Mutagenetix > Incidental Mutation

Incidental Mutation 'R4213:Tlr4'

319295

Institutional Source

Beutler Lab

Gene Symbol

Tlr4

Ensembl Gene

ENSMUSG00000039005

Gene Name

toll-like receptor 4

Synonyms

Lps, lipopolysaccharide response, Rasl2-8

MMRRC Submission

041040-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4213 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

66745788-66765338 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 66758563 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 452 (I452N)

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 damaging
Transcript: ENSMUST00000048096
AA Change: I452N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000045770
Gene: ENSMUSG00000039005
AA Change: I452N

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

Meta Mutation Damage Score

0.9014

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.6%

Validation Efficiency

97% (38/39)

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
Ankrd11	A	C	8: 123,617,765 (GRCm39)	V2029G	probably benign	Het
Arhgap28	A	T	17: 68,178,988 (GRCm39)	V291E	probably benign	Het
Cad	G	A	5: 31,229,688 (GRCm39)	V1390I	probably benign	Het
Cadps2	A	T	6: 23,599,462 (GRCm39)	D281E	probably damaging	Het
Celsr1	G	A	15: 85,916,008 (GRCm39)	T655I	probably damaging	Het
Cep350	C	G	1: 155,811,707 (GRCm39)	G411A	probably damaging	Het
Chml	A	T	1: 175,514,261 (GRCm39)	F210L	probably damaging	Het
Col4a4	A	T	1: 82,430,865 (GRCm39)	M1679K	unknown	Het
Ct45a	C	T	X: 55,590,568 (GRCm39)	V78I	probably benign	Het
Depdc1b	T	G	13: 108,525,225 (GRCm39)	F527V	probably damaging	Het
Dipk1b	C	T	2: 26,525,960 (GRCm39)	T298I	probably benign	Het
Dsg2	T	C	18: 20,731,571 (GRCm39)	L731P	probably benign	Het
Fbxo25	A	G	8: 13,989,581 (GRCm39)	T343A	probably damaging	Het
Gk5	T	C	9: 96,011,106 (GRCm39)	L72P	probably damaging	Het
Gpr137c	G	A	14: 45,483,965 (GRCm39)	E231K	probably damaging	Het
Hdc	C	T	2: 126,439,786 (GRCm39)		probably null	Het
Hydin	A	G	8: 111,183,139 (GRCm39)	N1112S	possibly damaging	Het
Itgae	A	G	11: 73,010,178 (GRCm39)	H556R	probably benign	Het
Kcnh8	GAGACCAACGAGCAGCTGATGCTTCAGA	GAGA	17: 53,032,934 (GRCm39)	74	probably benign	Het
Kplce	G	A	3: 92,776,434 (GRCm39)	P83L	probably benign	Het
Krtap17-1	A	G	11: 99,884,740 (GRCm39)	L9P	unknown	Het
Nmur1	T	G	1: 86,315,506 (GRCm39)	T87P	probably damaging	Het
Or5d16	T	C	2: 87,773,465 (GRCm39)	Y169C	probably benign	Het
Pira13	C	A	7: 3,824,553 (GRCm39)	A510S	probably damaging	Het
Ppp2r5e	A	G	12: 75,516,325 (GRCm39)	I244T	probably damaging	Het
Robo3	C	T	9: 37,333,194 (GRCm39)	G781D	probably damaging	Het
Siglec1	C	T	2: 130,916,038 (GRCm39)	E1275K	probably damaging	Het
Slc2a12	A	T	10: 22,577,993 (GRCm39)	K596N	probably benign	Het
Sorcs1	G	A	19: 50,213,613 (GRCm39)	R705C	probably damaging	Het
Sqor	G	T	2: 122,629,418 (GRCm39)	G92V	probably damaging	Het
Tob1	A	G	11: 94,105,018 (GRCm39)	T185A	probably damaging	Het
Yjefn3	G	T	8: 70,343,540 (GRCm39)	H50Q	probably benign	Het
Zswim1	T	C	2: 164,667,705 (GRCm39)	V319A	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
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'- GTAGAAATGCACTGAGCTTTAGTGG -3'
(R):5'- CCCCAAGATATTTGTTCCAATTGAC -3'

Sequencing Primer
(F):5'- GCTGTTCTTATTCTGATTTGGGAAC -3'
(R):5'- CCAATTGACATTTAGAAAGATCCAGG -3'

Posted On

2015-06-10