Mutagenetix > Incidental Mutation

Incidental Mutation 'R0184:Tirap'

23975

Institutional Source

Beutler Lab

Gene Symbol

Tirap

Ensembl Gene

ENSMUSG00000032041

Gene Name

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

Synonyms

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

MMRRC Submission

038449-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.158) question?

Stock #

R0184 (G1)

Quality Score

225

Status

Validated (trace)

Chromosome

Chromosomal Location

35184551-35200291 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 35189194 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 65 (S65P)

Ref Sequence

ENSEMBL: ENSMUSP00000134984 (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: S65P

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

SMART Domains

Protein: ENSMUSP00000135435
Gene: ENSMUSG00000032041
AA Change: S65P

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
AA Change: S65P

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

SMART Domains

Protein: ENSMUSP00000135738
Gene: ENSMUSG00000032041
AA Change: S65P

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: S65P

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

SMART Domains

Protein: ENSMUSP00000135224
Gene: ENSMUSG00000032041
AA Change: S65P

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
AA Change: S65P

PolyPhen 2 Score 0.086 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000134984
Gene: ENSMUSG00000032041
AA Change: S65P

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: S65P

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

SMART Domains

Protein: ENSMUSP00000135876
Gene: ENSMUSG00000032041
AA Change: S65P

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: S65P

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

SMART Domains

Protein: ENSMUSP00000135462
Gene: ENSMUSG00000032041
AA Change: S65P

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: 99.1%
3x: 98.3%
10x: 96.6%
20x: 93.9%

Validation Efficiency

66% (50/76)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700006A11Rik	C	A	3: 124,419,250 (GRCm38)	V131F	probably damaging	Het
Adam28	T	C	14: 68,637,373 (GRCm38)	D285G	probably benign	Het
Akr1c13	A	G	13: 4,194,056 (GRCm38)	E36G	probably damaging	Het
Antxr2	A	G	5: 97,980,030 (GRCm38)	L214S	probably damaging	Het
Arhgap26	T	A	18: 38,617,673 (GRCm38)	D46E	unknown	Het
Armc9	T	C	1: 86,198,370 (GRCm38)	L61P	probably damaging	Het
Bicc1	C	A	10: 71,079,215 (GRCm38)	R73L	probably benign	Het
Calm2	T	C	17: 87,435,841 (GRCm38)	N43S	probably benign	Het
Cct7	A	G	6: 85,461,554 (GRCm38)	D105G	probably null	Het
Cdk18	T	C	1: 132,118,538 (GRCm38)	N215D	probably benign	Het
Cep126	T	C	9: 8,103,395 (GRCm38)	T205A	probably benign	Het
Cfap57	A	T	4: 118,599,012 (GRCm38)	I495N	probably damaging	Het
Cyp2b9	T	A	7: 26,187,007 (GRCm38)	C152*	probably null	Het
Dab2ip	G	A	2: 35,718,791 (GRCm38)	R579H	probably damaging	Het
Dnah8	T	C	17: 30,683,683 (GRCm38)	V905A	probably benign	Het
Eif4h	C	A	5: 134,625,375 (GRCm38)	D134Y	possibly damaging	Het
Espl1	T	A	15: 102,299,216 (GRCm38)	S372T	probably benign	Het
Fat2	T	A	11: 55,296,288 (GRCm38)	H1244L	probably damaging	Het
Fbxo11	T	A	17: 88,008,673 (GRCm38)	N443I	probably benign	Het
Git2	G	A	5: 114,739,037 (GRCm38)	T128M	possibly damaging	Het
Gm10985	T	A	3: 53,845,258 (GRCm38)	Y21N	probably damaging	Het
Gm12790	A	T	4: 101,967,614 (GRCm38)	Y152*	probably null	Het
Heatr5a	T	C	12: 51,909,969 (GRCm38)	D1115G	probably benign	Het
Hipk2	T	C	6: 38,718,931 (GRCm38)	N726S	possibly damaging	Het
Hrg	T	C	16: 22,953,771 (GRCm38)		probably null	Het
Iars	T	G	13: 49,722,212 (GRCm38)	S792A	probably benign	Het
Igf1r	A	G	7: 68,226,193 (GRCm38)	N1301S	possibly damaging	Het
Il22	A	T	10: 118,205,606 (GRCm38)	I75F	probably damaging	Het
Ilkap	T	C	1: 91,376,305 (GRCm38)		probably benign	Het
Ints13	A	T	6: 146,555,044 (GRCm38)	Y435N	probably benign	Het
Ints8	A	C	4: 11,218,637 (GRCm38)	S797A	probably benign	Het
Itgad	T	A	7: 128,189,231 (GRCm38)	D405E	probably benign	Het
Itgam	A	T	7: 128,086,058 (GRCm38)	I448F	probably damaging	Het
Klk1	C	T	7: 44,228,749 (GRCm38)	T41I	possibly damaging	Het
Mcrip1	T	C	11: 120,544,884 (GRCm38)	M1V	probably null	Het
Mdga1	A	G	17: 29,852,442 (GRCm38)	Y128H	probably damaging	Het
Mtor	G	T	4: 148,464,971 (GRCm38)	R604L	probably benign	Het
Olfr1170	A	T	2: 88,224,780 (GRCm38)	L84*	probably null	Het
Olfr656	T	C	7: 104,618,240 (GRCm38)	V187A	probably damaging	Het
Pcdhb7	T	A	18: 37,343,390 (GRCm38)	D526E	probably benign	Het
Pip4k2a	T	C	2: 18,889,128 (GRCm38)	D139G	probably damaging	Het
Pkp3	A	C	7: 141,088,367 (GRCm38)	N536T	probably benign	Het
Pla2g4c	T	A	7: 13,356,220 (GRCm38)	S524T	probably benign	Het
Pno1	T	C	11: 17,211,127 (GRCm38)	E69G	probably benign	Het
Pold1	C	T	7: 44,541,715 (GRCm38)	V231M	probably benign	Het
Poli	A	G	18: 70,522,731 (GRCm38)	S248P	probably damaging	Het
Ppox	C	T	1: 171,279,552 (GRCm38)	S138N	probably damaging	Het
Psg20	T	C	7: 18,685,976 (GRCm38)	E6G	probably null	Het
Rbmx	C	T	X: 57,391,566 (GRCm38)		probably null	Het
Rln1	T	A	19: 29,331,936 (GRCm38)	K148*	probably null	Het
Rnf213	C	T	11: 119,414,521 (GRCm38)	T526I	probably damaging	Het
Rps6kc1	A	T	1: 190,799,093 (GRCm38)	V904E	probably null	Het
Sf3b2	T	A	19: 5,283,672 (GRCm38)	I633F	probably damaging	Het
Sfswap	T	A	5: 129,507,189 (GRCm38)	I189N	probably damaging	Het
Smarca2	T	A	19: 26,692,249 (GRCm38)	Y973*	probably null	Het
Spink5	G	A	18: 44,003,198 (GRCm38)	D559N	probably benign	Het
Spty2d1	C	T	7: 46,997,574 (GRCm38)	V536I	possibly damaging	Het
Tbx3	T	C	5: 119,675,562 (GRCm38)	I221T	probably damaging	Het
Tcf20	T	A	15: 82,852,300 (GRCm38)	D1650V	probably damaging	Het
Thsd7b	A	G	1: 129,430,964 (GRCm38)	K45R	probably benign	Het
Trim25	C	T	11: 88,999,640 (GRCm38)	P51L	probably damaging	Het
Trim61	T	C	8: 65,014,417 (GRCm38)	N64S	probably benign	Het
Twf1	T	A	15: 94,581,067 (GRCm38)		probably null	Het
Ubr4	A	C	4: 139,445,262 (GRCm38)	T1692P	probably damaging	Het
Usp3	A	G	9: 66,562,581 (GRCm38)	M86T	probably damaging	Het
Utrn	T	C	10: 12,667,618 (GRCm38)	D1762G	probably benign	Het
V1rd19	T	A	7: 24,003,207 (GRCm38)	F33I	probably benign	Het
Vmn2r52	T	C	7: 10,159,338 (GRCm38)	S625G	probably damaging	Het
Vmn2r90	G	A	17: 17,726,877 (GRCm38)	W472*	probably null	Het
Vrk2	C	A	11: 26,550,046 (GRCm38)	A56S	probably damaging	Het
Yeats2	C	T	16: 20,203,685 (GRCm38)	P620S	possibly damaging	Het
Zbtb21	C	T	16: 97,950,513 (GRCm38)	D171N	probably damaging	Het
Zeb1	A	T	18: 5,766,808 (GRCm38)	I440F	probably damaging	Het
Zfp292	A	G	4: 34,819,563 (GRCm38)	I253T	probably 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	35,189,162 (GRCm38)	missense	probably benign	0.34
R0594:Tirap	UTSW	9	35,188,761 (GRCm38)	missense	probably damaging	1.00
R1490:Tirap	UTSW	9	35,189,066 (GRCm38)	small deletion	probably benign
R1833:Tirap	UTSW	9	35,188,703 (GRCm38)	missense	probably benign	0.19
R1993:Tirap	UTSW	9	35,191,016 (GRCm38)	critical splice donor site	probably null
R5703:Tirap	UTSW	9	35,188,758 (GRCm38)	missense	probably damaging	1.00
R5875:Tirap	UTSW	9	35,189,169 (GRCm38)	missense	probably damaging	0.96
R7257:Tirap	UTSW	9	35,189,034 (GRCm38)	missense	probably damaging	1.00
R7283:Tirap	UTSW	9	35,188,929 (GRCm38)	missense	probably damaging	0.98
R8369:Tirap	UTSW	9	35,188,756 (GRCm38)	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- CGCAGACATCGTAGTCTTTGCTCC -3'
(R):5'- TCGTAATTGGGCTGGTAAAACCCAC -3'

Sequencing Primer
(F):5'- AGTCTTTGCTCCAGCGGC -3'
(R):5'- CCACGGACAGGATTCAAATTG -3'

Posted On

2013-04-16