Incidental Mutation 'R0594:Tirap'
ID 56131
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 038784-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.182) question?
Stock # R0594 (G1)
Quality Score 225
Status Validated
Chromosome 9
Chromosomal Location 35095847-35111587 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 35100057 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glycine to Aspartic acid at position 209 (G209D)
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 damaging
Transcript: ENSMUST00000175765
AA Change: G209D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135435
Gene: ENSMUSG00000032041
AA Change: G209D

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000176021
AA Change: G209D

PolyPhen 2 Score 0.653 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000135738
Gene: ENSMUSG00000032041
AA Change: G209D

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000176531
AA Change: G209D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135224
Gene: ENSMUSG00000032041
AA Change: G209D

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
low complexity region 10 22 N/A INTRINSIC
low complexity region 65 107 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000176685
AA Change: G209D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135876
Gene: ENSMUSG00000032041
AA Change: G209D

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000177129
AA Change: G209D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135462
Gene: ENSMUSG00000032041
AA Change: G209D

DomainStartEndE-ValueType
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 0.1167 question?
Coding Region Coverage
  • 1x: 99.4%
  • 3x: 98.9%
  • 10x: 97.4%
  • 20x: 94.6%
Validation Efficiency 99% (119/120)
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: 116 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc1 T C 16: 14,207,744 (GRCm39) V41A probably benign Het
Acad11 A G 9: 103,972,762 (GRCm39) Q367R probably benign Het
Ackr4 A G 9: 103,976,203 (GRCm39) V248A possibly damaging Het
Adamts14 T C 10: 61,038,666 (GRCm39) E945G probably damaging Het
Ano2 A G 6: 125,959,728 (GRCm39) M663V probably damaging Het
Apc2 T A 10: 80,142,090 (GRCm39) C336* probably null Het
Arhgap17 A G 7: 122,893,741 (GRCm39) S560P probably benign Het
Arl5a T C 2: 52,295,026 (GRCm39) D128G probably damaging Het
Atp6v0a2 C A 5: 124,795,046 (GRCm39) R678S probably benign Het
B4galnt2 C A 11: 95,782,735 (GRCm39) A26S probably benign Het
C1qtnf1 A T 11: 118,337,454 (GRCm39) T95S possibly damaging Het
Ccdc188 T A 16: 18,036,784 (GRCm39) F241L probably benign Het
Cdh19 A T 1: 110,853,597 (GRCm39) D281E probably benign Het
Cdk5rap2 T C 4: 70,273,050 (GRCm39) E241G probably damaging Het
Cherp A T 8: 73,216,246 (GRCm39) probably null Het
Cpne9 T A 6: 113,267,361 (GRCm39) probably benign Het
Cthrc1 A T 15: 38,940,537 (GRCm39) R47W possibly damaging Het
Dcaf13 A G 15: 38,986,663 (GRCm39) E145G probably benign Het
Dcaf4 T A 12: 83,584,817 (GRCm39) probably null Het
Dgka A C 10: 128,568,979 (GRCm39) probably benign Het
Dhrs13 T A 11: 77,925,351 (GRCm39) F157L probably damaging Het
Dnajb5 A T 4: 42,956,577 (GRCm39) Y88F probably damaging Het
Dpp8 A G 9: 64,944,280 (GRCm39) T16A probably damaging Het
Dscc1 A T 15: 54,952,448 (GRCm39) I91K possibly damaging Het
Efemp2 T A 19: 5,525,091 (GRCm39) probably benign Het
Elf2 T C 3: 51,163,874 (GRCm39) T504A possibly damaging Het
Elk3 G A 10: 93,101,022 (GRCm39) S243F probably damaging Het
Ell2 A G 13: 75,898,112 (GRCm39) D93G probably damaging Het
Eln G T 5: 134,741,252 (GRCm39) probably benign Het
Eme1 C T 11: 94,541,256 (GRCm39) D189N possibly damaging Het
Epb41l2 A G 10: 25,319,668 (GRCm39) E167G possibly damaging Het
Exoc5 A T 14: 49,273,544 (GRCm39) probably benign Het
Fam170b A G 14: 32,558,271 (GRCm39) K369E unknown Het
Fam187b T A 7: 30,676,579 (GRCm39) C29* probably null Het
Fam20c T C 5: 138,752,392 (GRCm39) S260P possibly damaging Het
Fam216b G A 14: 78,324,114 (GRCm39) A21V possibly damaging Het
Fam98a A T 17: 75,845,482 (GRCm39) Y421* probably null Het
Farp2 T C 1: 93,504,222 (GRCm39) V333A probably damaging Het
Fcgr1 T C 3: 96,199,628 (GRCm39) Y93C probably damaging Het
Fgd2 A T 17: 29,584,526 (GRCm39) I157F probably damaging Het
Frmd4b T A 6: 97,302,387 (GRCm39) probably benign Het
Fut9 T C 4: 25,620,526 (GRCm39) D96G possibly damaging Het
Glt8d1 G A 14: 30,732,367 (GRCm39) probably null Het
Gm7579 T A 7: 141,766,121 (GRCm39) C176S unknown Het
Gmpr2 A G 14: 55,915,445 (GRCm39) E272G probably damaging Het
Grin2b T C 6: 135,710,927 (GRCm39) H873R probably damaging Het
Gtf2i C T 5: 134,271,027 (GRCm39) probably benign Het
Htr3b A T 9: 48,858,931 (GRCm39) V69E probably benign Het
Icam5 A G 9: 20,946,894 (GRCm39) N474S probably benign Het
Itgal T A 7: 126,913,232 (GRCm39) S610T probably damaging Het
Jag1 T A 2: 136,929,000 (GRCm39) I819L probably damaging Het
Kif9 A T 9: 110,340,408 (GRCm39) E467V probably benign Het
Krit1 T C 5: 3,873,694 (GRCm39) L491P possibly damaging Het
Lipo2 T G 19: 33,724,302 (GRCm39) I155L possibly damaging Het
Lmbr1 A G 5: 29,497,207 (GRCm39) F65L possibly damaging Het
Lsp1 G A 7: 142,042,687 (GRCm39) probably benign Het
Mgat5 T A 1: 127,339,985 (GRCm39) D455E probably damaging Het
Mical2 A T 7: 111,917,657 (GRCm39) Y338F probably damaging Het
Mre11a T G 9: 14,726,505 (GRCm39) S396A probably benign Het
Mrtfa G A 15: 80,901,375 (GRCm39) T372I probably damaging Het
Mtarc2 T C 1: 184,573,536 (GRCm39) N121D probably benign Het
Myo3a C T 2: 22,436,370 (GRCm39) probably benign Het
Naca T C 10: 127,876,224 (GRCm39) probably benign Het
Nav1 A T 1: 135,395,381 (GRCm39) I996K possibly damaging Het
Ncbp1 A G 4: 46,170,551 (GRCm39) N742S probably benign Het
Ndufaf3 G A 9: 108,444,122 (GRCm39) A2V probably benign Het
Niban3 C A 8: 72,051,779 (GRCm39) A38E probably benign Het
Ntn5 G T 7: 45,336,105 (GRCm39) A47S probably damaging Het
Or10ag57 T A 2: 87,218,298 (GRCm39) I83N probably damaging Het
Or1e25 G A 11: 73,494,218 (GRCm39) E271K probably benign Het
Or1e32 T C 11: 73,705,443 (GRCm39) H155R probably benign Het
Or2a7 T A 6: 43,151,541 (GRCm39) V207E possibly damaging Het
Or6c207 T C 10: 129,105,021 (GRCm39) Y57C possibly damaging Het
Or9i1 G T 19: 13,839,643 (GRCm39) C162F probably benign Het
Otud7a T A 7: 63,377,220 (GRCm39) L203* probably null Het
Pakap A G 4: 57,856,752 (GRCm39) T694A probably benign Het
Pcdhb13 A G 18: 37,576,984 (GRCm39) Y454C probably damaging Het
Pdzph1 C T 17: 59,261,474 (GRCm39) V853M possibly damaging Het
Plec A G 15: 76,056,453 (GRCm39) S4517P probably damaging Het
Pm20d2 C T 4: 33,181,746 (GRCm39) E286K probably damaging Het
Polr2i T A 7: 29,932,170 (GRCm39) probably null Het
Ppp1r12b A G 1: 134,704,217 (GRCm39) L879P probably damaging Het
Prf1 C A 10: 61,139,501 (GRCm39) Y486* probably null Het
Qsox2 T G 2: 26,104,056 (GRCm39) T325P probably damaging Het
Rab1b G T 19: 5,150,684 (GRCm39) probably benign Het
Rbm19 T C 5: 120,266,381 (GRCm39) probably null Het
Rhobtb2 A G 14: 70,031,397 (GRCm39) V576A probably benign Het
Rnps1 G A 17: 24,643,411 (GRCm39) V215M probably damaging Het
Rps11 A G 7: 44,773,706 (GRCm39) probably benign Het
Serpinb3d C T 1: 107,007,077 (GRCm39) M210I probably damaging Het
Sgsm1 T C 5: 113,458,428 (GRCm39) T17A probably benign Het
Slc6a3 A G 13: 73,686,761 (GRCm39) T43A probably damaging Het
Sox4 C G 13: 29,136,887 (GRCm39) A40P probably damaging Het
Spry2 A T 14: 106,130,744 (GRCm39) D147E possibly damaging Het
Stpg1 A G 4: 135,246,742 (GRCm39) N157D possibly damaging Het
Sumf1 T C 6: 108,150,375 (GRCm39) D152G probably benign Het
Tbr1 T C 2: 61,641,964 (GRCm39) S410P possibly damaging Het
Tdrd6 A G 17: 43,940,274 (GRCm39) V258A probably damaging Het
Tnfrsf8 A T 4: 145,023,431 (GRCm39) V134D probably damaging Het
Tnr A G 1: 159,677,905 (GRCm39) T97A probably benign Het
Tspan32 T A 7: 142,569,347 (GRCm39) F135L probably damaging Het
Ttn T C 2: 76,619,400 (GRCm39) K16021E probably damaging Het
Tusc3 T A 8: 39,564,122 (GRCm39) I251N probably damaging Het
Usp38 A T 8: 81,731,995 (GRCm39) I305N probably damaging Het
Usp4 T A 9: 108,248,080 (GRCm39) probably null Het
Usp5 A T 6: 124,794,387 (GRCm39) D764E probably damaging Het
Vangl2 A T 1: 171,832,224 (GRCm39) V544E probably damaging Het
Vldlr G A 19: 27,212,219 (GRCm39) V78M probably damaging Het
Vmn1r29 T C 6: 58,284,757 (GRCm39) V159A probably benign Het
Vmn2r16 T A 5: 109,511,762 (GRCm39) F656L probably damaging Het
Wdfy3 T A 5: 102,054,051 (GRCm39) I1590F possibly damaging Het
Xpo1 T A 11: 23,230,402 (GRCm39) V263E probably damaging Het
Zbtb38 A G 9: 96,568,007 (GRCm39) S1026P probably damaging Het
Zfp407 A T 18: 84,580,692 (GRCm39) D140E possibly damaging Het
Zfp637 T A 6: 117,822,647 (GRCm39) Y258* probably null Het
Zfp951 T A 5: 104,962,438 (GRCm39) Q376L possibly damaging Het
Other mutations in Tirap
AlleleSourceChrCoordTypePredicted EffectPPH 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
R1490:Tirap UTSW 9 35,100,362 (GRCm39) small deletion probably benign
R1833:Tirap UTSW 9 35,099,999 (GRCm39) missense probably benign 0.19
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'- TCTTATCTAGACACTGGATGCCTCCTG -3'
(R):5'- TGGTTCACAGACAGCCACACAG -3'

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