Incidental Mutation 'R7348:Map3k8'
ID 570391
Institutional Source Beutler Lab
Gene Symbol Map3k8
Ensembl Gene ENSMUSG00000024235
Gene Name mitogen-activated protein kinase kinase kinase 8
Synonyms Tpl2, Cot, Cot/Tpl2, Tpl-2, c-COT
MMRRC Submission 045380-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R7348 (G1)
Quality Score 225.009
Status Validated
Chromosome 18
Chromosomal Location 4331325-4352978 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 4340561 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Leucine at position 251 (H251L)
Ref Sequence ENSEMBL: ENSMUSP00000025078 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025078] [ENSMUST00000173930]
AlphaFold Q07174
Predicted Effect probably damaging
Transcript: ENSMUST00000025078
AA Change: H251L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000025078
Gene: ENSMUSG00000024235
AA Change: H251L

DomainStartEndE-ValueType
Pfam:Pkinase 137 388 1.1e-47 PFAM
Pfam:Pkinase_Tyr 139 386 4.6e-26 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000173930
SMART Domains Protein: ENSMUSP00000133469
Gene: ENSMUSG00000024235

DomainStartEndE-ValueType
SCOP:d1phk__ 146 169 2e-4 SMART
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 98.8%
Validation Efficiency 99% (80/81)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
PHENOTYPE: Mutant mice resist endotoxic shock. Their MHC II expression is enhanced. Macrophages' TNF-alpha response to viruses and to all TLR ligands is impaired. Macrophage and T-cell secretion of other cytokines in response to various TLR ligands or OVA is aberrant. Anti-OVA Ig classes are abnormally skewed. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 79 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abra G A 15: 41,729,555 (GRCm39) R282C probably damaging Het
Adcy2 T A 13: 68,882,794 (GRCm39) E314D possibly damaging Het
Adgrl2 A T 3: 148,523,402 (GRCm39) I274N Het
Adpgk A G 9: 59,221,069 (GRCm39) I292V probably benign Het
Agtrap G T 4: 148,165,054 (GRCm39) F124L probably benign Het
Ankrd26 A G 6: 118,485,525 (GRCm39) Y1450H probably damaging Het
Ap4e1 A T 2: 126,903,896 (GRCm39) S933C probably damaging Het
Ap4e1 G T 2: 126,903,897 (GRCm39) S933I possibly damaging Het
Ap5s1 A T 2: 131,054,572 (GRCm39) T128S possibly damaging Het
Arih1 T C 9: 59,393,341 (GRCm39) Y97C probably damaging Het
Atp1a3 A G 7: 24,678,251 (GRCm39) F1034S unknown Het
Bmp6 T C 13: 38,669,879 (GRCm39) S388P probably benign Het
Ccdc39 A G 3: 33,886,825 (GRCm39) V261A possibly damaging Het
Ccdc66 C T 14: 27,222,293 (GRCm39) C150Y probably damaging Het
Cep89 G A 7: 35,129,353 (GRCm39) R630H probably damaging Het
Cln6 A G 9: 62,756,458 (GRCm39) S201G probably benign Het
Cntnap4 T C 8: 113,391,909 (GRCm39) Y125H probably damaging Het
Copa A G 1: 171,929,790 (GRCm39) T286A possibly damaging Het
Cul9 A T 17: 46,821,919 (GRCm39) I1852K possibly damaging Het
Cyp2j8 C A 4: 96,332,877 (GRCm39) A490S probably benign Het
Cyp2t4 A G 7: 26,856,676 (GRCm39) I239V probably benign Het
Dpcd A G 19: 45,560,905 (GRCm39) Y111C probably damaging Het
E2f7 C T 10: 110,616,836 (GRCm39) T692I probably damaging Het
Fastkd5 A G 2: 130,457,055 (GRCm39) Y512H probably damaging Het
Fastkd5 A C 2: 130,458,359 (GRCm39) M77R probably benign Het
Fhod3 A G 18: 25,223,524 (GRCm39) R957G possibly damaging Het
H6pd C A 4: 150,068,359 (GRCm39) probably null Het
Haus5 G T 7: 30,356,391 (GRCm39) P544Q possibly damaging Het
Ifi207 CTGTTGATGAAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATACAGTTGCTTGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATAGAGTTGCATATGGAGCCAGGAGGATGCTATATGTTGTTGATGAAGTTGCATGTGGAGCCAGGAG CTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGTTGTTGATAGAGTTGCATGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATACAGTTGCTTGTGGAGCCAGGAGGTTGCTAGATGCTGTTGATAGAGTTGCATATGGAGCCAGGAGGATGCTATATGTTGTTGATGAAGTTGCATGTGGAGCCAGGAG 1: 173,556,762 (GRCm39) probably benign Het
Igf2r A G 17: 12,922,371 (GRCm39) Y1248H probably damaging Het
Izumo3 T C 4: 92,035,455 (GRCm39) N6S possibly damaging Het
Lrp6 G T 6: 134,427,781 (GRCm39) P1604T probably damaging Het
Mapre3 T C 5: 31,019,173 (GRCm39) Y6H probably benign Het
Mlh3 G T 12: 85,314,215 (GRCm39) P657Q probably damaging Het
Mrgpra1 T C 7: 46,985,157 (GRCm39) Y174C probably benign Het
Ms4a6d G A 19: 11,567,437 (GRCm39) Q155* probably null Het
Myh1 C A 11: 67,093,365 (GRCm39) P152Q probably damaging Het
Myh6 A T 14: 55,189,716 (GRCm39) L1110Q probably damaging Het
Nf1 T A 11: 79,427,676 (GRCm39) S1778T probably benign Het
Nkpd1 G A 7: 19,258,341 (GRCm39) E707K probably damaging Het
Nlrp4a A G 7: 26,143,698 (GRCm39) E21G probably damaging Het
Nr4a3 T G 4: 48,051,290 (GRCm39) S15A possibly damaging Het
Or2f1 T C 6: 42,721,790 (GRCm39) L273S possibly damaging Het
Or5p1 T C 7: 107,916,920 (GRCm39) V273A possibly damaging Het
Or5p64 T C 7: 107,855,330 (GRCm39) D5G probably benign Het
Or7a38 A G 10: 78,753,396 (GRCm39) T241A probably damaging Het
Parg G A 14: 31,972,036 (GRCm39) R677Q possibly damaging Het
Pcsk5 A T 19: 17,434,182 (GRCm39) C1395* probably null Het
Psd2 G A 18: 36,113,389 (GRCm39) S287N possibly damaging Het
Psd3 T C 8: 68,243,583 (GRCm39) N685S possibly damaging Het
Pygb C T 2: 150,628,903 (GRCm39) T39M probably benign Het
Rbfox1 C A 16: 7,225,888 (GRCm39) Y351* probably null Het
Rftn1 A G 17: 50,311,351 (GRCm39) L396P probably damaging Het
S1pr1 A G 3: 115,505,710 (GRCm39) Y295H probably damaging Het
Scn5a T C 9: 119,364,899 (GRCm39) M440V probably benign Het
Sel1l2 T C 2: 140,107,644 (GRCm39) N240S probably benign Het
Skic3 T C 13: 76,331,003 (GRCm39) F1478L possibly damaging Het
Skint1 T C 4: 111,878,770 (GRCm39) L234P probably damaging Het
Skint11 T A 4: 114,101,919 (GRCm39) Y311N probably benign Het
Slc6a5 A T 7: 49,559,915 (GRCm39) probably benign Het
Tas2r134 T C 2: 51,518,414 (GRCm39) S298P possibly damaging Het
Tbcd C A 11: 121,485,137 (GRCm39) A773D probably benign Het
Tgoln1 G C 6: 72,593,261 (GRCm39) T73R probably benign Het
Tmem184a T C 5: 139,799,809 (GRCm39) E24G probably null Het
Tmem207 C A 16: 26,335,577 (GRCm39) W53C possibly damaging Het
Tns1 T A 1: 73,956,076 (GRCm39) H549L possibly damaging Het
Ttc41 G T 10: 86,586,212 (GRCm39) E839* probably null Het
Ufd1 T G 16: 18,634,635 (GRCm39) probably benign Het
Usp28 A G 9: 48,942,177 (GRCm39) E713G probably benign Het
Utrn A G 10: 12,623,762 (GRCm39) W159R probably damaging Het
Vcl C T 14: 21,053,218 (GRCm39) A411V probably benign Het
Vcl T A 14: 21,059,020 (GRCm39) C545* probably null Het
Vmn1r120 A T 7: 20,787,377 (GRCm39) S111R probably damaging Het
Wwox T A 8: 115,199,392 (GRCm39) C146S probably benign Het
Zbtb2 T C 10: 4,324,574 (GRCm39) T57A possibly damaging Het
Zfp362 T C 4: 128,671,010 (GRCm39) D336G possibly damaging Het
Zfp628 G A 7: 4,924,817 (GRCm39) G1013E probably damaging Het
Zfp704 A G 3: 9,539,658 (GRCm39) S231P probably damaging Het
Zhx3 G T 2: 160,624,038 (GRCm39) S43* probably null Het
Other mutations in Map3k8
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02458:Map3k8 APN 18 4,334,660 (GRCm39) missense probably damaging 1.00
IGL02483:Map3k8 APN 18 4,349,318 (GRCm39) utr 5 prime probably benign
IGL03174:Map3k8 APN 18 4,349,247 (GRCm39) missense probably damaging 1.00
Flojo UTSW 18 4,339,548 (GRCm39) missense possibly damaging 0.95
gnostic_gospel UTSW 18 4,333,965 (GRCm39) missense probably damaging 1.00
juicy UTSW 18 4,339,552 (GRCm39) missense probably damaging 0.99
Sluggish UTSW 18 4,339,608 (GRCm39) splice site probably benign
R0304:Map3k8 UTSW 18 4,339,552 (GRCm39) missense probably damaging 0.99
R0569:Map3k8 UTSW 18 4,349,162 (GRCm39) missense probably benign 0.00
R1748:Map3k8 UTSW 18 4,334,766 (GRCm39) missense probably damaging 1.00
R1793:Map3k8 UTSW 18 4,332,389 (GRCm39) nonsense probably null
R2310:Map3k8 UTSW 18 4,349,001 (GRCm39) missense probably benign
R3625:Map3k8 UTSW 18 4,333,965 (GRCm39) missense probably damaging 1.00
R4786:Map3k8 UTSW 18 4,340,647 (GRCm39) nonsense probably null
R4921:Map3k8 UTSW 18 4,349,124 (GRCm39) missense possibly damaging 0.92
R4930:Map3k8 UTSW 18 4,349,215 (GRCm39) nonsense probably null
R4934:Map3k8 UTSW 18 4,339,548 (GRCm39) missense possibly damaging 0.95
R4956:Map3k8 UTSW 18 4,339,530 (GRCm39) missense probably benign 0.00
R5241:Map3k8 UTSW 18 4,340,750 (GRCm39) missense probably damaging 0.98
R5549:Map3k8 UTSW 18 4,340,762 (GRCm39) missense probably damaging 0.98
R6317:Map3k8 UTSW 18 4,348,979 (GRCm39) critical splice donor site probably null
R6326:Map3k8 UTSW 18 4,340,651 (GRCm39) missense probably damaging 1.00
R6910:Map3k8 UTSW 18 4,340,801 (GRCm39) missense probably benign 0.03
R7010:Map3k8 UTSW 18 4,334,060 (GRCm39) missense probably damaging 1.00
R7247:Map3k8 UTSW 18 4,334,036 (GRCm39) missense probably damaging 1.00
R7300:Map3k8 UTSW 18 4,349,076 (GRCm39) missense probably damaging 0.98
R7903:Map3k8 UTSW 18 4,349,162 (GRCm39) missense probably benign 0.00
R8302:Map3k8 UTSW 18 4,334,064 (GRCm39) missense probably damaging 0.97
R8676:Map3k8 UTSW 18 4,343,137 (GRCm39) missense probably benign 0.01
R8847:Map3k8 UTSW 18 4,333,889 (GRCm39) missense
R9068:Map3k8 UTSW 18 4,340,557 (GRCm39) missense probably benign 0.36
R9352:Map3k8 UTSW 18 4,349,170 (GRCm39) missense probably benign
R9460:Map3k8 UTSW 18 4,349,277 (GRCm39) missense probably benign 0.00
R9526:Map3k8 UTSW 18 4,333,869 (GRCm39) missense probably damaging 1.00
R9548:Map3k8 UTSW 18 4,349,141 (GRCm39) missense probably benign
R9632:Map3k8 UTSW 18 4,339,546 (GRCm39) missense probably damaging 0.98
Predicted Primers PCR Primer
(F):5'- AAACACGTGGTCATCATCCTTG -3'
(R):5'- CCGGCATGAGAACATTGCTG -3'

Sequencing Primer
(F):5'- AACACGTGGTCATCATCCTTGTATTG -3'
(R):5'- AGAACATTGCTGAGTTATATGGTGCC -3'
Posted On 2019-09-13