Incidental Mutation 'R2156:Map3k5'
ID 234833
Institutional Source Beutler Lab
Gene Symbol Map3k5
Ensembl Gene ENSMUSG00000071369
Gene Name mitogen-activated protein kinase kinase kinase 5
Synonyms ASK1, 7420452D20Rik, ASK, Mekk5
MMRRC Submission 040159-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R2156 (G1)
Quality Score 225
Status Not validated
Chromosome 10
Chromosomal Location 19810218-20018499 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 19900683 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Histidine at position 286 (Y286H)
Ref Sequence ENSEMBL: ENSMUSP00000112864 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000095806] [ENSMUST00000120259] [ENSMUST00000129437] [ENSMUST00000152533]
AlphaFold O35099
Predicted Effect probably damaging
Transcript: ENSMUST00000095806
AA Change: Y294H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000093485
Gene: ENSMUSG00000071369
AA Change: Y294H

DomainStartEndE-ValueType
low complexity region 26 43 N/A INTRINSIC
low complexity region 44 58 N/A INTRINSIC
low complexity region 80 99 N/A INTRINSIC
Pfam:DUF4071 172 552 2.1e-162 PFAM
S_TKc 687 945 8.08e-92 SMART
low complexity region 1195 1207 N/A INTRINSIC
low complexity region 1225 1238 N/A INTRINSIC
coiled coil region 1251 1292 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000120259
AA Change: Y286H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000112864
Gene: ENSMUSG00000071369
AA Change: Y286H

DomainStartEndE-ValueType
low complexity region 26 43 N/A INTRINSIC
low complexity region 44 58 N/A INTRINSIC
low complexity region 80 99 N/A INTRINSIC
Pfam:DUF4071 172 544 1.7e-156 PFAM
S_TKc 679 937 8.08e-92 SMART
low complexity region 1187 1199 N/A INTRINSIC
low complexity region 1217 1230 N/A INTRINSIC
coiled coil region 1243 1284 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000129437
SMART Domains Protein: ENSMUSP00000114518
Gene: ENSMUSG00000071369

DomainStartEndE-ValueType
Pfam:Pkinase 34 144 7.6e-20 PFAM
Pfam:Pkinase_Tyr 34 144 5e-14 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000152533
SMART Domains Protein: ENSMUSP00000122553
Gene: ENSMUSG00000071369

DomainStartEndE-ValueType
Pfam:DUF4071 10 80 6.3e-23 PFAM
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.7%
  • 10x: 97.5%
  • 20x: 95.6%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutant mice are overtly normal, however apoptosis abnormalities are evident in cultured cells and after induced heart damage. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 85 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1810065E05Rik T A 11: 58,313,134 (GRCm39) probably null Het
Acaa2 T C 18: 74,926,476 (GRCm39) probably null Het
Adam7 T C 14: 68,748,792 (GRCm39) Q485R probably benign Het
Adcy4 T G 14: 56,006,627 (GRCm39) T1069P probably benign Het
Arsj T C 3: 126,232,337 (GRCm39) L361P probably damaging Het
Birc2 A C 9: 7,826,939 (GRCm39) L349R probably damaging Het
C1qa T C 4: 136,623,727 (GRCm39) Y159C probably damaging Het
Cdh13 A G 8: 119,963,703 (GRCm39) K428E probably damaging Het
Cenpe T C 3: 134,953,235 (GRCm39) M1563T probably benign Het
Col10a1 T C 10: 34,271,696 (GRCm39) V556A probably benign Het
Creg2 G A 1: 39,662,338 (GRCm39) L265F probably damaging Het
Cyp1a2 T A 9: 57,589,433 (GRCm39) D127V probably damaging Het
Cyp3a44 A T 5: 145,740,480 (GRCm39) Y53* probably null Het
Cyth1 C T 11: 118,073,634 (GRCm39) R233Q probably damaging Het
Dnmbp G A 19: 43,890,346 (GRCm39) H474Y possibly damaging Het
Dvl1 G A 4: 155,932,273 (GRCm39) V28I possibly damaging Het
Ercc2 G A 7: 19,120,717 (GRCm39) R206H possibly damaging Het
Evx2 T A 2: 74,486,360 (GRCm39) H343L probably damaging Het
Fcrl2 T A 3: 87,164,648 (GRCm39) I293F probably benign Het
Gcnt4 A G 13: 97,082,974 (GRCm39) E90G probably damaging Het
Gid8 T G 2: 180,358,751 (GRCm39) C139G probably benign Het
Gm11938 C A 11: 99,493,933 (GRCm39) C54F probably damaging Het
Gm3336 G A 8: 71,174,509 (GRCm39) V158I probably benign Het
Gucy1b1 T C 3: 81,968,327 (GRCm39) N60D probably benign Het
Hdac7 T C 15: 97,691,944 (GRCm39) K810E probably benign Het
Hsp90ab1 A G 17: 45,880,629 (GRCm39) F361L possibly damaging Het
Igf2bp3 A T 6: 49,085,858 (GRCm39) probably null Het
Inpp4b T A 8: 82,775,118 (GRCm39) I772N probably damaging Het
Iqca1 A G 1: 90,017,238 (GRCm39) L390P possibly damaging Het
Itgb2 C T 10: 77,396,082 (GRCm39) R586W probably benign Het
Itih1 A G 14: 30,655,432 (GRCm39) S588P possibly damaging Het
Iyd T A 10: 3,497,166 (GRCm39) probably null Het
Kl A G 5: 150,912,425 (GRCm39) K725E probably benign Het
Layn T A 9: 50,968,697 (GRCm39) M349L probably benign Het
Med4 C T 14: 73,755,472 (GRCm39) probably benign Het
Mfn1 T A 3: 32,588,400 (GRCm39) N42K possibly damaging Het
Mindy2 T C 9: 70,563,874 (GRCm39) D152G probably benign Het
Mrc2 A G 11: 105,238,682 (GRCm39) probably null Het
Mrpl11 C A 19: 5,012,497 (GRCm39) A26E probably damaging Het
Msh6 G A 17: 88,293,568 (GRCm39) W774* probably null Het
Mtch1 A T 17: 29,561,841 (GRCm39) V121E probably damaging Het
Mtg2 G T 2: 179,725,923 (GRCm39) E178* probably null Het
Nbas A T 12: 13,491,510 (GRCm39) N1461Y probably damaging Het
Ndfip2 A G 14: 105,525,204 (GRCm39) T65A probably benign Het
Ninl G T 2: 150,786,503 (GRCm39) Q1146K probably damaging Het
Notch1 T C 2: 26,350,873 (GRCm39) D2089G possibly damaging Het
Notch3 C T 17: 32,366,818 (GRCm39) V906M probably damaging Het
Or51l14 A G 7: 103,101,371 (GRCm39) I276V probably benign Het
Or6b6 A G 7: 106,570,775 (GRCm39) Y259H probably damaging Het
Osmr A T 15: 6,873,891 (GRCm39) Y169N probably benign Het
Ovgp1 T C 3: 105,885,033 (GRCm39) V124A possibly damaging Het
P2rx1 T C 11: 72,904,939 (GRCm39) M369T probably benign Het
Pde4dip T C 3: 97,631,534 (GRCm39) Q1125R probably damaging Het
Podn A T 4: 107,878,892 (GRCm39) V180E probably damaging Het
Pold1 A T 7: 44,188,542 (GRCm39) V475E probably damaging Het
Polg A G 7: 79,111,468 (GRCm39) I261T possibly damaging Het
Satb1 G T 17: 52,047,438 (GRCm39) Q595K probably benign Het
Scaf8 T A 17: 3,214,407 (GRCm39) probably null Het
Semp2l1 T A 1: 32,585,128 (GRCm39) M261L probably benign Het
Serpinb3a C T 1: 106,975,202 (GRCm39) probably null Het
Slc22a26 T C 19: 7,779,480 (GRCm39) D112G probably damaging Het
Slc25a23 A G 17: 57,352,562 (GRCm39) F441L probably benign Het
Slc25a53 T C X: 135,884,216 (GRCm39) T42A probably damaging Het
Slc6a15 T C 10: 103,229,269 (GRCm39) Y103H probably damaging Het
Slx4 A G 16: 3,804,223 (GRCm39) S864P probably benign Het
Snap91 T C 9: 86,707,130 (GRCm39) E220G probably damaging Het
Spam1 T C 6: 24,796,267 (GRCm39) F73L probably damaging Het
Sphkap C T 1: 83,255,710 (GRCm39) V393M probably benign Het
Spred2 T C 11: 19,971,241 (GRCm39) Y370H probably damaging Het
Sqle T C 15: 59,195,578 (GRCm39) probably null Het
Srrm2 A G 17: 24,037,237 (GRCm39) T1390A probably benign Het
Tas1r2 A G 4: 139,396,352 (GRCm39) R564G possibly damaging Het
Tbl2 G T 5: 135,185,374 (GRCm39) probably null Het
Tcof1 T C 18: 60,964,901 (GRCm39) D606G possibly damaging Het
Tdpoz3 T A 3: 93,734,087 (GRCm39) L254H probably damaging Het
Trpm1 A T 7: 63,884,736 (GRCm39) I806F probably damaging Het
Ttc22 A G 4: 106,496,237 (GRCm39) D429G probably benign Het
Ube2o C A 11: 116,471,972 (GRCm39) G90C probably damaging Het
Usp34 T A 11: 23,332,602 (GRCm39) F1110I probably damaging Het
Vmn2r82 T C 10: 79,214,722 (GRCm39) L235P probably damaging Het
Vps35 A G 8: 86,013,129 (GRCm39) V116A probably benign Het
Wdfy3 A G 5: 102,046,291 (GRCm39) probably null Het
Zeb2 T C 2: 44,878,821 (GRCm39) K1138E probably benign Het
Zfp513 G A 5: 31,357,866 (GRCm39) T169I probably benign Het
Zfp629 T C 7: 127,211,551 (GRCm39) D86G probably benign Het
Other mutations in Map3k5
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00569:Map3k5 APN 10 19,810,790 (GRCm39) missense possibly damaging 0.73
IGL00978:Map3k5 APN 10 20,017,313 (GRCm39) missense probably damaging 1.00
IGL01470:Map3k5 APN 10 19,993,933 (GRCm39) missense possibly damaging 0.89
IGL01992:Map3k5 APN 10 19,904,879 (GRCm39) nonsense probably null
IGL02479:Map3k5 APN 10 19,932,230 (GRCm39) missense probably damaging 1.00
IGL02728:Map3k5 APN 10 19,994,038 (GRCm39) missense possibly damaging 0.71
IGL02812:Map3k5 APN 10 19,900,782 (GRCm39) missense probably damaging 1.00
IGL03104:Map3k5 APN 10 20,007,801 (GRCm39) missense probably benign
P0033:Map3k5 UTSW 10 20,007,959 (GRCm39) splice site probably benign
PIT4434001:Map3k5 UTSW 10 19,902,003 (GRCm39) missense probably damaging 0.98
R0284:Map3k5 UTSW 10 19,876,359 (GRCm39) missense probably damaging 0.99
R1103:Map3k5 UTSW 10 19,899,422 (GRCm39) missense probably benign 0.00
R1172:Map3k5 UTSW 10 19,932,394 (GRCm39) intron probably benign
R1250:Map3k5 UTSW 10 19,986,521 (GRCm39) missense possibly damaging 0.73
R1493:Map3k5 UTSW 10 19,904,859 (GRCm39) missense probably damaging 1.00
R1634:Map3k5 UTSW 10 20,012,657 (GRCm39) missense possibly damaging 0.64
R1693:Map3k5 UTSW 10 19,979,988 (GRCm39) missense probably damaging 1.00
R1713:Map3k5 UTSW 10 19,986,593 (GRCm39) missense possibly damaging 0.79
R1832:Map3k5 UTSW 10 19,975,306 (GRCm39) missense probably damaging 1.00
R1844:Map3k5 UTSW 10 19,979,909 (GRCm39) missense probably benign 0.33
R1869:Map3k5 UTSW 10 20,007,855 (GRCm39) nonsense probably null
R2214:Map3k5 UTSW 10 19,902,035 (GRCm39) critical splice donor site probably null
R2221:Map3k5 UTSW 10 19,943,666 (GRCm39) missense possibly damaging 0.96
R2223:Map3k5 UTSW 10 19,943,666 (GRCm39) missense possibly damaging 0.96
R2249:Map3k5 UTSW 10 20,003,443 (GRCm39) missense probably damaging 0.99
R2418:Map3k5 UTSW 10 19,986,603 (GRCm39) missense probably benign 0.02
R2513:Map3k5 UTSW 10 19,970,201 (GRCm39) missense possibly damaging 0.92
R3014:Map3k5 UTSW 10 19,970,175 (GRCm39) missense probably damaging 1.00
R3770:Map3k5 UTSW 10 19,900,765 (GRCm39) missense probably damaging 0.99
R3814:Map3k5 UTSW 10 19,901,936 (GRCm39) missense probably damaging 0.99
R3814:Map3k5 UTSW 10 20,016,426 (GRCm39) missense probably damaging 0.99
R4706:Map3k5 UTSW 10 19,934,684 (GRCm39) missense probably damaging 1.00
R4749:Map3k5 UTSW 10 20,007,798 (GRCm39) missense probably benign 0.42
R4903:Map3k5 UTSW 10 19,994,235 (GRCm39) missense probably null 1.00
R4958:Map3k5 UTSW 10 19,899,535 (GRCm39) missense possibly damaging 0.79
R5065:Map3k5 UTSW 10 19,958,213 (GRCm39) missense probably damaging 1.00
R5210:Map3k5 UTSW 10 19,900,647 (GRCm39) missense possibly damaging 0.82
R5245:Map3k5 UTSW 10 20,016,437 (GRCm39) missense probably benign 0.00
R5304:Map3k5 UTSW 10 19,983,984 (GRCm39) missense probably benign 0.13
R5428:Map3k5 UTSW 10 19,899,399 (GRCm39) missense possibly damaging 0.93
R5566:Map3k5 UTSW 10 19,986,465 (GRCm39) missense probably damaging 1.00
R5914:Map3k5 UTSW 10 19,980,001 (GRCm39) missense probably benign 0.24
R6155:Map3k5 UTSW 10 19,994,187 (GRCm39) missense probably benign 0.01
R6161:Map3k5 UTSW 10 19,876,321 (GRCm39) missense probably damaging 0.98
R6191:Map3k5 UTSW 10 19,899,415 (GRCm39) missense probably damaging 0.99
R6251:Map3k5 UTSW 10 20,014,006 (GRCm39) splice site probably null
R6800:Map3k5 UTSW 10 20,017,326 (GRCm39) makesense probably null
R7304:Map3k5 UTSW 10 19,975,301 (GRCm39) missense probably damaging 1.00
R7722:Map3k5 UTSW 10 20,007,891 (GRCm39) missense probably benign 0.04
R8058:Map3k5 UTSW 10 20,007,860 (GRCm39) missense probably damaging 0.99
R8207:Map3k5 UTSW 10 19,986,612 (GRCm39) frame shift probably null
R8827:Map3k5 UTSW 10 19,902,003 (GRCm39) missense probably damaging 0.98
R8977:Map3k5 UTSW 10 19,955,000 (GRCm39) missense possibly damaging 0.88
R9490:Map3k5 UTSW 10 20,007,797 (GRCm39) missense probably benign
R9570:Map3k5 UTSW 10 19,876,314 (GRCm39) missense probably benign 0.02
R9784:Map3k5 UTSW 10 19,810,812 (GRCm39) missense probably damaging 1.00
RF024:Map3k5 UTSW 10 19,975,918 (GRCm39) missense probably damaging 1.00
X0017:Map3k5 UTSW 10 19,994,180 (GRCm39) missense probably damaging 0.98
Predicted Primers PCR Primer
(F):5'- GGGATAATTTGCACTCGAGTTAGTAAG -3'
(R):5'- ACCTAGCTGTCGGTCTACAC -3'

Sequencing Primer
(F):5'- GGACTCCCAAATTTGTTAATAATGCC -3'
(R):5'- TCGGTCTACACCCGCGTC -3'
Posted On 2014-10-01