Incidental Mutation 'R7352:Map4k4'
ID 570606
Institutional Source Beutler Lab
Gene Symbol Map4k4
Ensembl Gene ENSMUSG00000026074
Gene Name mitogen-activated protein kinase kinase kinase kinase 4
Synonyms 9430080K19Rik, Nik
MMRRC Submission 045438-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7352 (G1)
Quality Score 225.009
Status Not validated
Chromosome 1
Chromosomal Location 39900913-40026310 bp(+) (GRCm38)
Type of Mutation missense
DNA Base Change (assembly) T to A at 39962227 bp (GRCm38)
Zygosity Heterozygous
Amino Acid Change Valine to Aspartic acid at position 58 (V58D)
Ref Sequence ENSEMBL: ENSMUSP00000141862 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000163854] [ENSMUST00000168431] [ENSMUST00000191761] [ENSMUST00000192509] [ENSMUST00000193682] [ENSMUST00000195259] [ENSMUST00000195636] [ENSMUST00000195860]
AlphaFold no structure available at present
Predicted Effect unknown
Transcript: ENSMUST00000163854
AA Change: V58D
SMART Domains Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: V58D

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 687 698 N/A INTRINSIC
low complexity region 721 747 N/A INTRINSIC
low complexity region 754 763 N/A INTRINSIC
low complexity region 811 837 N/A INTRINSIC
low complexity region 891 904 N/A INTRINSIC
low complexity region 919 929 N/A INTRINSIC
CNH 970 1268 2.76e-127 SMART
Predicted Effect
SMART Domains Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: V58D

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 633 644 N/A INTRINSIC
low complexity region 667 693 N/A INTRINSIC
low complexity region 700 709 N/A INTRINSIC
low complexity region 757 783 N/A INTRINSIC
low complexity region 837 850 N/A INTRINSIC
low complexity region 865 875 N/A INTRINSIC
CNH 916 1214 2.76e-127 SMART
Predicted Effect unknown
Transcript: ENSMUST00000191761
AA Change: V58D
SMART Domains Protein: ENSMUSP00000141332
Gene: ENSMUSG00000026074
AA Change: V58D

DomainStartEndE-ValueType
S_TKc 25 289 3.4e-97 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 404 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000192509
AA Change: V58D

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: V58D

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 633 644 N/A INTRINSIC
low complexity region 667 693 N/A INTRINSIC
low complexity region 700 709 N/A INTRINSIC
low complexity region 757 783 N/A INTRINSIC
low complexity region 837 850 N/A INTRINSIC
low complexity region 865 875 N/A INTRINSIC
CNH 916 1214 2.76e-127 SMART
Predicted Effect unknown
Transcript: ENSMUST00000193682
AA Change: V58D
SMART Domains Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: V58D

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 556 567 N/A INTRINSIC
low complexity region 590 616 N/A INTRINSIC
low complexity region 623 632 N/A INTRINSIC
low complexity region 680 706 N/A INTRINSIC
low complexity region 785 814 N/A INTRINSIC
low complexity region 824 837 N/A INTRINSIC
low complexity region 852 862 N/A INTRINSIC
CNH 903 1201 2.76e-127 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000195259
AA Change: V58D

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: V58D

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 610 621 N/A INTRINSIC
low complexity region 644 670 N/A INTRINSIC
low complexity region 677 686 N/A INTRINSIC
low complexity region 731 757 N/A INTRINSIC
low complexity region 811 824 N/A INTRINSIC
low complexity region 839 849 N/A INTRINSIC
CNH 890 1188 2.76e-127 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000195636
AA Change: V58D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: V58D

DomainStartEndE-ValueType
S_TKc 25 289 3.4e-97 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 610 621 N/A INTRINSIC
low complexity region 644 670 N/A INTRINSIC
low complexity region 677 686 N/A INTRINSIC
low complexity region 731 757 N/A INTRINSIC
low complexity region 836 865 N/A INTRINSIC
low complexity region 875 888 N/A INTRINSIC
low complexity region 903 913 N/A INTRINSIC
CNH 954 1252 1.4e-129 SMART
Predicted Effect unknown
Transcript: ENSMUST00000195860
AA Change: V58D
SMART Domains Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: V58D

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 687 698 N/A INTRINSIC
low complexity region 721 747 N/A INTRINSIC
low complexity region 754 763 N/A INTRINSIC
low complexity region 811 837 N/A INTRINSIC
low complexity region 891 904 N/A INTRINSIC
low complexity region 919 929 N/A INTRINSIC
CNH 970 1268 2.76e-127 SMART
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.4%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die as embryos around day E9.5-10.5. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 100 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
AA792892 A T 5: 94,383,884 (GRCm38) N209I probably damaging Het
Abca17 C T 17: 24,289,054 (GRCm38) W1124* probably null Het
Acap3 G A 4: 155,905,711 (GRCm38) V783I possibly damaging Het
Alkbh8 A G 9: 3,345,796 (GRCm38) K172R probably damaging Het
Ankrd28 A G 14: 31,708,041 (GRCm38) L860P probably damaging Het
Arap3 G A 18: 37,973,278 (GRCm38) T1504I probably benign Het
Atad5 T C 11: 80,103,343 (GRCm38) probably null Het
Atp8a2 A G 14: 59,791,204 (GRCm38) V938A probably benign Het
AW551984 T C 9: 39,592,925 (GRCm38) M582V probably benign Het
Axdnd1 C T 1: 156,382,477 (GRCm38) V408I possibly damaging Het
Babam2 T A 5: 32,007,250 (GRCm38) Y326* probably null Het
Baiap2l1 T C 5: 144,324,626 (GRCm38) M20V probably benign Het
Bex6 A G 16: 32,186,216 (GRCm38) probably benign Het
Bicc1 G T 10: 70,947,900 (GRCm38) T469K probably benign Het
Cad T A 5: 31,058,078 (GRCm38) S78T probably damaging Het
Ccdc171 T A 4: 83,818,023 (GRCm38) D1210E possibly damaging Het
Ccnd1 T C 7: 144,937,387 (GRCm38) I161V possibly damaging Het
Cdc42bpb A T 12: 111,299,311 (GRCm38) F1396I probably damaging Het
Cep170 A T 1: 176,769,857 (GRCm38) D373E probably benign Het
Chrna4 A T 2: 181,037,474 (GRCm38) I60N probably damaging Het
Cntn2 T C 1: 132,522,399 (GRCm38) T586A probably benign Het
Csmd2 G T 4: 128,557,636 (GRCm38) V3396F Het
Cyp3a44 T A 5: 145,803,688 (GRCm38) L47F probably benign Het
D7Ertd443e A T 7: 134,349,394 (GRCm38) H183Q probably benign Het
Ddx27 T C 2: 167,029,513 (GRCm38) V510A probably benign Het
Ddx58 T A 4: 40,239,668 (GRCm38) Q10L probably benign Het
Dgat1 G T 15: 76,502,824 (GRCm38) C396* probably null Het
Dmpk A G 7: 19,086,072 (GRCm38) S83G probably damaging Het
Dsc2 T G 18: 20,035,335 (GRCm38) D689A probably benign Het
Eppk1 A T 15: 76,106,418 (GRCm38) W2088R probably benign Het
Exph5 A C 9: 53,375,722 (GRCm38) I1368L probably benign Het
Fadd T C 7: 144,580,659 (GRCm38) K163R probably benign Het
Fam149a T A 8: 45,340,997 (GRCm38) Q759L probably damaging Het
Foxo6 A T 4: 120,268,251 (GRCm38) M449K probably benign Het
Gad1 T C 2: 70,594,750 (GRCm38) F463L probably benign Het
Gad2 T A 2: 22,623,823 (GRCm38) F91I probably benign Het
Gcc2 T C 10: 58,280,698 (GRCm38) probably null Het
Gjc1 A C 11: 102,800,452 (GRCm38) C242G probably damaging Het
Gkn1 T C 6: 87,348,118 (GRCm38) E103G possibly damaging Het
Gm867 T C 10: 75,939,836 (GRCm38) T39A probably benign Het
Gpr108 A G 17: 57,236,944 (GRCm38) Y421H probably damaging Het
Gramd1b A C 9: 40,307,993 (GRCm38) V508G probably damaging Het
Grm1 A T 10: 10,719,493 (GRCm38) I797N probably damaging Het
Ice1 G A 13: 70,606,102 (GRCm38) Q622* probably null Het
Kcnb2 T A 1: 15,710,611 (GRCm38) V569E probably benign Het
Ksr2 T G 5: 117,689,641 (GRCm38) I495S probably benign Het
Litaf A T 16: 10,963,353 (GRCm38) M94K probably damaging Het
Lmod2 T C 6: 24,598,111 (GRCm38) S77P possibly damaging Het
Lrp2 G T 2: 69,472,397 (GRCm38) S2996Y probably benign Het
Ltf T C 9: 111,028,450 (GRCm38) S436P probably benign Het
Mapkapk3 C A 9: 107,257,070 (GRCm38) D332Y possibly damaging Het
Mroh1 C A 15: 76,451,474 (GRCm38) P1439Q probably benign Het
Ncor1 A G 11: 62,333,911 (GRCm38) V841A probably damaging Het
Nrxn3 A G 12: 88,850,293 (GRCm38) M248V probably benign Het
Olfr1000 T C 2: 85,608,784 (GRCm38) N42S probably damaging Het
Olfr1208 T A 2: 88,896,718 (GRCm38) N293I probably damaging Het
Olfr1238 T C 2: 89,406,462 (GRCm38) M206V probably benign Het
Olfr1239 C A 2: 89,417,967 (GRCm38) G149W probably damaging Het
Olfr1443 A G 19: 12,680,751 (GRCm38) I214M possibly damaging Het
Olfr523 A T 7: 140,176,525 (GRCm38) Y135F probably damaging Het
Olig2 A G 16: 91,226,689 (GRCm38) D97G probably benign Het
Pcdha11 T A 18: 37,006,845 (GRCm38) V509E probably damaging Het
Pglyrp3 G A 3: 92,014,640 (GRCm38) W5* probably null Het
Phf14 A T 6: 11,961,638 (GRCm38) N425Y probably damaging Het
Phf3 G T 1: 30,804,326 (GRCm38) R1851S possibly damaging Het
Pigs A G 11: 78,328,812 (GRCm38) T39A probably damaging Het
Plin4 A G 17: 56,104,427 (GRCm38) M868T probably benign Het
Pnma2 A G 14: 66,916,421 (GRCm38) Q98R possibly damaging Het
Ppp4r3a G A 12: 101,041,832 (GRCm38) T782I probably damaging Het
Prickle2 T G 6: 92,410,890 (GRCm38) E566D probably benign Het
Pvr A G 7: 19,910,616 (GRCm38) I331T possibly damaging Het
Ranbp3l A T 15: 8,968,358 (GRCm38) probably benign Het
Rapgef4 T A 2: 72,180,091 (GRCm38) I331N probably damaging Het
Reg3g C T 6: 78,466,859 (GRCm38) W122* probably null Het
Rlbp1 A T 7: 79,381,680 (GRCm38) I100N probably damaging Het
Rnf213 T A 11: 119,443,579 (GRCm38) Y3206N Het
Rsf1 CGGCGGCGG CGGCGGCGGGGGCGGCGG 7: 97,579,926 (GRCm38) probably benign Het
Rtl6 G T 15: 84,556,980 (GRCm38) R72S possibly damaging Het
Rufy3 T A 5: 88,637,194 (GRCm38) D408E possibly damaging Het
Scn3a T C 2: 65,525,701 (GRCm38) I230V possibly damaging Het
Slc23a4 A T 6: 34,948,279 (GRCm38) I507N possibly damaging Het
Slc4a8 A G 15: 100,790,984 (GRCm38) T392A probably damaging Het
Spaca7 T A 8: 12,585,742 (GRCm38) I86K probably benign Het
Syt10 G T 15: 89,814,456 (GRCm38) D228E probably benign Het
Tbx3 T A 5: 119,677,560 (GRCm38) N308K probably benign Het
Telo2 A G 17: 25,102,069 (GRCm38) V724A probably damaging Het
Tfip11 T C 5: 112,333,268 (GRCm38) V370A probably benign Het
Thbs3 A G 3: 89,225,280 (GRCm38) E843G probably benign Het
Tmprss11g T C 5: 86,496,542 (GRCm38) I148V not run Het
Trbv14 T A 6: 41,135,495 (GRCm38) D75E possibly damaging Het
Trio A G 15: 27,732,876 (GRCm38) V2973A probably damaging Het
Ttn T C 2: 76,794,484 (GRCm38) D15250G probably damaging Het
Ubr2 G A 17: 46,930,426 (GRCm38) T1734I probably benign Het
Ush2a G T 1: 188,466,124 (GRCm38) A1462S probably benign Het
Ushbp1 T G 8: 71,388,881 (GRCm38) T435P possibly damaging Het
Vps13c T C 9: 67,840,446 (GRCm38) V7A possibly damaging Het
Wnk4 T C 11: 101,264,418 (GRCm38) V385A probably damaging Het
Wnt2b C T 3: 104,947,177 (GRCm38) V322I probably benign Het
Zbtb8a C T 4: 129,360,081 (GRCm38) V207M probably benign Het
Zc3hav1l A G 6: 38,298,981 (GRCm38) M87T probably benign Het
Other mutations in Map4k4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00328:Map4k4 APN 1 40,004,816 (GRCm38) missense probably damaging 0.99
IGL00417:Map4k4 APN 1 40,014,532 (GRCm38) missense possibly damaging 0.92
IGL00516:Map4k4 APN 1 40,014,602 (GRCm38) missense probably damaging 1.00
IGL01545:Map4k4 APN 1 40,014,229 (GRCm38) splice site probably benign
IGL02092:Map4k4 APN 1 40,024,348 (GRCm38) missense probably damaging 1.00
IGL02092:Map4k4 APN 1 39,986,783 (GRCm38) missense probably benign 0.12
IGL02570:Map4k4 APN 1 39,980,579 (GRCm38) missense probably benign 0.06
IGL02626:Map4k4 APN 1 40,014,097 (GRCm38) splice site probably benign
IGL02993:Map4k4 APN 1 40,014,188 (GRCm38) missense probably damaging 0.98
IGL03178:Map4k4 APN 1 39,986,693 (GRCm38) missense possibly damaging 0.63
tank UTSW 1 40,004,864 (GRCm38) missense possibly damaging 0.93
IGL02835:Map4k4 UTSW 1 40,010,600 (GRCm38) missense probably damaging 0.99
R0496:Map4k4 UTSW 1 40,006,822 (GRCm38) missense probably damaging 0.99
R0498:Map4k4 UTSW 1 39,990,178 (GRCm38) missense probably benign 0.22
R0588:Map4k4 UTSW 1 40,004,864 (GRCm38) missense possibly damaging 0.93
R0674:Map4k4 UTSW 1 40,003,815 (GRCm38) missense probably damaging 1.00
R1205:Map4k4 UTSW 1 40,003,844 (GRCm38) missense probably damaging 1.00
R1349:Map4k4 UTSW 1 40,021,159 (GRCm38) missense probably damaging 1.00
R1615:Map4k4 UTSW 1 40,006,830 (GRCm38) splice site probably benign
R1763:Map4k4 UTSW 1 40,000,757 (GRCm38) splice site probably benign
R1800:Map4k4 UTSW 1 40,023,460 (GRCm38) missense probably damaging 1.00
R1893:Map4k4 UTSW 1 40,001,557 (GRCm38) missense probably benign 0.08
R2411:Map4k4 UTSW 1 40,007,496 (GRCm38) missense probably damaging 0.96
R2851:Map4k4 UTSW 1 40,000,755 (GRCm38) splice site probably benign
R2852:Map4k4 UTSW 1 40,000,755 (GRCm38) splice site probably benign
R2987:Map4k4 UTSW 1 39,986,765 (GRCm38) missense probably damaging 1.00
R3087:Map4k4 UTSW 1 40,021,082 (GRCm38) critical splice acceptor site probably null
R3688:Map4k4 UTSW 1 39,985,171 (GRCm38) splice site probably null
R4075:Map4k4 UTSW 1 40,023,462 (GRCm38) missense probably damaging 0.96
R4304:Map4k4 UTSW 1 39,973,972 (GRCm38) missense possibly damaging 0.74
R4564:Map4k4 UTSW 1 39,988,975 (GRCm38) missense probably damaging 1.00
R4569:Map4k4 UTSW 1 40,000,538 (GRCm38) missense probably damaging 1.00
R4613:Map4k4 UTSW 1 40,017,191 (GRCm38) missense probably benign 0.05
R4715:Map4k4 UTSW 1 40,019,564 (GRCm38) missense probably damaging 1.00
R4788:Map4k4 UTSW 1 40,003,916 (GRCm38) missense probably benign 0.01
R4926:Map4k4 UTSW 1 40,017,225 (GRCm38) missense probably damaging 1.00
R4943:Map4k4 UTSW 1 40,019,594 (GRCm38) missense probably damaging 0.99
R5033:Map4k4 UTSW 1 40,007,502 (GRCm38) missense probably damaging 0.99
R5177:Map4k4 UTSW 1 39,986,762 (GRCm38) missense probably damaging 1.00
R5297:Map4k4 UTSW 1 39,962,217 (GRCm38) missense probably damaging 1.00
R5844:Map4k4 UTSW 1 39,999,876 (GRCm38) splice site probably benign
R5952:Map4k4 UTSW 1 39,999,922 (GRCm38) unclassified probably benign
R6111:Map4k4 UTSW 1 40,011,662 (GRCm38) missense probably benign 0.00
R6125:Map4k4 UTSW 1 40,003,965 (GRCm38) missense possibly damaging 0.77
R6838:Map4k4 UTSW 1 39,976,722 (GRCm38) missense probably damaging 1.00
R6927:Map4k4 UTSW 1 40,011,682 (GRCm38) missense probably benign 0.00
R7008:Map4k4 UTSW 1 39,988,971 (GRCm38) missense probably benign 0.44
R7164:Map4k4 UTSW 1 39,973,972 (GRCm38) missense possibly damaging 0.74
R7195:Map4k4 UTSW 1 40,019,669 (GRCm38) missense possibly damaging 0.93
R7589:Map4k4 UTSW 1 40,021,091 (GRCm38) nonsense probably null
R7816:Map4k4 UTSW 1 40,014,208 (GRCm38) missense possibly damaging 0.53
R7869:Map4k4 UTSW 1 39,974,044 (GRCm38) missense unknown
R8013:Map4k4 UTSW 1 39,962,212 (GRCm38) missense unknown
R8145:Map4k4 UTSW 1 40,000,534 (GRCm38) missense
R8154:Map4k4 UTSW 1 40,021,142 (GRCm38) nonsense probably null
R8254:Map4k4 UTSW 1 40,006,675 (GRCm38) missense probably damaging 0.99
R8266:Map4k4 UTSW 1 40,011,653 (GRCm38) missense possibly damaging 0.53
R8375:Map4k4 UTSW 1 40,024,641 (GRCm38) missense possibly damaging 0.73
R8487:Map4k4 UTSW 1 39,988,976 (GRCm38) missense probably damaging 1.00
R8699:Map4k4 UTSW 1 39,976,750 (GRCm38) missense unknown
R8726:Map4k4 UTSW 1 40,003,982 (GRCm38) missense possibly damaging 0.95
R8907:Map4k4 UTSW 1 40,019,610 (GRCm38) missense probably damaging 0.97
R8956:Map4k4 UTSW 1 40,000,680 (GRCm38) missense probably benign 0.11
R8963:Map4k4 UTSW 1 40,000,580 (GRCm38) missense probably damaging 1.00
R9091:Map4k4 UTSW 1 40,003,763 (GRCm38) missense probably benign 0.02
R9234:Map4k4 UTSW 1 39,990,101 (GRCm38) missense unknown
R9270:Map4k4 UTSW 1 40,003,763 (GRCm38) missense probably benign 0.02
R9438:Map4k4 UTSW 1 40,006,792 (GRCm38) missense probably damaging 0.99
R9689:Map4k4 UTSW 1 40,019,562 (GRCm38) missense possibly damaging 0.95
R9771:Map4k4 UTSW 1 39,986,717 (GRCm38) missense unknown
Predicted Primers PCR Primer
(F):5'- CGTTGTTCTATTATGAGCATGCAC -3'
(R):5'- TGTGGCCAAAGATGACATCAC -3'

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