Incidental Mutation 'R6102:Lig4'
ID 485310
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 044252-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6102 (G1)
Quality Score 225.009
Status Validated
Chromosome 8
Chromosomal Location 10020020-10027680 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 10022872 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glycine to Serine at position 303 (G303S)
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: G303S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: G303S

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: G303S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: G303S

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: 99.9%
  • 3x: 99.6%
  • 10x: 98.4%
  • 20x: 95.6%
Validation Efficiency 97% (65/67)
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: 67 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Alox12e A G 11: 70,210,849 (GRCm39) I290T possibly damaging Het
Apeh T A 9: 107,963,638 (GRCm39) D559V probably damaging Het
Aspm T A 1: 139,405,197 (GRCm39) Y1361* probably null Het
Atad5 G T 11: 80,002,398 (GRCm39) probably null Het
Ccr4 C T 9: 114,325,561 (GRCm39) probably null Het
Clasrp G A 7: 19,320,393 (GRCm39) probably benign Het
Cldn23 A G 8: 36,292,705 (GRCm39) M261T probably benign Het
Cmya5 T C 13: 93,230,739 (GRCm39) M1450V probably benign Het
Cyp4v3 T A 8: 45,773,197 (GRCm39) E202V probably damaging Het
Dnah7a A T 1: 53,598,299 (GRCm39) V1412E probably benign Het
Dnah9 A G 11: 65,881,342 (GRCm39) S2578P probably damaging Het
Dsc2 T A 18: 20,180,165 (GRCm39) Y196F probably benign Het
Exoc1 T C 5: 76,685,626 (GRCm39) S113P probably damaging Het
Fbxo6 A T 4: 148,233,979 (GRCm39) I39N probably damaging Het
Frs3 C T 17: 48,013,596 (GRCm39) H173Y probably damaging Het
Ginm1 G T 10: 7,644,260 (GRCm39) T323K probably benign Het
Golgb1 T C 16: 36,733,227 (GRCm39) S825P probably damaging Het
Hs3st3b1 A T 11: 63,812,681 (GRCm39) C11* probably null Het
Ighv3-3 G C 12: 114,160,080 (GRCm39) A110G possibly damaging Het
Igkv6-20 G A 6: 70,312,853 (GRCm39) H107Y probably benign Het
Kcnj16 A G 11: 110,916,403 (GRCm39) E355G probably benign Het
Map1b A C 13: 99,562,381 (GRCm39) V2443G unknown Het
Map3k6 T C 4: 132,974,442 (GRCm39) probably null Het
Mmp13 A G 9: 7,276,688 (GRCm39) Q261R probably benign Het
Mphosph9 T A 5: 124,435,772 (GRCm39) I554F possibly damaging Het
Mrgpra3 A T 7: 47,239,897 (GRCm39) F10I possibly damaging Het
Ms4a18 G A 19: 10,990,887 (GRCm39) T69I probably benign Het
Mtmr3 T C 11: 4,437,673 (GRCm39) N927S probably damaging Het
Necab1 T A 4: 14,989,211 (GRCm39) Q188L probably benign Het
Nfatc2 A G 2: 168,361,427 (GRCm39) probably benign Het
Or5i1 T C 2: 87,613,192 (GRCm39) F103L probably damaging Het
Or5p70 T C 7: 107,994,491 (GRCm39) S55P probably damaging Het
Or7g34 T C 9: 19,478,318 (GRCm39) M121V possibly damaging Het
Paip2b A C 6: 83,785,828 (GRCm39) V134G possibly damaging Het
Pax3 T C 1: 78,108,984 (GRCm39) T225A probably damaging Het
Pbx1 C A 1: 168,011,134 (GRCm39) A298S probably benign Het
Pcdhac2 A T 18: 37,279,335 (GRCm39) K772* probably null Het
Pcsk4 A T 10: 80,161,651 (GRCm39) Y163* probably null Het
Plcd3 A G 11: 102,971,470 (GRCm39) V58A probably damaging Het
Plek2 T A 12: 78,946,867 (GRCm39) T57S possibly damaging Het
Plscr2 C T 9: 92,169,721 (GRCm39) T57I probably benign Het
Ppp2r5b A G 19: 6,284,768 (GRCm39) S32P probably benign Het
Ppp3r2 C T 4: 49,682,022 (GRCm39) probably benign Het
Psme4 T A 11: 30,815,567 (GRCm39) L1693H probably damaging Het
Rrbp1 T A 2: 143,830,313 (GRCm39) Q618L probably damaging Het
Rsf1 ATGGCG ATGGCGACGGTGGCG 7: 97,229,111 (GRCm39) probably benign Het
Rsrc1 C T 3: 66,901,982 (GRCm39) P44L unknown Het
Serpina3b A T 12: 104,100,428 (GRCm39) T337S probably benign Het
Slc18a2 T C 19: 59,282,310 (GRCm39) Y506H probably benign Het
Slc9a9 A G 9: 94,818,482 (GRCm39) Y292C probably benign Het
Spta1 T C 1: 174,052,086 (GRCm39) V1840A probably benign Het
Ssb T C 2: 69,701,552 (GRCm39) *416Q probably null Het
Strada A G 11: 106,059,262 (GRCm39) V209A probably benign Het
Tbc1d31 A T 15: 57,799,489 (GRCm39) D225V probably damaging Het
Tgm4 T C 9: 122,885,600 (GRCm39) F381L probably benign Het
Tmem120b T A 5: 123,253,207 (GRCm39) Y203N probably damaging Het
Tmem176b A G 6: 48,812,868 (GRCm39) V109A probably benign Het
Tnfrsf11a C A 1: 105,747,671 (GRCm39) L201M possibly damaging Het
Ttn C A 2: 76,804,694 (GRCm39) probably null Het
Tubb2a T C 13: 34,259,326 (GRCm39) I155V probably benign Het
Vmn1r5 A G 6: 56,963,099 (GRCm39) D258G probably damaging Het
Vmn2r121 T C X: 123,043,272 (GRCm39) T120A probably benign Het
Vmn2r19 A T 6: 123,306,907 (GRCm39) I472F probably damaging Het
Vwa3a A G 7: 120,375,361 (GRCm39) probably null Het
Zfp273 A G 13: 67,970,466 (GRCm39) Y5C probably damaging Het
Zfp647 G A 15: 76,796,285 (GRCm39) P125L probably damaging Het
Zfp825 A G 13: 74,628,772 (GRCm39) L248P probably 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
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
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'- GAGTAACAAGTCTGTAGGCCAG -3'
(R):5'- TCTGTAGGGCTTAGTGACATCTC -3'

Sequencing Primer
(F):5'- TGTAGGCCAGAATCTTCCACC -3'
(R):5'- GTAGGGCTTAGTGACATCTCTATCAC -3'
Posted On 2017-08-16