Incidental Mutation 'R2243:Lig4'
| ID |
240731 |
| 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 |
040243-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R2243 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
8 |
| Chromosomal Location |
10020020-10027680 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 10022161 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Cysteine to Arginine
at position 540
(C540R)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000130807
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000095476]
[ENSMUST00000170033]
|
| AlphaFold |
Q8BTF7 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000095476
AA Change: C540R
PolyPhen 2
Score 0.814 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000093130
Gene: ENSMUSG00000049717
AA Change: C540R
| 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 |
possibly damaging
Transcript: ENSMUST00000170033
AA Change: C540R
PolyPhen 2
Score 0.814 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000130807
Gene: ENSMUSG00000049717
AA Change: C540R
| 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 |
|
| Meta Mutation Damage Score |
0.1863 |
| Coding Region Coverage |
- 1x: 99.1%
- 3x: 98.5%
- 10x: 97.1%
- 20x: 94.5%
|
| Validation Efficiency |
100% (40/40) |
| 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: 36 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aadacl4fm5 |
G |
A |
4: 144,503,991 (GRCm39) |
R387C |
probably benign |
Het |
| Agbl1 |
A |
T |
7: 76,068,470 (GRCm39) |
E93D |
possibly damaging |
Het |
| Akap10 |
C |
A |
11: 61,806,327 (GRCm39) |
V134F |
possibly damaging |
Het |
| Bnc1 |
T |
C |
7: 81,623,821 (GRCm39) |
I469V |
possibly damaging |
Het |
| Bod1l |
T |
A |
5: 41,978,888 (GRCm39) |
I809L |
possibly damaging |
Het |
| Dicer1 |
T |
A |
12: 104,696,447 (GRCm39) |
E118V |
probably damaging |
Het |
| Dmbt1 |
T |
C |
7: 130,648,292 (GRCm39) |
F274S |
probably benign |
Het |
| Dnaaf2 |
T |
G |
12: 69,243,418 (GRCm39) |
T548P |
possibly damaging |
Het |
| Dysf |
G |
A |
6: 84,163,491 (GRCm39) |
|
probably null |
Het |
| Fchsd2 |
A |
G |
7: 100,883,092 (GRCm39) |
N240S |
probably benign |
Het |
| Foxb1 |
T |
C |
9: 69,667,146 (GRCm39) |
Y128C |
probably damaging |
Het |
| Fxr2 |
A |
T |
11: 69,532,896 (GRCm39) |
K158M |
possibly damaging |
Het |
| Golga4 |
C |
A |
9: 118,385,972 (GRCm39) |
D1031E |
probably benign |
Het |
| Hbb-bs |
T |
C |
7: 103,477,018 (GRCm39) |
D22G |
possibly damaging |
Het |
| Hivep2 |
C |
A |
10: 14,004,713 (GRCm39) |
T437K |
probably benign |
Het |
| Hnrnpul2 |
T |
A |
19: 8,798,001 (GRCm39) |
M119K |
probably benign |
Het |
| Kif18a |
C |
A |
2: 109,128,452 (GRCm39) |
H369Q |
probably damaging |
Het |
| Klhdc10 |
A |
G |
6: 30,449,558 (GRCm39) |
T207A |
probably damaging |
Het |
| Lilrb4b |
A |
T |
10: 51,357,704 (GRCm39) |
N133Y |
possibly damaging |
Het |
| Lrrc31 |
T |
A |
3: 30,739,179 (GRCm39) |
|
probably benign |
Het |
| Mslnl |
G |
A |
17: 25,961,908 (GRCm39) |
V128M |
probably damaging |
Het |
| Myof |
C |
T |
19: 37,889,767 (GRCm39) |
R2009H |
probably damaging |
Het |
| Nlrp2 |
C |
T |
7: 5,338,597 (GRCm39) |
V99I |
probably benign |
Het |
| Or2w3b |
G |
A |
11: 58,623,271 (GRCm39) |
T240M |
probably damaging |
Het |
| Pcnx1 |
T |
C |
12: 81,965,479 (GRCm39) |
S549P |
probably damaging |
Het |
| Pkhd1l1 |
T |
C |
15: 44,410,323 (GRCm39) |
F2610S |
probably damaging |
Het |
| S100a14 |
A |
G |
3: 90,435,114 (GRCm39) |
T42A |
possibly damaging |
Het |
| Serpina6 |
T |
A |
12: 103,613,187 (GRCm39) |
Y371F |
probably benign |
Het |
| Slc43a3 |
T |
C |
2: 84,778,782 (GRCm39) |
|
probably benign |
Het |
| Taldo1 |
C |
A |
7: 140,972,217 (GRCm39) |
T28K |
probably damaging |
Het |
| Tatdn3 |
T |
C |
1: 190,785,097 (GRCm39) |
Y184C |
probably damaging |
Het |
| Tep1 |
G |
C |
14: 51,091,667 (GRCm39) |
R625G |
probably benign |
Het |
| Timm44 |
A |
T |
8: 4,317,871 (GRCm39) |
I179N |
possibly damaging |
Het |
| Uimc1 |
A |
T |
13: 55,198,552 (GRCm39) |
|
probably null |
Het |
| Vmn1r68 |
A |
T |
7: 10,262,089 (GRCm39) |
V3E |
probably damaging |
Het |
| Zer1 |
A |
T |
2: 29,991,139 (GRCm39) |
F683L |
probably damaging |
Het |
|
| Other mutations in Lig4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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'- AAGCTTCCCAGATGCTTTCC -3'
(R):5'- TCACGAGGTGGCATGATGTC -3'
Sequencing Primer
(F):5'- TGCTCCAAGTCACCCAGTG -3'
(R):5'- CATGATGTCTCACTTTTTGTGTGCAG -3'
|
| Posted On |
2014-10-15 |
Incidental Mutation