Incidental Mutation 'R0304:Map3k8'
ID 37804
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 038515-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0304 (G1)
Quality Score 225
Status Validated
Chromosome 18
Chromosomal Location 4331325-4352978 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to C at 4339552 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Arginine at position 273 (L273R)
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: L273R

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000025078
Gene: ENSMUSG00000024235
AA Change: L273R

DomainStartEndE-ValueType
Pfam:Pkinase 137 388 1.1e-47 PFAM
Pfam:Pkinase_Tyr 139 386 4.6e-26 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000105472
Predicted Effect noncoding transcript
Transcript: ENSMUST00000173708
Predicted Effect probably benign
Transcript: ENSMUST00000173930
SMART Domains Protein: ENSMUSP00000133469
Gene: ENSMUSG00000024235

DomainStartEndE-ValueType
SCOP:d1phk__ 146 169 2e-4 SMART
Meta Mutation Damage Score 0.9604 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.2%
  • 20x: 95.3%
Validation Efficiency 98% (95/97)
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: 93 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aadacl4fm1 C T 4: 144,246,619 (GRCm39) T55I probably benign Het
Acod1 T A 14: 103,292,418 (GRCm39) I314N probably damaging Het
Actl11 T A 9: 107,806,967 (GRCm39) V430E probably damaging Het
Adam19 A C 11: 46,018,219 (GRCm39) D427A possibly damaging Het
Adarb2 C T 13: 8,802,606 (GRCm39) probably benign Het
Akap7 A T 10: 25,147,450 (GRCm39) H93Q probably damaging Het
Ankrd36 C A 11: 5,578,981 (GRCm39) R82S possibly damaging Het
Arhgap21 A T 2: 20,864,612 (GRCm39) probably benign Het
Atm T A 9: 53,427,644 (GRCm39) I489F probably benign Het
Carmil1 T C 13: 24,323,324 (GRCm39) S243G probably damaging Het
Cdc42bpg T C 19: 6,367,278 (GRCm39) V939A probably damaging Het
Cel A C 2: 28,447,783 (GRCm39) L377R probably benign Het
Clock A G 5: 76,374,832 (GRCm39) V779A unknown Het
Cluap1 G A 16: 3,747,782 (GRCm39) probably benign Het
Ctif A T 18: 75,654,889 (GRCm39) H212Q probably benign Het
Cyp4a29 T A 4: 115,110,129 (GRCm39) probably benign Het
Cytip T C 2: 58,038,258 (GRCm39) N101S possibly damaging Het
D130043K22Rik T C 13: 25,048,798 (GRCm39) M434T probably benign Het
Ddx47 A G 6: 134,994,183 (GRCm39) I154V possibly damaging Het
Dnah6 C T 6: 73,136,098 (GRCm39) E1014K probably damaging Het
Dnajc27 T G 12: 4,156,793 (GRCm39) probably benign Het
Drc7 A T 8: 95,785,756 (GRCm39) D204V probably damaging Het
Dsc3 A G 18: 20,114,298 (GRCm39) Y319H probably damaging Het
Eml6 T C 11: 29,727,441 (GRCm39) Q1227R probably benign Het
Enpp2 A T 15: 54,741,202 (GRCm39) D365E probably benign Het
Ercc2 T C 7: 19,120,633 (GRCm39) I199T possibly damaging Het
Exd2 G A 12: 80,538,014 (GRCm39) probably benign Het
F2 A T 2: 91,463,578 (GRCm39) I128N probably damaging Het
Fam219b T C 9: 57,446,159 (GRCm39) L123P probably damaging Het
Fasn A G 11: 120,710,762 (GRCm39) V299A possibly damaging Het
Fastkd2 T C 1: 63,791,559 (GRCm39) V689A possibly damaging Het
Fbxw13 C T 9: 109,023,789 (GRCm39) R85Q probably benign Het
Fer1l6 A G 15: 58,462,411 (GRCm39) Y822C probably benign Het
Fhl5 T C 4: 25,207,241 (GRCm39) T176A probably benign Het
Gm20530 T G 17: 36,405,118 (GRCm39) noncoding transcript Het
Gm4787 A T 12: 81,425,708 (GRCm39) I150N probably damaging Het
Grip1 G A 10: 119,911,376 (GRCm39) S618N probably benign Het
Hdac9 T C 12: 34,424,110 (GRCm39) K454E probably damaging Het
Iars2 T A 1: 185,019,353 (GRCm39) I978F possibly damaging Het
Icosl A G 10: 77,911,156 (GRCm39) Y299C probably benign Het
Idi1 T C 13: 8,940,393 (GRCm39) Y192H probably damaging Het
Iqub T G 6: 24,454,290 (GRCm39) Q531P probably damaging Het
Itih4 T A 14: 30,612,051 (GRCm39) probably null Het
Izumo4 A T 10: 80,538,770 (GRCm39) H71L probably damaging Het
Jcad A T 18: 4,673,325 (GRCm39) E362D possibly damaging Het
Kif21a G T 15: 90,860,724 (GRCm39) probably null Het
Kynu A T 2: 43,569,893 (GRCm39) I392F probably damaging Het
Luc7l2 A G 6: 38,569,711 (GRCm39) E223G probably damaging Het
Max A G 12: 76,985,361 (GRCm39) L119P probably benign Het
Mphosph9 T C 5: 124,436,892 (GRCm39) N484S probably benign Het
Mrgprg A G 7: 143,318,792 (GRCm39) Y107H probably damaging Het
Mrps31 A T 8: 22,911,354 (GRCm39) I199F probably benign Het
Mtr C G 13: 12,237,040 (GRCm39) probably null Het
Muc6 G A 7: 141,218,313 (GRCm39) S2120F possibly damaging Het
Nkapd1 T C 9: 50,519,222 (GRCm39) D130G probably damaging Het
Nptx2 A G 5: 144,490,460 (GRCm39) probably benign Het
Nrip1 T C 16: 76,089,595 (GRCm39) Q654R possibly damaging Het
Ocm A G 5: 143,961,352 (GRCm39) F30L probably damaging Het
Oosp1 T C 19: 11,668,333 (GRCm39) M17V probably benign Het
Or14c45 C T 7: 86,176,195 (GRCm39) P77S probably damaging Het
Or4c111 G A 2: 88,843,632 (GRCm39) R259W probably damaging Het
Or4c118 A C 2: 88,975,108 (GRCm39) Y86* probably null Het
Or52ad1 G T 7: 102,995,918 (GRCm39) D72E probably damaging Het
Pax1 A T 2: 147,208,067 (GRCm39) Y225F probably benign Het
Pde4dip T A 3: 97,751,028 (GRCm39) H62L probably benign Het
Pkd1 C A 17: 24,804,920 (GRCm39) Q3190K probably damaging Het
Pkn1 A C 8: 84,410,236 (GRCm39) probably benign Het
Plin5 T C 17: 56,422,597 (GRCm39) D113G probably damaging Het
Ppfia1 A G 7: 144,036,082 (GRCm39) V1141A probably damaging Het
Ppp4r1 T A 17: 66,123,001 (GRCm39) D334E probably benign Het
Ptov1 A T 7: 44,512,873 (GRCm39) probably null Het
Rab22a G A 2: 173,503,252 (GRCm39) V22M probably damaging Het
Rictor T A 15: 6,815,852 (GRCm39) probably null Het
Sart1 G T 19: 5,430,559 (GRCm39) probably benign Het
Scn11a G A 9: 119,648,928 (GRCm39) A45V probably benign Het
Serpina5 A G 12: 104,069,459 (GRCm39) T224A possibly damaging Het
Siglecf G T 7: 43,001,825 (GRCm39) G212C probably damaging Het
Slc38a4 A T 15: 96,906,335 (GRCm39) M378K probably damaging Het
Spata22 T A 11: 73,231,275 (GRCm39) C176* probably null Het
Tmc3 G A 7: 83,245,347 (GRCm39) E131K probably damaging Het
Trappc10 A T 10: 78,046,594 (GRCm39) probably benign Het
Uvrag A G 7: 98,537,180 (GRCm39) F672L probably benign Het
Vmn1r121 A G 7: 20,832,332 (GRCm39) V36A possibly damaging Het
Vmn1r13 A T 6: 57,187,611 (GRCm39) M257L probably benign Het
Vmn1r58 C T 7: 5,413,495 (GRCm39) C245Y probably damaging Het
Vmn1r86 C A 7: 12,836,707 (GRCm39) M56I probably benign Het
Wdr62 T C 7: 29,942,299 (GRCm39) Y1051C probably benign Het
Xpnpep3 A G 15: 81,314,915 (GRCm39) D205G probably damaging Het
Zdhhc14 T C 17: 5,775,611 (GRCm39) probably benign Het
Zfp607a A T 7: 27,578,637 (GRCm39) D569V possibly damaging Het
Zfp609 C T 9: 65,608,470 (GRCm39) E1137K possibly damaging Het
Zfp871 T C 17: 32,993,408 (GRCm39) Y589C probably damaging Het
Zzef1 A T 11: 72,771,450 (GRCm39) D1644V probably benign 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
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
R7348:Map3k8 UTSW 18 4,340,561 (GRCm39) missense probably damaging 1.00
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'- TGTTCTGGTGACAACGATCATCCAATG -3'
(R):5'- GAAGCCAAAACCGTGAGCTTTCC -3'

Sequencing Primer
(F):5'- AATGTTGCCATTTTGTCCCC -3'
(R):5'- ACACTAGGTGGGTTCCTGAC -3'
Posted On 2013-05-23