Incidental Mutation 'R0496:Map4k4'
ID 43896
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 038692-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R0496 (G1)
Quality Score 141
Status Validated
Chromosome 1
Chromosomal Location 39940073-40065470 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 40045982 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Threonine at position 754 (S754T)
Ref Sequence ENSEMBL: ENSMUSP00000141400 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000163854] [ENSMUST00000168431] [ENSMUST00000191964] [ENSMUST00000192509] [ENSMUST00000195259] [ENSMUST00000195636] [ENSMUST00000193682] [ENSMUST00000195860]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000163854
AA Change: S754T

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: S754T

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 unknown
Transcript: ENSMUST00000168431
AA Change: S707T
SMART Domains Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: S707T

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: ENSMUST00000191865
AA Change: S111T
Predicted Effect probably benign
Transcript: ENSMUST00000191964
SMART Domains Protein: ENSMUSP00000141235
Gene: ENSMUSG00000026074

DomainStartEndE-ValueType
low complexity region 4 28 N/A INTRINSIC
SCOP:d1i7qa_ 35 139 7e-3 SMART
low complexity region 195 206 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000192194
Predicted Effect probably benign
Transcript: ENSMUST00000192355
Predicted Effect unknown
Transcript: ENSMUST00000192509
AA Change: S700T
SMART Domains Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: S700T

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: ENSMUST00000195259
AA Change: S677T
SMART Domains Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: S677T

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 unknown
Transcript: ENSMUST00000195636
AA Change: S677T
SMART Domains Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: S677T

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 probably damaging
Transcript: ENSMUST00000193682
AA Change: S623T

PolyPhen 2 Score 0.985 (Sensitivity: 0.74; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: S623T

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: ENSMUST00000195860
AA Change: S754T

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: S754T

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
Meta Mutation Damage Score 0.1633 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.3%
  • 10x: 96.3%
  • 20x: 92.6%
Validation Efficiency 98% (99/101)
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: 97 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110002E22Rik A G 3: 137,774,005 (GRCm39) K1065E probably damaging Het
4933402N03Rik T C 7: 130,747,860 (GRCm39) N44S probably benign Het
Abca13 A G 11: 9,241,701 (GRCm39) D1188G probably benign Het
Abcb11 C T 2: 69,108,228 (GRCm39) probably benign Het
Abcc8 A T 7: 45,758,244 (GRCm39) I1274N probably damaging Het
Adamtsl1 G A 4: 86,259,435 (GRCm39) C827Y probably damaging Het
Agap3 T A 5: 24,706,241 (GRCm39) V369E probably damaging Het
Ankrd13b G A 11: 77,363,867 (GRCm39) R195C probably damaging Het
Ap3b1 A G 13: 94,609,446 (GRCm39) probably benign Het
Arhgef40 A T 14: 52,242,364 (GRCm39) probably benign Het
Atad5 A G 11: 79,991,182 (GRCm39) I692V probably benign Het
Atp5f1b G T 10: 127,922,043 (GRCm39) R310L possibly damaging Het
AY358078 A T 14: 52,040,989 (GRCm39) M103L unknown Het
Bcl9l T G 9: 44,420,815 (GRCm39) V1370G probably benign Het
Bglap3 T A 3: 88,276,444 (GRCm39) Q38L probably damaging Het
Bltp1 A G 3: 37,041,784 (GRCm39) T2721A probably damaging Het
Ccn2 G T 10: 24,473,413 (GRCm39) M317I possibly damaging Het
Cd38 T C 5: 44,026,233 (GRCm39) F6L probably damaging Het
Cela3a A C 4: 137,131,779 (GRCm39) V138G probably damaging Het
Cemip2 A T 19: 21,774,709 (GRCm39) N117I possibly damaging Het
Clvs1 T A 4: 9,424,241 (GRCm39) I229N probably damaging Het
Cpne1 G A 2: 155,921,339 (GRCm39) H16Y probably damaging Het
Ctc1 T C 11: 68,926,333 (GRCm39) L1069P probably damaging Het
Dgkd G A 1: 87,864,622 (GRCm39) S996N probably null Het
Dnah9 A T 11: 65,965,961 (GRCm39) M1685K probably null Het
Dnajb12 C T 10: 59,715,623 (GRCm39) R42* probably null Het
Dock5 T C 14: 68,054,967 (GRCm39) Q633R probably damaging Het
Dync2h1 A G 9: 7,155,180 (GRCm39) M868T probably benign Het
Enpp1 G T 10: 24,547,950 (GRCm39) H208Q probably benign Het
Epha7 T A 4: 28,821,292 (GRCm39) D152E probably damaging Het
Fancd2 T C 6: 113,532,091 (GRCm39) probably benign Het
Gart G A 16: 91,419,925 (GRCm39) probably benign Het
Gm10964 A T 3: 103,646,745 (GRCm39) probably null Het
Gpbar1 T C 1: 74,318,140 (GRCm39) F128L probably benign Het
Gsx2 T A 5: 75,237,726 (GRCm39) M226K probably benign Het
Gucd1 T C 10: 75,347,100 (GRCm39) D50G possibly damaging Het
Has1 A G 17: 18,064,008 (GRCm39) Y544H probably benign Het
Hc A T 2: 34,903,583 (GRCm39) Y1024N probably damaging Het
Hoxa13 CCG CCGCG 6: 52,237,618 (GRCm39) probably null Het
Ift122 T A 6: 115,882,863 (GRCm39) H659Q probably benign Het
Itga2 T C 13: 114,990,435 (GRCm39) Q902R probably benign Het
Itgb2l T C 16: 96,235,901 (GRCm39) K181E possibly damaging Het
Jak3 A T 8: 72,135,041 (GRCm39) H558L probably damaging Het
Kcnh8 A G 17: 53,032,886 (GRCm39) T58A probably benign Het
Klhl6 GT G 16: 19,775,716 (GRCm39) 279 probably null Het
Krt33a C T 11: 99,903,155 (GRCm39) probably benign Het
Magi2 A T 5: 20,866,357 (GRCm39) probably benign Het
Map4 G A 9: 109,868,918 (GRCm39) probably benign Het
Mapk8ip3 A G 17: 25,133,424 (GRCm39) probably benign Het
Mib1 A G 18: 10,804,773 (GRCm39) S918G probably benign Het
Mipol1 T A 12: 57,503,963 (GRCm39) V377D probably damaging Het
Mlh1 T C 9: 111,070,624 (GRCm39) T364A probably benign Het
Mta1 C T 12: 113,094,941 (GRCm39) Q400* probably null Het
Mthfd1l C G 10: 4,040,006 (GRCm39) R806G probably benign Het
Myh13 C A 11: 67,239,641 (GRCm39) N730K probably damaging Het
Myom1 A G 17: 71,391,301 (GRCm39) K937E probably damaging Het
Naxd T C 8: 11,560,224 (GRCm39) probably benign Het
Negr1 G T 3: 156,721,904 (GRCm39) K159N probably damaging Het
Nwd2 G T 5: 63,963,686 (GRCm39) W1090L probably damaging Het
Or1e1f T C 11: 73,855,706 (GRCm39) S91P probably benign Het
Or2j3 A G 17: 38,615,549 (GRCm39) S268P probably damaging Het
Or51v14 C T 7: 103,261,204 (GRCm39) A119T probably benign Het
Or52r1c T C 7: 102,734,797 (GRCm39) I19T probably damaging Het
Or5d41 A T 2: 88,054,499 (GRCm39) Y292* probably null Het
Pcsk6 G A 7: 65,576,997 (GRCm39) S58N probably benign Het
Pdzrn3 G A 6: 101,127,531 (GRCm39) T1045I possibly damaging Het
Pitrm1 T C 13: 6,618,750 (GRCm39) L641P probably damaging Het
Pkd1l1 G T 11: 8,879,430 (GRCm39) H474N probably damaging Het
Pltp A G 2: 164,694,381 (GRCm39) probably benign Het
Qtrt1 C T 9: 21,330,844 (GRCm39) T324M probably benign Het
Racgap1 A T 15: 99,537,713 (GRCm39) probably benign Het
Rhbg A G 3: 88,161,805 (GRCm39) V50A probably benign Het
Rnf135 G A 11: 80,074,776 (GRCm39) V12M probably damaging Het
Rnf7l G T 10: 63,257,381 (GRCm39) C46* probably null Het
Rufy2 T C 10: 62,828,949 (GRCm39) V117A probably damaging Het
Safb A G 17: 56,912,630 (GRCm39) M866V probably benign Het
Slc35c2 G T 2: 165,122,735 (GRCm39) T183K probably damaging Het
Slc39a7 A G 17: 34,248,512 (GRCm39) L377P probably damaging Het
Slit1 G A 19: 41,596,750 (GRCm39) probably benign Het
Spaca9 G A 2: 28,583,022 (GRCm39) H133Y probably damaging Het
Spout1 A G 2: 30,064,983 (GRCm39) F339S probably benign Het
St6gal2 A G 17: 55,789,015 (GRCm39) I16M probably damaging Het
Stat2 T C 10: 128,112,378 (GRCm39) M6T probably benign Het
Swt1 T A 1: 151,287,021 (GRCm39) H157L probably benign Het
Syne2 A G 12: 76,085,714 (GRCm39) N147D possibly damaging Het
Tmem222 A T 4: 133,004,902 (GRCm39) M45K possibly damaging Het
Tmem30a T A 9: 79,684,567 (GRCm39) H95L probably damaging Het
Tns3 A C 11: 8,497,262 (GRCm39) probably benign Het
Trpm3 A G 19: 22,676,142 (GRCm39) I103V probably benign Het
Ube2n T C 10: 95,377,206 (GRCm39) F57S probably benign Het
Vil1 T C 1: 74,460,499 (GRCm39) S219P possibly damaging Het
Wdfy4 A G 14: 32,862,695 (GRCm39) probably benign Het
Wdr7 T C 18: 63,924,914 (GRCm39) S966P probably benign Het
Wnt8a A G 18: 34,677,900 (GRCm39) N103D probably damaging Het
Zfp523 G A 17: 28,419,419 (GRCm39) E186K possibly damaging Het
Zfp791 A T 8: 85,836,609 (GRCm39) D418E probably benign Het
Zscan20 A G 4: 128,485,682 (GRCm39) V192A probably benign Het
Other mutations in Map4k4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00328:Map4k4 APN 1 40,043,976 (GRCm39) missense probably damaging 0.99
IGL00417:Map4k4 APN 1 40,053,692 (GRCm39) missense possibly damaging 0.92
IGL00516:Map4k4 APN 1 40,053,762 (GRCm39) missense probably damaging 1.00
IGL01545:Map4k4 APN 1 40,053,389 (GRCm39) splice site probably benign
IGL02092:Map4k4 APN 1 40,063,508 (GRCm39) missense probably damaging 1.00
IGL02092:Map4k4 APN 1 40,025,943 (GRCm39) missense probably benign 0.12
IGL02570:Map4k4 APN 1 40,019,739 (GRCm39) missense probably benign 0.06
IGL02626:Map4k4 APN 1 40,053,257 (GRCm39) splice site probably benign
IGL02993:Map4k4 APN 1 40,053,348 (GRCm39) missense probably damaging 0.98
IGL03178:Map4k4 APN 1 40,025,853 (GRCm39) missense possibly damaging 0.63
tank UTSW 1 40,044,024 (GRCm39) missense possibly damaging 0.93
IGL02835:Map4k4 UTSW 1 40,049,760 (GRCm39) missense probably damaging 0.99
R0498:Map4k4 UTSW 1 40,029,338 (GRCm39) missense probably benign 0.22
R0588:Map4k4 UTSW 1 40,044,024 (GRCm39) missense possibly damaging 0.93
R0674:Map4k4 UTSW 1 40,042,975 (GRCm39) missense probably damaging 1.00
R1205:Map4k4 UTSW 1 40,043,004 (GRCm39) missense probably damaging 1.00
R1349:Map4k4 UTSW 1 40,060,319 (GRCm39) missense probably damaging 1.00
R1615:Map4k4 UTSW 1 40,045,990 (GRCm39) splice site probably benign
R1763:Map4k4 UTSW 1 40,039,917 (GRCm39) splice site probably benign
R1800:Map4k4 UTSW 1 40,062,620 (GRCm39) missense probably damaging 1.00
R1893:Map4k4 UTSW 1 40,040,717 (GRCm39) missense probably benign 0.08
R2411:Map4k4 UTSW 1 40,046,656 (GRCm39) missense probably damaging 0.96
R2851:Map4k4 UTSW 1 40,039,915 (GRCm39) splice site probably benign
R2852:Map4k4 UTSW 1 40,039,915 (GRCm39) splice site probably benign
R2987:Map4k4 UTSW 1 40,025,925 (GRCm39) missense probably damaging 1.00
R3087:Map4k4 UTSW 1 40,060,242 (GRCm39) critical splice acceptor site probably null
R3688:Map4k4 UTSW 1 40,024,331 (GRCm39) splice site probably null
R4075:Map4k4 UTSW 1 40,062,622 (GRCm39) missense probably damaging 0.96
R4304:Map4k4 UTSW 1 40,013,132 (GRCm39) missense possibly damaging 0.74
R4564:Map4k4 UTSW 1 40,028,135 (GRCm39) missense probably damaging 1.00
R4569:Map4k4 UTSW 1 40,039,698 (GRCm39) missense probably damaging 1.00
R4613:Map4k4 UTSW 1 40,056,351 (GRCm39) missense probably benign 0.05
R4715:Map4k4 UTSW 1 40,058,724 (GRCm39) missense probably damaging 1.00
R4788:Map4k4 UTSW 1 40,043,076 (GRCm39) missense probably benign 0.01
R4926:Map4k4 UTSW 1 40,056,385 (GRCm39) missense probably damaging 1.00
R4943:Map4k4 UTSW 1 40,058,754 (GRCm39) missense probably damaging 0.99
R5033:Map4k4 UTSW 1 40,046,662 (GRCm39) missense probably damaging 0.99
R5177:Map4k4 UTSW 1 40,025,922 (GRCm39) missense probably damaging 1.00
R5297:Map4k4 UTSW 1 40,001,377 (GRCm39) missense probably damaging 1.00
R5844:Map4k4 UTSW 1 40,039,036 (GRCm39) splice site probably benign
R5952:Map4k4 UTSW 1 40,039,082 (GRCm39) unclassified probably benign
R6111:Map4k4 UTSW 1 40,050,822 (GRCm39) missense probably benign 0.00
R6125:Map4k4 UTSW 1 40,043,125 (GRCm39) missense possibly damaging 0.77
R6838:Map4k4 UTSW 1 40,015,882 (GRCm39) missense probably damaging 1.00
R6927:Map4k4 UTSW 1 40,050,842 (GRCm39) missense probably benign 0.00
R7008:Map4k4 UTSW 1 40,028,131 (GRCm39) missense probably benign 0.44
R7164:Map4k4 UTSW 1 40,013,132 (GRCm39) missense possibly damaging 0.74
R7195:Map4k4 UTSW 1 40,058,829 (GRCm39) missense possibly damaging 0.93
R7352:Map4k4 UTSW 1 40,001,387 (GRCm39) missense unknown
R7589:Map4k4 UTSW 1 40,060,251 (GRCm39) nonsense probably null
R7816:Map4k4 UTSW 1 40,053,368 (GRCm39) missense possibly damaging 0.53
R7869:Map4k4 UTSW 1 40,013,204 (GRCm39) missense unknown
R8013:Map4k4 UTSW 1 40,001,372 (GRCm39) missense unknown
R8145:Map4k4 UTSW 1 40,039,694 (GRCm39) missense
R8154:Map4k4 UTSW 1 40,060,302 (GRCm39) nonsense probably null
R8254:Map4k4 UTSW 1 40,045,835 (GRCm39) missense probably damaging 0.99
R8266:Map4k4 UTSW 1 40,050,813 (GRCm39) missense possibly damaging 0.53
R8375:Map4k4 UTSW 1 40,063,801 (GRCm39) missense possibly damaging 0.73
R8487:Map4k4 UTSW 1 40,028,136 (GRCm39) missense probably damaging 1.00
R8699:Map4k4 UTSW 1 40,015,910 (GRCm39) missense unknown
R8726:Map4k4 UTSW 1 40,043,142 (GRCm39) missense possibly damaging 0.95
R8907:Map4k4 UTSW 1 40,058,770 (GRCm39) missense probably damaging 0.97
R8956:Map4k4 UTSW 1 40,039,840 (GRCm39) missense probably benign 0.11
R8963:Map4k4 UTSW 1 40,039,740 (GRCm39) missense probably damaging 1.00
R9091:Map4k4 UTSW 1 40,042,923 (GRCm39) missense probably benign 0.02
R9234:Map4k4 UTSW 1 40,029,261 (GRCm39) missense unknown
R9270:Map4k4 UTSW 1 40,042,923 (GRCm39) missense probably benign 0.02
R9438:Map4k4 UTSW 1 40,045,952 (GRCm39) missense probably damaging 0.99
R9689:Map4k4 UTSW 1 40,058,722 (GRCm39) missense possibly damaging 0.95
R9771:Map4k4 UTSW 1 40,025,877 (GRCm39) missense unknown
Predicted Primers PCR Primer
(F):5'- AGTATTGAGCCCCGGCTTCTTTGG -3'
(R):5'- TGATGCTGGTACGTTCAGGAGAGAC -3'

Sequencing Primer
(F):5'- TCTTTGGGAGAGAGTGGAAAAGC -3'
(R):5'- aggcaaagcatttaattccactc -3'
Posted On 2013-05-29