Incidental Mutation 'R4523:Map3k3'
Institutional Source Beutler Lab
Gene Symbol Map3k3
Ensembl Gene ENSMUSG00000020700
Gene Namemitogen-activated protein kinase kinase kinase 3
SynonymsMAPKKK3, Mekk3
MMRRC Submission 042004-MU
Accession Numbers
Is this an essential gene? Essential (E-score: 1.000) question?
Stock #R4523 (G1)
Quality Score225
Status Validated
Chromosomal Location106084613-106155446 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) G to A at 106148868 bp
Amino Acid Change Arginine to Histidine at position 278 (R278H)
Ref Sequence ENSEMBL: ENSMUSP00000002044 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000002044]
Predicted Effect probably damaging
Transcript: ENSMUST00000002044
AA Change: R278H

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000002044
Gene: ENSMUSG00000020700
AA Change: R278H

PB1 44 123 1.04e-18 SMART
S_TKc 362 622 4.23e-95 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000124449
Predicted Effect noncoding transcript
Transcript: ENSMUST00000129793
Meta Mutation Damage Score 0.3782 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.2%
Validation Efficiency 100% (61/61)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die as embryos before E11.5. vascular remodeling does not take place normally. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 54 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Atp8a1 G T 5: 67,667,600 T796K probably benign Het
Atr T C 9: 95,862,863 S78P probably damaging Het
BC017643 A G 11: 121,224,108 probably benign Het
Calb2 C T 8: 110,148,509 probably null Het
Ccdc88c G T 12: 100,913,332 S1843R possibly damaging Het
Cdca7 A G 2: 72,479,698 S77G probably damaging Het
Cnot2 C T 10: 116,581,474 probably benign Het
Cstf2t T A 19: 31,083,082 V6D possibly damaging Het
Dido1 T C 2: 180,672,292 I852V probably damaging Het
Dmgdh C T 13: 93,688,630 Q154* probably null Het
Dnah12 T C 14: 26,770,022 F1138S probably damaging Het
Dnah12 G A 14: 26,876,958 A998T possibly damaging Het
Dusp5 T G 19: 53,537,601 Y225D probably damaging Het
Fam122c G A X: 53,293,499 R94H possibly damaging Het
Fam126a T C 5: 23,965,122 T410A probably benign Het
Fam193a G A 5: 34,443,371 D601N probably benign Het
Fbxo41 A G 6: 85,484,042 I228T probably damaging Het
Fmo2 T C 1: 162,887,708 K115R probably benign Het
Gak G T 5: 108,576,566 Q1093K probably benign Het
Gm5277 G T 3: 78,892,186 noncoding transcript Het
Gm7173 A T X: 79,509,995 N291K possibly damaging Het
Hgsnat A G 8: 25,968,361 probably null Het
Mrvi1 T C 7: 110,923,841 M338V probably benign Het
Muc4 T C 16: 32,736,336 probably benign Het
Nectin3 C A 16: 46,448,590 R483L probably benign Het
Nop2 G T 6: 125,133,552 R47L probably damaging Het
Ntng1 A G 3: 109,934,996 S154P probably damaging Het
Olfml2b T C 1: 170,669,222 I474T probably benign Het
Olfr1054 C G 2: 86,333,300 D19H probably benign Het
Olfr843 T C 9: 19,249,229 T57A probably damaging Het
Optc G T 1: 133,903,754 T138K possibly damaging Het
Orc4 G A 2: 48,937,489 P31S probably benign Het
Pard3 C T 8: 127,398,627 P421S probably benign Het
Pcdhb22 G T 18: 37,520,421 E647D probably benign Het
Pclo A G 5: 14,679,992 probably benign Het
Prkce G T 17: 86,490,750 probably null Het
Prr12 T C 7: 45,048,523 D656G unknown Het
Ptprk A T 10: 28,466,052 D485V probably damaging Het
Ptprn2 T C 12: 116,876,000 L381P probably damaging Het
Rnf144b T C 13: 47,207,537 I51T probably benign Het
Rpl10l T C 12: 66,283,738 D207G probably benign Het
Sh3glb2 A T 2: 30,350,699 V118E probably damaging Het
Sipa1l2 C T 8: 125,492,424 G58D probably damaging Het
Slc5a4a C T 10: 76,148,362 A46V probably damaging Het
Tepp T A 8: 95,313,010 Y18* probably null Het
Tgm7 C A 2: 121,098,588 probably null Het
Tjap1 A G 17: 46,258,792 V424A probably benign Het
Trpm6 A T 19: 18,796,500 I414F probably damaging Het
Tsr3 C G 17: 25,241,749 D196E probably benign Het
Ubqlnl C T 7: 104,149,718 V191M probably benign Het
Vmn2r72 T A 7: 85,751,926 H95L probably benign Het
Vmn2r97 T A 17: 18,929,071 N240K probably benign Het
Xdh C A 17: 73,898,344 G1042V probably damaging Het
Zcchc4 A G 5: 52,784,067 D68G probably damaging Het
Other mutations in Map3k3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01368:Map3k3 APN 11 106150389 missense probably benign 0.01
IGL03028:Map3k3 APN 11 106110751 missense probably damaging 1.00
BB003:Map3k3 UTSW 11 106145722 missense probably damaging 1.00
BB013:Map3k3 UTSW 11 106145722 missense probably damaging 1.00
R0421:Map3k3 UTSW 11 106148915 splice site probably benign
R0963:Map3k3 UTSW 11 106123792 missense probably benign 0.01
R3547:Map3k3 UTSW 11 106142553 nonsense probably null
R5627:Map3k3 UTSW 11 106148602 missense probably benign 0.03
R5747:Map3k3 UTSW 11 106150410 missense probably benign 0.03
R5925:Map3k3 UTSW 11 106149550 missense probably benign 0.07
R6141:Map3k3 UTSW 11 106097048 missense probably benign 0.27
R6394:Map3k3 UTSW 11 106148883 missense probably benign
R6714:Map3k3 UTSW 11 106114222 missense possibly damaging 0.52
R7926:Map3k3 UTSW 11 106145722 missense probably damaging 1.00
Z1088:Map3k3 UTSW 11 106150353 missense possibly damaging 0.91
Predicted Primers PCR Primer

Sequencing Primer
Posted On2015-08-18