Incidental Mutation 'R0576:Tlr4'
ID 56222
Institutional Source Beutler Lab
Gene Symbol Tlr4
Ensembl Gene ENSMUSG00000039005
Gene Name toll-like receptor 4
Synonyms Lps, lipopolysaccharide response, Rasl2-8
MMRRC Submission 038766-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0576 (G1)
Quality Score 225
Status Validated
Chromosome 4
Chromosomal Location 66745788-66765338 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 66757732 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Serine at position 175 (N175S)
Ref Sequence ENSEMBL: ENSMUSP00000045770 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000048096] [ENSMUST00000107365]
AlphaFold Q9QUK6
PDB Structure Crystal structure of mouse TLR4 and mouse MD-2 complex [X-RAY DIFFRACTION]
Crystal structure of mouse TLR4/MD-2/lipid IVa complex [X-RAY DIFFRACTION]
Crystal structure of mouse TLR4/MD-2/LPS complex [X-RAY DIFFRACTION]
Predicted Effect probably benign
Transcript: ENSMUST00000048096
AA Change: N175S

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000045770
Gene: ENSMUSG00000039005
AA Change: N175S

DomainStartEndE-ValueType
LRR 76 99 7.36e0 SMART
LRR 100 123 1.86e0 SMART
LRR 173 196 8.24e0 SMART
LRR 370 401 4.33e1 SMART
LRR 468 492 2.54e2 SMART
LRR 493 516 1.86e2 SMART
LRR 517 540 1.67e2 SMART
LRR 541 563 1.92e2 SMART
LRRCT 576 626 4.74e-3 SMART
transmembrane domain 636 658 N/A INTRINSIC
TIR 671 816 7.3e-39 SMART
low complexity region 822 833 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000107365
SMART Domains Protein: ENSMUSP00000102988
Gene: ENSMUSG00000039005

DomainStartEndE-ValueType
PDB:3VQ2|B 22 86 2e-38 PDB
SCOP:d1m0za_ 27 86 4e-6 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000143580
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147008
Meta Mutation Damage Score 0.0607 question?
Coding Region Coverage
  • 1x: 99.7%
  • 3x: 99.1%
  • 10x: 97.6%
  • 20x: 94.9%
Validation Efficiency 92% (47/51)
MGI Phenotype FUNCTION: This gene belongs to the evolutionarily-conserved Toll-like receptor family, whose members are type-1 transmembrane proteins that are involved in innate immunity. Toll-like receptors are characterized by an extracellular leucine-rich repeat domain that functions in ligand recognition and an intracellular toll/interleukin-1 receptor-like domain that is crucial for signal transduction. The receptor encoded by this gene mediates the innate immune response to bacterial lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria, through synthesis of pro-inflammatory cytokines and chemokines. In addition, this protein can recognize other pathogens from Gram-negative and Gram-positive bacteria as well as viral components. Mice deficient in this gene display a number of immune response-related phenotypes including hyporesponsiveness to bacterial lipopolysaccharide and increased levels of respiratory syncytial virus compared to controls. [provided by RefSeq, Sep 2015]
PHENOTYPE: Homozygotes for spontaneous or targeted mutations are hyporesponsive to bacterial lipopolysaccharide and more susceptible to infection by gram negative bacteria. [provided by MGI curators]
Allele List at MGI

All alleles(10) : Targeted(2) Spontaneous(6) Chemically induced(2)

Other mutations in this stock
Total: 47 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Ccdc77 T A 6: 120,308,809 (GRCm39) L335F probably benign Het
Ccr3 T A 9: 123,829,046 (GRCm39) F127Y probably damaging Het
Cfap43 T C 19: 47,785,579 (GRCm39) N437S probably benign Het
Cfh A G 1: 140,064,553 (GRCm39) V365A probably damaging Het
Copg1 T A 6: 87,874,945 (GRCm39) V380D probably damaging Het
Cxxc1 T C 18: 74,353,256 (GRCm39) I497T possibly damaging Het
Disp3 G A 4: 148,326,047 (GRCm39) T1237I possibly damaging Het
Dnaaf9 A T 2: 130,555,390 (GRCm39) F839L probably benign Het
Dnah7a A T 1: 53,675,246 (GRCm39) F360L probably benign Het
Dnhd1 C T 7: 105,363,252 (GRCm39) A3938V probably damaging Het
Eif4g1 A G 16: 20,502,818 (GRCm39) D1000G probably damaging Het
Emsy A T 7: 98,242,983 (GRCm39) V1052D probably damaging Het
Ep400 A G 5: 110,858,959 (GRCm39) probably benign Het
Fa2h T C 8: 112,082,779 (GRCm39) H146R probably damaging Het
Gad1 G A 2: 70,424,996 (GRCm39) C430Y probably benign Het
Gtse1 T C 15: 85,753,252 (GRCm39) S456P probably damaging Het
Gucy2g T C 19: 55,187,202 (GRCm39) T1073A probably damaging Het
Hectd2 T G 19: 36,562,897 (GRCm39) N3K probably benign Het
Hmcn1 A T 1: 150,525,768 (GRCm39) C3318* probably null Het
Lipo2 C T 19: 33,726,824 (GRCm39) S71N probably benign Het
Mynn G T 3: 30,661,217 (GRCm39) D100Y probably damaging Het
Myo16 G A 8: 10,612,318 (GRCm39) probably null Het
Npr2 G T 4: 43,640,947 (GRCm39) K384N probably benign Het
Nrde2 A G 12: 100,098,492 (GRCm39) V725A possibly damaging Het
Or11h23 T A 14: 50,948,661 (GRCm39) S291R probably damaging Het
Or2l13 A G 16: 19,305,938 (GRCm39) M117V probably damaging Het
Otud7a C T 7: 63,335,266 (GRCm39) P101S possibly damaging Het
Pcdhb7 T A 18: 37,475,410 (GRCm39) L182Q probably benign Het
Pdss1 A G 2: 22,805,425 (GRCm39) probably null Het
Ppargc1b T A 18: 61,444,512 (GRCm39) H233L probably damaging Het
Ppm1b A G 17: 85,320,987 (GRCm39) probably null Het
Prdm14 A T 1: 13,195,949 (GRCm39) S37R possibly damaging Het
Prss45 A G 9: 110,667,497 (GRCm39) T39A probably benign Het
Qars1 T C 9: 108,392,161 (GRCm39) probably benign Het
Rxfp2 T G 5: 149,961,712 (GRCm39) H77Q probably benign Het
Scd4 A G 19: 44,329,685 (GRCm39) M219V probably benign Het
Sec24b G T 3: 129,834,985 (GRCm39) P71Q probably benign Het
Snd1 T G 6: 28,886,576 (GRCm39) V861G probably benign Het
Sspo A G 6: 48,441,876 (GRCm39) probably null Het
Tas2r129 A G 6: 132,928,497 (GRCm39) T145A probably benign Het
Tbc1d31 T A 15: 57,833,120 (GRCm39) I953N possibly damaging Het
Tspyl4 A G 10: 34,174,518 (GRCm39) N337D probably damaging Het
Ttn A T 2: 76,642,545 (GRCm39) L13330H probably damaging Het
Usp33 T A 3: 152,089,756 (GRCm39) Y765* probably null Het
Vmn2r59 T A 7: 41,696,529 (GRCm39) Y71F probably benign Het
Zbed6 A G 1: 133,585,576 (GRCm39) F587S probably benign Het
Zfhx4 T C 3: 5,467,161 (GRCm39) S2465P probably damaging Het
Other mutations in Tlr4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01120:Tlr4 APN 4 66,758,662 (GRCm39) missense probably benign 0.01
IGL01343:Tlr4 APN 4 66,752,124 (GRCm39) splice site probably benign
IGL01669:Tlr4 APN 4 66,759,504 (GRCm39) missense possibly damaging 0.48
IGL01875:Tlr4 APN 4 66,757,726 (GRCm39) missense probably damaging 1.00
IGL02138:Tlr4 APN 4 66,759,202 (GRCm39) missense probably damaging 0.99
IGL02244:Tlr4 APN 4 66,752,298 (GRCm39) critical splice donor site probably null
IGL02793:Tlr4 APN 4 66,757,681 (GRCm39) missense probably damaging 1.00
IGL03269:Tlr4 APN 4 66,759,033 (GRCm39) missense probably damaging 1.00
IGL03288:Tlr4 APN 4 66,757,990 (GRCm39) missense probably damaging 0.99
bugsy UTSW 4 66,757,491 (GRCm39) nonsense probably null
Cruyff UTSW 4 66,758,563 (GRCm39) missense probably damaging 1.00
don_knotts UTSW 4 66,759,409 (GRCm39) missense probably damaging 1.00
Guardiola UTSW 4 66,757,540 (GRCm39) missense probably damaging 1.00
Lops UTSW 4 66,752,117 (GRCm39) splice site probably null
lps3 UTSW 4 66,759,334 (GRCm39) missense probably damaging 1.00
Lps4 UTSW 4 66,759,379 (GRCm39) missense probably damaging 1.00
milquetoast UTSW 4 66,757,681 (GRCm39) missense probably damaging 1.00
salvador UTSW 4 66,758,443 (GRCm39) missense probably damaging 0.99
R0449:Tlr4 UTSW 4 66,757,857 (GRCm39) missense probably damaging 0.99
R0481:Tlr4 UTSW 4 66,746,153 (GRCm39) missense probably benign 0.05
R0827:Tlr4 UTSW 4 66,752,117 (GRCm39) splice site probably null
R1488:Tlr4 UTSW 4 66,757,786 (GRCm39) missense probably damaging 1.00
R1490:Tlr4 UTSW 4 66,757,611 (GRCm39) missense possibly damaging 0.56
R1522:Tlr4 UTSW 4 66,757,933 (GRCm39) missense possibly damaging 0.80
R1616:Tlr4 UTSW 4 66,757,717 (GRCm39) missense probably damaging 1.00
R1681:Tlr4 UTSW 4 66,759,342 (GRCm39) missense probably damaging 1.00
R1738:Tlr4 UTSW 4 66,759,313 (GRCm39) missense probably benign 0.19
R1888:Tlr4 UTSW 4 66,759,409 (GRCm39) missense probably damaging 1.00
R1888:Tlr4 UTSW 4 66,759,409 (GRCm39) missense probably damaging 1.00
R1929:Tlr4 UTSW 4 66,757,681 (GRCm39) missense probably damaging 1.00
R1982:Tlr4 UTSW 4 66,759,272 (GRCm39) missense probably benign 0.40
R1998:Tlr4 UTSW 4 66,758,707 (GRCm39) missense probably damaging 1.00
R2186:Tlr4 UTSW 4 66,758,220 (GRCm39) missense possibly damaging 0.63
R2305:Tlr4 UTSW 4 66,758,338 (GRCm39) missense probably damaging 1.00
R3011:Tlr4 UTSW 4 66,757,491 (GRCm39) nonsense probably null
R3420:Tlr4 UTSW 4 66,757,773 (GRCm39) missense probably benign 0.37
R3422:Tlr4 UTSW 4 66,757,773 (GRCm39) missense probably benign 0.37
R3818:Tlr4 UTSW 4 66,759,553 (GRCm39) missense probably benign 0.00
R4212:Tlr4 UTSW 4 66,758,563 (GRCm39) missense probably damaging 1.00
R4213:Tlr4 UTSW 4 66,758,563 (GRCm39) missense probably damaging 1.00
R4417:Tlr4 UTSW 4 66,757,540 (GRCm39) missense probably damaging 1.00
R4630:Tlr4 UTSW 4 66,757,477 (GRCm39) missense probably benign 0.44
R4735:Tlr4 UTSW 4 66,759,435 (GRCm39) missense probably damaging 1.00
R5191:Tlr4 UTSW 4 66,759,616 (GRCm39) missense probably damaging 0.96
R5613:Tlr4 UTSW 4 66,759,122 (GRCm39) missense possibly damaging 0.94
R5705:Tlr4 UTSW 4 66,752,217 (GRCm39) missense probably damaging 1.00
R5726:Tlr4 UTSW 4 66,758,652 (GRCm39) missense probably benign
R6021:Tlr4 UTSW 4 66,759,103 (GRCm39) missense probably damaging 1.00
R6159:Tlr4 UTSW 4 66,758,070 (GRCm39) missense possibly damaging 0.92
R6227:Tlr4 UTSW 4 66,758,832 (GRCm39) missense probably benign
R7139:Tlr4 UTSW 4 66,758,520 (GRCm39) missense probably benign 0.06
R7199:Tlr4 UTSW 4 66,759,430 (GRCm39) missense probably damaging 0.99
R7220:Tlr4 UTSW 4 66,758,188 (GRCm39) missense probably benign
R7337:Tlr4 UTSW 4 66,758,191 (GRCm39) missense possibly damaging 0.86
R7487:Tlr4 UTSW 4 66,842,659 (GRCm39) missense probably benign 0.00
R7638:Tlr4 UTSW 4 66,758,443 (GRCm39) missense probably damaging 0.99
R7773:Tlr4 UTSW 4 66,757,836 (GRCm39) missense probably damaging 1.00
R7814:Tlr4 UTSW 4 66,759,316 (GRCm39) missense probably damaging 1.00
R7897:Tlr4 UTSW 4 66,758,058 (GRCm39) missense probably benign 0.07
R8044:Tlr4 UTSW 4 66,746,084 (GRCm39) missense probably benign 0.01
R8062:Tlr4 UTSW 4 66,758,087 (GRCm39) missense probably benign 0.00
R8080:Tlr4 UTSW 4 66,757,713 (GRCm39) missense probably damaging 1.00
R8446:Tlr4 UTSW 4 66,757,673 (GRCm39) missense probably damaging 0.98
R8916:Tlr4 UTSW 4 66,847,268 (GRCm39) missense probably benign 0.06
R9100:Tlr4 UTSW 4 66,758,518 (GRCm39) missense probably benign 0.08
R9415:Tlr4 UTSW 4 66,746,160 (GRCm39) critical splice donor site probably null
R9562:Tlr4 UTSW 4 66,759,522 (GRCm39) missense possibly damaging 0.80
R9565:Tlr4 UTSW 4 66,759,522 (GRCm39) missense possibly damaging 0.80
R9752:Tlr4 UTSW 4 66,757,912 (GRCm39) missense probably benign 0.02
X0064:Tlr4 UTSW 4 66,758,377 (GRCm39) missense probably damaging 0.99
Z1088:Tlr4 UTSW 4 66,847,319 (GRCm39) missense probably benign 0.01
Predicted Primers PCR Primer
(F):5'- ATGGCATGGCTTACACCACCTCTC -3'
(R):5'- TCAACCGATGGACGTGTAAACCAG -3'

Sequencing Primer
(F):5'- ATCCAGAGTTTTTCCCCAGG -3'
(R):5'- CGTGTAAACCAGCCAGGTTTTG -3'
Posted On 2013-07-11