Incidental Mutation 'R5703:Tirap'
ID 451797
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 043183-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.182) question?
Stock # R5703 (G1)
Quality Score 225
Status Not validated
Chromosome 9
Chromosomal Location 35095847-35111587 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 35100054 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Glutamine at position 210 (L210Q)
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: L210Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135435
Gene: ENSMUSG00000032041
AA Change: L210Q

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 probably damaging
Transcript: ENSMUST00000176021
AA Change: L210Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135738
Gene: ENSMUSG00000032041
AA Change: L210Q

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: L210Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135224
Gene: ENSMUSG00000032041
AA Change: L210Q

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: L210Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135876
Gene: ENSMUSG00000032041
AA Change: L210Q

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: L210Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000135462
Gene: ENSMUSG00000032041
AA Change: L210Q

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
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.1%
  • 20x: 95.0%
Validation Efficiency
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: 37 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adgrb3 T A 1: 25,459,640 (GRCm39) N605I probably damaging Het
Btd C T 14: 31,389,004 (GRCm39) R242* probably null Het
Cdc42bpg A G 19: 6,372,703 (GRCm39) D1502G possibly damaging Het
Chst2 A G 9: 95,286,985 (GRCm39) F454L probably damaging Het
Col16a1 G A 4: 129,947,092 (GRCm39) A146T probably damaging Het
Cyp3a11 A T 5: 145,797,183 (GRCm39) S399T probably benign Het
Dspp C T 5: 104,324,917 (GRCm39) H427Y possibly damaging Het
Dtx4 A T 19: 12,459,574 (GRCm39) M410K possibly damaging Het
Ecpas A T 4: 58,877,171 (GRCm39) probably null Het
Epb41l2 C T 10: 25,317,665 (GRCm39) R61W probably damaging Het
Gbp6 T C 5: 105,421,147 (GRCm39) K553E probably benign Het
Git1 CCG C 11: 77,395,494 (GRCm39) probably null Het
Gm13199 C T 2: 5,867,259 (GRCm39) probably benign Het
Gramd2a G A 9: 59,615,299 (GRCm39) G13R probably benign Het
Hoxa2 G T 6: 52,140,243 (GRCm39) Q248K probably damaging Het
Hycc1 A T 5: 24,185,577 (GRCm39) probably null Het
Krt33b T C 11: 99,916,374 (GRCm39) T228A probably benign Het
Loxhd1 A G 18: 77,444,573 (GRCm39) E324G probably damaging Het
Map3k20 A G 2: 72,232,514 (GRCm39) N390S probably benign Het
Mroh7 A G 4: 106,565,757 (GRCm39) Y126H possibly damaging Het
Muc4 G A 16: 32,555,059 (GRCm39) W15* probably null Het
Ndrg2 T A 14: 52,147,579 (GRCm39) probably null Het
Ntsr1 T C 2: 180,142,226 (GRCm39) S6P probably damaging Het
Or5m10 T C 2: 85,717,783 (GRCm39) I213T probably benign Het
Or5p70 G A 7: 107,994,707 (GRCm39) V127I probably benign Het
Pcdhb6 A T 18: 37,467,753 (GRCm39) T225S probably benign Het
Rfng C A 11: 120,672,842 (GRCm39) V294L probably benign Het
Scml4 C T 10: 42,741,566 (GRCm39) probably benign Het
Slc5a2 A G 7: 127,869,787 (GRCm39) I407V possibly damaging Het
Strc T C 2: 121,201,295 (GRCm39) T1267A probably benign Het
Tanc1 T C 2: 59,626,341 (GRCm39) V566A probably damaging Het
Tas1r2 T C 4: 139,394,647 (GRCm39) S468P probably damaging Het
Tenm2 T A 11: 35,914,626 (GRCm39) T2304S probably benign Het
Vav3 A T 3: 109,248,557 (GRCm39) Q68L probably benign Het
Vmn2r54 C T 7: 12,363,594 (GRCm39) S433N probably benign Het
Wars1 A T 12: 108,841,047 (GRCm39) Y244N probably damaging Het
Zc3h6 A G 2: 128,835,372 (GRCm39) probably benign 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
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
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
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'- GCAGAGACTACCTCCTAAAGTTC -3'
(R):5'- ACTACGATGTCTGCGTGTGC -3'

Sequencing Primer
(F):5'- AGTTCTTATCTAGACACTGGATGCC -3'
(R):5'- TCCTACTTGGAGGGTAGCCAG -3'
Posted On 2017-01-03