Mutagenetix > Incidental Mutation

Incidental Mutation 'R6227:Tlr4'

504390

Institutional Source

Beutler Lab

Gene Symbol

Tlr4

Ensembl Gene

ENSMUSG00000039005

Gene Name

toll-like receptor 4

Synonyms

Lps, lipopolysaccharide response, Rasl2-8

MMRRC Submission

044398-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R6227 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

66745788-66765338 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 66758832 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 542 (Y542H)

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: Y542H

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000045770
Gene: ENSMUSG00000039005
AA Change: Y542H

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.4%
20x: 95.4%

Validation Efficiency

97% (61/63)

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: 33 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921504E06Rik	T	C	2: 19,558,581 (GRCm39)		probably null	Het
Abca4	T	A	3: 121,930,743 (GRCm39)	Y205*	probably null	Het
Adgrf1	A	G	17: 43,621,164 (GRCm39)	D467G	probably benign	Het
Atp7b	T	C	8: 22,510,841 (GRCm39)	D550G	possibly damaging	Het
Bicd1	T	A	6: 149,414,674 (GRCm39)	Y462*	probably null	Het
Cfap97	T	C	8: 46,644,769 (GRCm39)		probably null	Het
Csf1r	T	A	18: 61,258,900 (GRCm39)	Y706*	probably null	Het
Dab1	C	T	4: 104,588,948 (GRCm39)	A524V	probably benign	Het
Dst	A	G	1: 34,233,621 (GRCm39)	D3443G	probably benign	Het
Fktn	C	T	4: 53,731,136 (GRCm39)	A96V	probably benign	Het
Inppl1	G	A	7: 101,473,506 (GRCm39)	T1048M	possibly damaging	Het
Itga2	T	C	13: 114,976,097 (GRCm39)	T1092A	probably benign	Het
Lactbl1	C	A	4: 136,365,229 (GRCm39)	A527E	probably benign	Het
Miga1	C	T	3: 151,984,586 (GRCm39)	A510T	probably benign	Het
Mip	T	A	10: 128,061,875 (GRCm39)	L42*	probably null	Het
Naca	T	G	10: 127,879,785 (GRCm39)		probably benign	Het
Or51f5	A	T	7: 102,423,883 (GRCm39)	I51F	probably damaging	Het
Or52l1	T	C	7: 104,829,917 (GRCm39)	Y216C	probably damaging	Het
Or6c69	T	A	10: 129,747,536 (GRCm39)	T204S	probably damaging	Het
Pcm1	T	A	8: 41,783,862 (GRCm39)	M1986K	probably damaging	Het
Pex6	T	A	17: 47,023,034 (GRCm39)	D203E	probably benign	Het
Rlbp1	T	C	7: 79,029,876 (GRCm39)	N119S	probably benign	Het
Rptn	C	G	3: 93,305,437 (GRCm39)	H923Q	possibly damaging	Het
Rusc1	T	A	3: 88,999,048 (GRCm39)	T245S	probably benign	Het
Slc26a5	A	T	5: 22,026,095 (GRCm39)	C378S	probably damaging	Het
Smtn	A	G	11: 3,477,624 (GRCm39)		probably benign	Het
Tes3-ps	T	C	13: 49,647,516 (GRCm39)	C131R	probably damaging	Het
Thbs4	T	C	13: 92,911,190 (GRCm39)	E331G	probably null	Het
Trf	G	A	9: 103,107,504 (GRCm39)		probably benign	Het
Trim75	T	A	8: 65,435,748 (GRCm39)	H234L	probably benign	Het
Zan	T	G	5: 137,466,605 (GRCm39)	R417S	probably damaging	Het
Zfp213	T	C	17: 23,776,996 (GRCm39)	T349A	probably benign	Het
Zfp709	TCGACG	TCG	8: 72,644,552 (GRCm39)		probably benign	Het

Other mutations in Tlr4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R0576:Tlr4	UTSW	4	66,757,732 (GRCm39)	missense	probably benign	0.00
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
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'- TGGCTTGACCAGTCTCAAC -3'
(R):5'- CACCAAGAACTGCTTCTGTTC -3'

Sequencing Primer
(F):5'- GGCTGGCAATTCTTTCAAAGAC -3'
(R):5'- GTTCCTTGACCCACTGCAGG -3'

Posted On

2018-02-28