Incidental Mutation 'R1566:Lig4'
ID 175272
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 039605-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1566 (G1)
Quality Score 225
Status Not validated
Chromosome 8
Chromosomal Location 10020020-10027680 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 10023650 bp (GRCm39)
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]
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 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

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 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

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
  • 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
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700012B07Rik T A 11: 109,679,632 (GRCm39) I247F probably benign Het
Afap1l1 T C 18: 61,888,714 (GRCm39) N119S probably benign Het
Ap2a1 T C 7: 44,552,904 (GRCm39) D721G probably benign Het
Ap3m2 C T 8: 23,293,967 (GRCm39) V28M probably damaging Het
Arhgef7 A G 8: 11,832,620 (GRCm39) T32A possibly damaging Het
Avl9 C T 6: 56,713,467 (GRCm39) R242* probably null Het
Bsn G A 9: 108,003,184 (GRCm39) T407I probably benign Het
Capn3 A T 2: 120,333,474 (GRCm39) R627S possibly damaging Het
Car13 G A 3: 14,715,758 (GRCm39) R92Q probably benign Het
Clcn1 T C 6: 42,268,374 (GRCm39) I149T possibly damaging Het
Col1a2 G T 6: 4,523,613 (GRCm39) G514V probably damaging Het
Ctsw C A 19: 5,515,445 (GRCm39) C347F probably damaging Het
Dna2 C T 10: 62,784,966 (GRCm39) R28W probably benign Het
Eif1ad8 A T 12: 87,564,001 (GRCm39) H112L probably benign Het
Eml1 T A 12: 108,438,151 (GRCm39) V97D probably damaging Het
Epb41l1 A G 2: 156,363,879 (GRCm39) E796G probably benign Het
Gdnf A G 15: 7,863,895 (GRCm39) K102R probably benign Het
Gm1110 T C 9: 26,792,166 (GRCm39) E618G probably damaging Het
Gmnc T C 16: 26,782,689 (GRCm39) D22G probably damaging Het
Greb1 T C 12: 16,761,829 (GRCm39) D517G possibly damaging Het
Gsta1 A T 9: 78,149,741 (GRCm39) K185* probably null Het
Ift88 A G 14: 57,678,468 (GRCm39) D160G probably benign Het
Intu T A 3: 40,647,008 (GRCm39) I627N probably damaging Het
Itgav T A 2: 83,566,974 (GRCm39) F101L probably damaging Het
Kars1 C T 8: 112,724,290 (GRCm39) V475I probably benign Het
Klra3 G C 6: 130,310,107 (GRCm39) R138G probably benign Het
Klra7 A G 6: 130,208,564 (GRCm39) V6A probably damaging Het
Krtap6-2 A G 16: 89,216,626 (GRCm39) S114P unknown Het
Ldlrad4 T C 18: 68,383,669 (GRCm39) S122P probably benign Het
Mfsd4a T C 1: 131,986,917 (GRCm39) D137G probably damaging Het
Mmel1 C T 4: 154,968,110 (GRCm39) R149C probably damaging Het
Morc2b T A 17: 33,355,948 (GRCm39) H608L probably benign Het
Mrgpra6 G A 7: 46,838,652 (GRCm39) T182I probably benign Het
Nat8l C A 5: 34,158,200 (GRCm39) N203K probably benign Het
Nin A T 12: 70,101,253 (GRCm39) V448E probably damaging Het
Or10a4 T G 7: 106,696,759 (GRCm39) F29C probably damaging Het
Or2m12 T A 16: 19,105,077 (GRCm39) M139L possibly damaging Het
Or5k15 T A 16: 58,709,903 (GRCm39) I227F probably damaging Het
Or8k21 G A 2: 86,145,129 (GRCm39) T167I probably benign Het
Pank4 T C 4: 155,064,978 (GRCm39) L759P probably damaging Het
Pcm1 T A 8: 41,743,810 (GRCm39) N1152K probably damaging Het
Pitpnm3 A T 11: 71,949,785 (GRCm39) probably null Het
Plekhg3 T C 12: 76,618,839 (GRCm39) M497T possibly damaging Het
Ppfia3 T C 7: 44,990,112 (GRCm39) D1138G probably damaging Het
Prl6a1 T A 13: 27,499,410 (GRCm39) S59R possibly damaging Het
Pth2r A G 1: 65,427,697 (GRCm39) S457G possibly damaging Het
Rbm25 T A 12: 83,721,828 (GRCm39) N671K probably damaging Het
Rbm26 T A 14: 105,397,980 (GRCm39) K47N unknown Het
Ryr1 T A 7: 28,791,600 (GRCm39) I1435F possibly damaging Het
Scin T A 12: 40,131,673 (GRCm39) H287L probably benign Het
Serpinb9e T C 13: 33,437,477 (GRCm39) L120P probably damaging Het
Slc34a1 A C 13: 55,559,844 (GRCm39) probably null Het
Slc39a10 A G 1: 46,875,245 (GRCm39) F19S possibly damaging Het
Sos1 A G 17: 80,761,345 (GRCm39) V117A probably damaging Het
Spta1 C A 1: 174,012,272 (GRCm39) N359K probably benign Het
Sspo G A 6: 48,443,804 (GRCm39) probably null Het
Stx5a T A 19: 8,719,675 (GRCm39) D13E probably damaging Het
Supt16 G A 14: 52,414,112 (GRCm39) A489V probably damaging Het
Tap1 T A 17: 34,408,520 (GRCm39) L253Q probably benign Het
Tmc6 A G 11: 117,660,262 (GRCm39) S659P probably damaging Het
Tnfsf14 T C 17: 57,500,876 (GRCm39) D65G probably benign Het
Ttc28 G A 5: 111,373,543 (GRCm39) S962N probably damaging Het
Ugt8a T C 3: 125,669,207 (GRCm39) Y299C probably damaging Het
Upk1a A G 7: 30,309,145 (GRCm39) V59A possibly damaging Het
Usp38 T C 8: 81,711,432 (GRCm39) T868A probably benign Het
Wdsub1 G A 2: 59,707,059 (GRCm39) H58Y probably damaging Het
Zc3h7b T C 15: 81,653,035 (GRCm39) S19P possibly damaging Het
Zfp385b A C 2: 77,246,257 (GRCm39) F257V probably benign Het
Zmym4 A C 4: 126,804,940 (GRCm39) I188S possibly damaging Het
Other mutations in Lig4
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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