87499	A	G	4: 88,629,053	I214T	probably damaging	Het
C9	C	T	15: 6,483,231	S278L	possibly damaging	Het
Calr4	A	T	4: 109,244,115	I65F	probably damaging	Het
Cdh23	A	G	10: 60,523,548	V260A	probably benign	Het
Ddx25	T	C	9: 35,543,595		probably benign	Het
Dppa4	A	G	16: 48,291,083	T92A	possibly damaging	Het
Ercc5	T	C	1: 44,163,898	Y232H	probably damaging	Het
Exoc4	A	G	6: 33,918,399		probably null	Het
Fam149a	A	G	8: 45,351,786	V253A	probably damaging	Het
Fam209	C	T	2: 172,474,182	T159I	probably damaging	Het
Gcfc2	A	T	6: 81,936,015	N265I	probably damaging	Het
Glud1	T	C	14: 34,336,130	V366A	probably benign	Het
Hdac10	T	C	15: 89,128,442	T3A	probably damaging	Het
Ifnar1	T	C	16: 91,489,782	S54P	probably damaging	Het
Itpr2	T	C	6: 146,144,185	Y2561C	probably damaging	Het
Klhl30	A	G	1: 91,354,157	E160G	possibly damaging	Het
Kmt2d	A	T	15: 98,862,333	S1015T	unknown	Het
Lactb2	A	G	1: 13,660,374	M26T	probably damaging	Het
Lactbl1	A	T	4: 136,631,051	D111V	probably damaging	Het
Lrrc8e	T	A	8: 4,235,921	D715E	probably benign	Het
Med6	A	T	12: 81,579,574	V142D	possibly damaging	Het
Men1	G	A	19: 6,337,207		probably null	Het
Mettl13	A	G	1: 162,535,865	V600A	possibly damaging	Het
Mpdz	A	T	4: 81,310,224	C1314*	probably null	Het
Nbeal2	A	G	9: 110,635,869	V1009A	probably damaging	Het
Nmur2	A	G	11: 56,040,777	L36P	probably damaging	Het
Nudt2	T	A	4: 41,480,474	L119Q	probably damaging	Het
Olfr1472	T	C	19: 13,453,840	M226V	possibly damaging	Het
Osbpl3	C	T	6: 50,323,068	E519K	probably damaging	Het
Pak6	A	T	2: 118,689,845	T106S	possibly damaging	Het
Pggt1b	T	G	18: 46,280,719	Q34P	probably benign	Het
Phactr4	T	C	4: 132,370,992	T322A	possibly damaging	Het
Plekhj1	T	C	10: 80,796,602		probably null	Het
Pnpt1	T	C	11: 29,154,217		probably null	Het
Prr14l	T	C	5: 32,830,676	I492V	probably benign	Het
Ranbp2	C	A	10: 58,477,256	A1266E	probably damaging	Het
Riok3	G	A	18: 12,137,020	D140N	probably damaging	Het
Rsph4a	G	A	10: 33,914,343	E643K	probably damaging	Het
Scara3	T	G	14: 65,933,121	E103A	probably benign	Het
Sgk3	T	C	1: 9,868,384	V33A	probably damaging	Het
Slc38a4	A	G	15: 96,999,494	F480S	probably damaging	Het
Slc44a1	G	A	4: 53,543,571	V372M	probably damaging	Het
Slc9a2	A	G	1: 40,767,737	Y728C	probably benign	Het
Sox4	C	A	13: 28,952,973	G17W	probably damaging	Het
Spidr	A	T	16: 15,895,578	L847Q	probably damaging	Het
Sptb	A	G	12: 76,620,753	S857P	probably benign	Het
Syde1	A	G	10: 78,585,809	V636A	probably damaging	Het
Syna	A	G	5: 134,559,717	L126P	possibly damaging	Het
Taar2	A	G	10: 23,941,368	T269A	possibly damaging	Het
Tapbp	C	T	17: 33,925,704	T258I	probably damaging	Het
Tcf20	T	A	15: 82,857,142	Q36L	possibly damaging	Het
Tmem131l	A	T	3: 83,942,500	M260K	probably damaging	Het
Tnc	T	A	4: 64,016,824		probably benign	Het
Ugp2	T	A	11: 21,354,345	E27D	probably benign	Het
Wdr27	A	T	17: 14,928,310	C140*	probably null	Het
Wnt2b	T	C	3: 104,953,133	T153A	possibly damaging	Het
Xirp2	A	T	2: 67,513,375	T1987S	probably benign	Het
Zfp36l1	C	A	12: 80,110,464	G48C	probably damaging	Het
Zfp474	A	T	18: 52,638,493	I73F	possibly damaging	Het
Zfp790	T	A	7: 29,828,563	F224L	probably benign	Het

Other mutations in Lig4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
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
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
R9672:Lig4	UTSW	8	9973213	missense	probably damaging	0.98

Posted On

2011-12-09