Incidental Mutation 'IGL01669:Lig4'
ID103418
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Lig4
Ensembl Gene ENSMUSG00000049717
Gene Nameligase IV, DNA, ATP-dependent
SynonymsDNA ligase IV, 5830471N16Rik, tiny
Accession Numbers
Is this an essential gene? Essential (E-score: 1.000) question?
Stock #IGL01669
Quality Score
Status
Chromosome8
Chromosomal Location9969049-9977686 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to C at 9973673 bp
ZygosityHeterozygous
Amino Acid Change Isoleucine to Valine at position 36 (I36V)
Ref Sequence ENSEMBL: ENSMUSP00000130807 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000048216] [ENSMUST00000095476] [ENSMUST00000139793] [ENSMUST00000170033]
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: I36V

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)
SMART Domains Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: I36V

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: I36V

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)
SMART Domains Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: I36V

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: 40 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acsl4 G T X: 142,343,188 D313E probably damaging Het
Aifm3 A C 16: 17,503,541 K453T probably benign Het
Anks1b T C 10: 90,897,238 probably benign Het
Arfgef1 T C 1: 10,159,615 D1287G probably damaging Het
Bcl3 G A 7: 19,812,491 Q140* probably null Het
Bnipl T G 3: 95,242,734 R316S probably damaging Het
Cacna1i T A 15: 80,391,757 H1916Q probably benign Het
Ccdc171 C T 4: 83,681,195 A749V probably damaging Het
Ceacam18 G A 7: 43,645,515 G333E probably damaging Het
Cul7 G T 17: 46,658,715 M969I possibly damaging Het
Cylc2 A G 4: 51,228,360 T144A probably benign Het
Cyp2c50 A T 19: 40,098,051 H294L probably damaging Het
D430041D05Rik T C 2: 104,254,961 K1081R probably damaging Het
D930020B18Rik A G 10: 121,683,961 K456R probably benign Het
Drd2 A G 9: 49,402,089 N186S possibly damaging Het
Fanci A T 7: 79,449,177 E1306D probably benign Het
Fbxl21 T A 13: 56,527,709 probably benign Het
Galk2 T A 2: 125,887,887 Y63N probably damaging Het
Git2 T C 5: 114,767,105 D97G probably damaging Het
Gm8258 T A 5: 104,776,074 noncoding transcript Het
Irf4 G T 13: 30,757,471 S270I probably damaging Het
Itgb3 C A 11: 104,633,390 probably benign Het
Itpr2 A C 6: 146,180,229 I2299R probably damaging Het
Nedd9 A G 13: 41,338,635 V133A probably damaging Het
Nup133 A C 8: 123,939,130 Y185* probably null Het
Olfr1162 T C 2: 88,049,784 Y280C possibly damaging Het
Olfr623 A T 7: 103,660,987 F88I probably benign Het
Olfr788 A G 10: 129,473,211 H173R probably damaging Het
Pgbd5 T A 8: 124,374,399 T373S possibly damaging Het
Ppp1r8 T C 4: 132,828,169 E246G probably benign Het
Rmnd5b C T 11: 51,627,900 V89M probably damaging Het
Rnf123 T C 9: 108,058,356 I969V probably damaging Het
Ror2 A G 13: 53,111,088 I656T probably damaging Het
Sgsm1 T C 5: 113,263,490 E503G probably benign Het
Smgc T A 15: 91,860,684 S381T possibly damaging Het
Tlr4 T G 4: 66,841,267 F766V possibly damaging Het
Tnc T C 4: 64,000,701 T1162A probably damaging Het
Usp39 A G 6: 72,338,493 V156A probably damaging Het
Zdhhc5 A G 2: 84,691,194 Y352H probably damaging Het
Zfp646 A G 7: 127,878,965 T105A probably benign Het
Other mutations in Lig4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00229:Lig4 APN 8 9972775 missense probably damaging 1.00
IGL00655:Lig4 APN 8 9973305 missense probably benign 0.09
IGL01388:Lig4 APN 8 9973586 missense probably damaging 1.00
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
posey UTSW 8 9972955 missense probably damaging 1.00
posey2 UTSW 8 9971585 missense probably benign
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
Posted On2014-01-21