Mutagenetix > Incidental Mutation

Incidental Mutation 'R1833:Tirap'

204965

Institutional Source

Beutler Lab

Gene Symbol

Tirap

Ensembl Gene

ENSMUSG00000032041

Gene Name

toll-interleukin 1 receptor (TIR) domain-containing adaptor protein

Synonyms

Mal, wyatt, MyD88-adapter-like, Mal, C130027E04Rik

MMRRC Submission

039860-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.182) question?

Stock #

R1833 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

35095847-35111587 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 35099999 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Serine at position 228 (R228S)

Ref Sequence

ENSEMBL: ENSMUSP00000135462 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000175765] [ENSMUST00000176021] [ENSMUST00000176531] [ENSMUST00000176611] [ENSMUST00000176685] [ENSMUST00000177052] [ENSMUST00000177129]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000175765
AA Change: R228S

PolyPhen 2 Score 0.185 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000135435
Gene: ENSMUSG00000032041
AA Change: R228S

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	65	107	N/A	INTRINSIC
Pfam:TIR	113	206	2.4e-8	PFAM
Pfam:TIR_2	116	226	1.9e-14	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000176021

SMART Domains

Protein: ENSMUSP00000135738
Gene: ENSMUSG00000032041

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	65	107	N/A	INTRINSIC
Pfam:TIR	116	215	3.1e-10	PFAM
Pfam:TIR_2	116	219	6.1e-14	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000176531
AA Change: R228S

PolyPhen 2 Score 0.185 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000135224
Gene: ENSMUSG00000032041
AA Change: R228S

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	65	107	N/A	INTRINSIC
Pfam:TIR	116	225	2.6e-10	PFAM
Pfam:TIR_2	116	226	1.4e-14	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000176611

SMART Domains

Protein: ENSMUSP00000134984
Gene: ENSMUSG00000032041

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	65	107	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000176685
AA Change: R228S

PolyPhen 2 Score 0.185 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000135876
Gene: ENSMUSG00000032041
AA Change: R228S

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	65	107	N/A	INTRINSIC
Pfam:TIR	116	225	2.6e-10	PFAM
Pfam:TIR_2	116	226	1.4e-14	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000177052

Predicted Effect

probably benign
Transcript: ENSMUST00000177129
AA Change: R228S

PolyPhen 2 Score 0.185 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000135462
Gene: ENSMUSG00000032041
AA Change: R228S

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	65	107	N/A	INTRINSIC
Pfam:TIR	116	225	2.6e-10	PFAM
Pfam:TIR_2	116	226	1.4e-14	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000214606

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 97.4%
3x: 96.8%
10x: 95.1%
20x: 91.9%

Validation Efficiency

99% (83/84)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The innate immune system recognizes microbial pathogens through Toll-like receptors (TLRs), which identify pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns and all TLRs have a Toll-interleukin 1 receptor (TIR) domain, which is responsible for signal transduction. The protein encoded by this gene is a TIR adaptor protein involved in the TLR4 signaling pathway of the immune system. It activates NF-kappa-B, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mutations in this gene lead to impaired cytokine secretion in response to TLR2 and TLR4 ligands. Homozygous null mice may also show low serum IgG3 levels, a reduced response to attenuated yellow fever vaccine, high susceptibility to bacterial infection, and altered response to myocardial infarction. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700003H04Rik	T	A	3: 124,350,509 (GRCm39)	D143V	unknown	Het
4930438A08Rik	C	T	11: 58,179,214 (GRCm39)	Q183*	probably null	Het
9230009I02Rik	A	G	11: 50,982,293 (GRCm39)		noncoding transcript	Het
Abhd12	T	A	2: 150,690,338 (GRCm39)	D119V	probably damaging	Het
Adam1b	A	G	5: 121,641,000 (GRCm39)	I15T	possibly damaging	Het
Agtpbp1	A	T	13: 59,613,797 (GRCm39)		probably null	Het
Arfgef1	G	C	1: 10,275,115 (GRCm39)	I312M	probably benign	Het
Arid4a	C	T	12: 71,122,240 (GRCm39)	L874F	possibly damaging	Het
Bcas3	G	A	11: 85,474,775 (GRCm39)	V317I	probably benign	Het
Ccr1	T	A	9: 123,764,126 (GRCm39)	I135F	probably damaging	Het
Ces2h	A	G	8: 105,747,005 (GRCm39)	E547G	possibly damaging	Het
Ces3b	T	A	8: 105,812,271 (GRCm39)	D173E	probably damaging	Het
Chd3	A	G	11: 69,244,949 (GRCm39)	L1197S	probably damaging	Het
Cngb1	A	G	8: 95,968,983 (GRCm39)	L1175P	probably damaging	Het
Cyp4f17	T	C	17: 32,743,184 (GRCm39)	F286L	probably benign	Het
Dclre1a	C	T	19: 56,529,932 (GRCm39)		probably null	Het
Dennd6a	T	A	14: 26,328,109 (GRCm39)	L44H	probably damaging	Het
Dhx16	A	G	17: 36,196,511 (GRCm39)	T560A	probably benign	Het
Dusp12	T	C	1: 170,702,022 (GRCm39)	M326V	probably benign	Het
Eif3k	T	C	7: 28,670,852 (GRCm39)	I180V	probably benign	Het
Erc1	A	G	6: 119,720,390 (GRCm39)	I437T	possibly damaging	Het
Farp2	T	A	1: 93,504,086 (GRCm39)		probably benign	Het
Foxa3	A	G	7: 18,748,499 (GRCm39)	L209P	probably damaging	Het
Garin2	G	A	12: 78,762,280 (GRCm39)		probably benign	Het
Gen1	A	T	12: 11,298,352 (GRCm39)		probably benign	Het
Gm10305	A	G	4: 99,161,363 (GRCm39)	T91A	unknown	Het
Gm14412	T	C	2: 177,007,583 (GRCm39)	D104G	probably benign	Het
Gm6900	T	C	7: 10,390,515 (GRCm39)		noncoding transcript	Het
Gpx1	A	T	9: 108,216,555 (GRCm39)	Y15F	possibly damaging	Het
H2-M10.3	T	C	17: 36,678,387 (GRCm39)	Y146C	probably damaging	Het
H2-Q7	C	A	17: 35,658,675 (GRCm39)	S104R	probably benign	Het
Hephl1	T	C	9: 14,988,224 (GRCm39)	Y628C	probably damaging	Het
Hspa5	T	A	2: 34,666,065 (GRCm39)	Y636*	probably null	Het
Htt	A	G	5: 35,063,092 (GRCm39)		probably benign	Het
Idh1	T	C	1: 65,200,273 (GRCm39)	I364V	probably benign	Het
Itgae	G	T	11: 73,007,988 (GRCm39)	A423S	possibly damaging	Het
Kng2	T	C	16: 22,830,802 (GRCm39)	N169S	possibly damaging	Het
Larp4b	C	T	13: 9,201,235 (GRCm39)	T369I	possibly damaging	Het
Lcor	T	C	19: 41,573,387 (GRCm39)	I714T	probably benign	Het
Lhfpl7	A	G	5: 113,382,435 (GRCm39)		probably benign	Het
Lonrf2	G	A	1: 38,852,357 (GRCm39)	P165S	probably benign	Het
Magi2	G	T	5: 19,432,455 (GRCm39)	G57C	probably damaging	Het
Mdn1	T	A	4: 32,720,761 (GRCm39)	H2291Q	probably damaging	Het
Mgam	T	C	6: 40,631,652 (GRCm39)		probably null	Het
Micall2	A	G	5: 139,702,508 (GRCm39)	V245A	probably benign	Het
Mipep	T	G	14: 61,109,512 (GRCm39)	Y630D	probably damaging	Het
Msx2	A	T	13: 53,622,221 (GRCm39)	M263K	probably damaging	Het
Nectin2	G	T	7: 19,451,633 (GRCm39)	P467H	probably damaging	Het
Nek10	A	T	14: 14,842,789 (GRCm38)	M165L	probably benign	Het
Nlrp4b	A	T	7: 10,459,863 (GRCm39)	M455L	probably benign	Het
Oaz3	TGGAGGCAGGAGCACGGGAGGCAGGAGCACGGGAGGCAG	TGGAGGCAGGAGCACGGGAGGCAG	3: 94,343,349 (GRCm39)		probably benign	Het
Or10ad1b	T	A	15: 98,124,846 (GRCm39)	I227F	probably damaging	Het
Or4c10	T	A	2: 89,760,645 (GRCm39)	L164*	probably null	Het
Pcx	T	A	19: 4,669,132 (GRCm39)	V710E	probably damaging	Het
Pkn2	C	T	3: 142,527,408 (GRCm39)	R347Q	probably damaging	Het
Pramel51	T	C	12: 88,145,218 (GRCm39)	E44G	possibly damaging	Het
Qsox1	C	T	1: 155,666,791 (GRCm39)	G233S	probably benign	Het
Rbl1	T	A	2: 157,037,475 (GRCm39)	N224I	probably damaging	Het
Rspry1	A	G	8: 95,362,116 (GRCm39)	T132A	probably damaging	Het
Sclt1	A	G	3: 41,681,546 (GRCm39)	V91A	probably damaging	Het
Sema4f	A	T	6: 82,895,540 (GRCm39)	L331H	probably benign	Het
Sf3b3	T	A	8: 111,544,198 (GRCm39)	Q814L	probably benign	Het
Slc19a2	T	G	1: 164,089,753 (GRCm39)	Y190D	probably damaging	Het
Smarcc1	T	A	9: 109,982,879 (GRCm39)	H204Q	possibly damaging	Het
Sox6	T	C	7: 115,376,328 (GRCm39)	K135E	probably damaging	Het
Tecpr1	T	C	5: 144,145,426 (GRCm39)	Q607R	probably damaging	Het
Tgfb1i1	A	G	7: 127,848,670 (GRCm39)		probably benign	Het
Trp53bp2	T	A	1: 182,256,581 (GRCm39)	H50Q	probably damaging	Het
Try4	A	G	6: 41,280,365 (GRCm39)	H63R	probably damaging	Het
Vmn2r25	G	A	6: 123,816,643 (GRCm39)	P313S	probably benign	Het
Vps26a	A	C	10: 62,294,825 (GRCm39)	L250V	probably benign	Het
Vwf	A	G	6: 125,619,000 (GRCm39)	H1226R	probably benign	Het
Wdtc1	TCC	TC	4: 133,036,053 (GRCm39)		probably benign	Het
Zc3hav1l	A	T	6: 38,274,881 (GRCm39)		probably benign	Het
Zfp119b	T	G	17: 56,246,271 (GRCm39)	H305P	probably damaging	Het
Zfp326	C	T	5: 106,039,035 (GRCm39)	Q134*	probably null	Het
Zfp975	C	T	7: 42,311,263 (GRCm39)	R450Q	probably benign	Het
Zfyve26	A	T	12: 79,333,032 (GRCm39)	M313K	probably benign	Het
Zscan5b	T	C	7: 6,241,965 (GRCm39)	S395P	possibly damaging	Het

Other mutations in Tirap

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
torpid	UTSW	9	35,198,707 (GRCm38)	intron	probably benign
R0084:Tirap	UTSW	9	35,100,458 (GRCm39)	missense	probably benign	0.34
R0184:Tirap	UTSW	9	35,100,490 (GRCm39)	missense	probably benign	0.09
R0594:Tirap	UTSW	9	35,100,057 (GRCm39)	missense	probably damaging	1.00
R1490:Tirap	UTSW	9	35,100,362 (GRCm39)	small deletion	probably benign
R1993:Tirap	UTSW	9	35,102,312 (GRCm39)	critical splice donor site	probably null
R5703:Tirap	UTSW	9	35,100,054 (GRCm39)	missense	probably damaging	1.00
R5875:Tirap	UTSW	9	35,100,465 (GRCm39)	missense	probably damaging	0.96
R7257:Tirap	UTSW	9	35,100,330 (GRCm39)	missense	probably damaging	1.00
R7283:Tirap	UTSW	9	35,100,225 (GRCm39)	missense	probably damaging	0.98
R8369:Tirap	UTSW	9	35,100,052 (GRCm39)	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- TGTGTTCATTCTACAGTAACAGAGTCC -3'
(R):5'- TGTGCTGCTCATCACTCCAG -3'

Sequencing Primer
(F):5'- CAATGCTACTGGGTGACAATGCC -3'
(R):5'- TCCAGGCTTCCTTCGGGAC -3'

Posted On

2014-06-23