Incidental Mutation 'IGL00229:Lig4'
ID 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, tiny, 5830471N16Rik
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # IGL00229
Quality Score
Status
Chromosome 8
Chromosomal Location 10020020-10027680 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 10022775 bp (GRCm39)
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca4 A G 3: 121,964,603 (GRCm39) T929A probably damaging Het
Adam6b G A 12: 113,455,013 (GRCm39) R610H probably damaging Het
Adamts12 T A 15: 11,311,685 (GRCm39) M1314K probably benign Het
Alg6 T A 4: 99,641,291 (GRCm39) F152I probably damaging Het
Aopep A G 13: 63,347,314 (GRCm39) probably benign Het
Arid5b A G 10: 67,964,805 (GRCm39) S289P probably damaging Het
Axin1 T C 17: 26,413,046 (GRCm39) F780L probably damaging Het
C9 C T 15: 6,512,712 (GRCm39) S278L possibly damaging Het
Calr4 A T 4: 109,101,312 (GRCm39) I65F probably damaging Het
Cdh23 A G 10: 60,359,327 (GRCm39) V260A probably benign Het
Ddx25 T C 9: 35,454,891 (GRCm39) probably benign Het
Dppa4 A G 16: 48,111,446 (GRCm39) T92A possibly damaging Het
Ercc5 T C 1: 44,203,058 (GRCm39) Y232H probably damaging Het
Exoc4 A G 6: 33,895,334 (GRCm39) probably null Het
Fam149a A G 8: 45,804,823 (GRCm39) V253A probably damaging Het
Fam209 C T 2: 172,316,102 (GRCm39) T159I probably damaging Het
Gcfc2 A T 6: 81,912,996 (GRCm39) N265I probably damaging Het
Glud1 T C 14: 34,058,087 (GRCm39) V366A probably benign Het
Hdac10 T C 15: 89,012,645 (GRCm39) T3A probably damaging Het
Ifnar1 T C 16: 91,286,670 (GRCm39) S54P probably damaging Het
Itpr2 T C 6: 146,045,683 (GRCm39) Y2561C probably damaging Het
Klhl30 A G 1: 91,281,879 (GRCm39) E160G possibly damaging Het
Kmt2d A T 15: 98,760,214 (GRCm39) S1015T unknown Het
Lactb2 A G 1: 13,730,598 (GRCm39) M26T probably damaging Het
Lactbl1 A T 4: 136,358,362 (GRCm39) D111V probably damaging Het
Lrrc8e T A 8: 4,285,921 (GRCm39) D715E probably benign Het
Med6 A T 12: 81,626,348 (GRCm39) V142D possibly damaging Het
Men1 G A 19: 6,387,237 (GRCm39) probably null Het
Mettl13 A G 1: 162,363,434 (GRCm39) V600A possibly damaging Het
Mpdz A T 4: 81,228,461 (GRCm39) C1314* probably null Het
Nbeal2 A G 9: 110,464,937 (GRCm39) V1009A probably damaging Het
Nmur2 A G 11: 55,931,603 (GRCm39) L36P probably damaging Het
Nudt2 T A 4: 41,480,474 (GRCm39) L119Q probably damaging Het
Or5b117 T C 19: 13,431,204 (GRCm39) M226V possibly damaging Het
Osbpl3 C T 6: 50,300,048 (GRCm39) E519K probably damaging Het
Pak6 A T 2: 118,520,326 (GRCm39) T106S possibly damaging Het
Pggt1b T G 18: 46,413,786 (GRCm39) Q34P probably benign Het
Phactr4 T C 4: 132,098,303 (GRCm39) T322A possibly damaging Het
Plekhj1 T C 10: 80,632,436 (GRCm39) probably null Het
Pnpt1 T C 11: 29,104,217 (GRCm39) probably null Het
Pramel32 A G 4: 88,547,290 (GRCm39) I214T probably damaging Het
Prr14l T C 5: 32,988,020 (GRCm39) I492V probably benign Het
Ranbp2 C A 10: 58,313,078 (GRCm39) A1266E probably damaging Het
Riok3 G A 18: 12,270,077 (GRCm39) D140N probably damaging Het
Rsph4a G A 10: 33,790,339 (GRCm39) E643K probably damaging Het
Scara3 T G 14: 66,170,570 (GRCm39) E103A probably benign Het
Sgk3 T C 1: 9,938,609 (GRCm39) V33A probably damaging Het
Slc38a4 A G 15: 96,897,375 (GRCm39) F480S probably damaging Het
Slc44a1 G A 4: 53,543,571 (GRCm39) V372M probably damaging Het
Slc9a2 A G 1: 40,806,897 (GRCm39) Y728C probably benign Het
Sox4 C A 13: 29,136,956 (GRCm39) G17W probably damaging Het
Spidr A T 16: 15,713,442 (GRCm39) L847Q probably damaging Het
Sptb A G 12: 76,667,527 (GRCm39) S857P probably benign Het
Syde1 A G 10: 78,421,643 (GRCm39) V636A probably damaging Het
Syna A G 5: 134,588,571 (GRCm39) L126P possibly damaging Het
Taar2 A G 10: 23,817,266 (GRCm39) T269A possibly damaging Het
Tapbp C T 17: 34,144,678 (GRCm39) T258I probably damaging Het
Tcf20 T A 15: 82,741,343 (GRCm39) Q36L possibly damaging Het
Tmem131l A T 3: 83,849,807 (GRCm39) M260K probably damaging Het
Tnc T A 4: 63,935,061 (GRCm39) probably benign Het
Ugp2 T A 11: 21,304,345 (GRCm39) E27D probably benign Het
Vps35l T A 7: 118,403,414 (GRCm39) probably benign Het
Wdr27 A T 17: 15,148,572 (GRCm39) C140* probably null Het
Wnt2b T C 3: 104,860,449 (GRCm39) T153A possibly damaging Het
Xirp2 A T 2: 67,343,719 (GRCm39) T1987S probably benign Het
Zfp36l1 C A 12: 80,157,238 (GRCm39) G48C probably damaging Het
Zfp474 A T 18: 52,771,565 (GRCm39) I73F possibly damaging Het
Zfp790 T A 7: 29,527,988 (GRCm39) F224L probably benign Het
Other mutations in Lig4
AlleleSourceChrCoordTypePredicted EffectPPH Score
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
R1674:Lig4 UTSW 8 10,021,692 (GRCm39) missense probably benign 0.01
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
Posted On 2011-12-09