Incidental Mutation 'R4564:Map4k4'
ID 343217
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 041789-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4564 (G1)
Quality Score 218
Status Validated
Chromosome 1
Chromosomal Location 39940073-40065470 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 40028135 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 319 (T319A)
Ref Sequence ENSEMBL: ENSMUSP00000142056 (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: T319A
SMART Domains Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: T319A

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: T319A
SMART Domains Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: T319A

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 probably benign
Transcript: ENSMUST00000191761
AA Change: T319A

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
SMART Domains Protein: ENSMUSP00000141332
Gene: ENSMUSG00000026074
AA Change: T319A

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 possibly damaging
Transcript: ENSMUST00000192509
AA Change: T319A

PolyPhen 2 Score 0.466 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: T319A

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: T319A
SMART Domains Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: T319A

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: T319A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: T319A

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 possibly damaging
Transcript: ENSMUST00000195636
AA Change: T319A

PolyPhen 2 Score 0.466 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: T319A

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: T319A
SMART Domains Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: T319A

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 0.1394 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.5%
  • 10x: 97.0%
  • 20x: 94.6%
Validation Efficiency 97% (58/60)
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: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Atad3a C T 4: 155,831,766 (GRCm39) probably null Het
Bach2 T G 4: 32,563,338 (GRCm39) S602A probably damaging Het
Ccl19 G T 4: 42,756,295 (GRCm39) S12R probably damaging Het
Cfap54 T C 10: 92,675,402 (GRCm39) probably benign Het
Cndp1 T A 18: 84,640,411 (GRCm39) I265F probably damaging Het
Cnot3 G A 7: 3,656,257 (GRCm39) R181H probably damaging Het
Dicer1 T A 12: 104,671,010 (GRCm39) K1011* probably null Het
Dip2b G A 15: 100,055,139 (GRCm39) W99* probably null Het
Fpr-rs6 A T 17: 20,403,168 (GRCm39) Y64* probably null Het
Fubp1 C A 3: 151,928,573 (GRCm39) Y480* probably null Het
Gfra1 T C 19: 58,227,682 (GRCm39) probably null Het
Gm10770 T C 2: 150,020,831 (GRCm39) T229A probably benign Het
Gm826 A C 2: 160,153,913 (GRCm39) probably benign Het
Gpd2 G A 2: 57,197,095 (GRCm39) V217I possibly damaging Het
Hectd4 T C 5: 121,488,494 (GRCm39) I3595T probably benign Het
Lmln A G 16: 32,930,226 (GRCm39) E561G probably benign Het
Lrrc71 T A 3: 87,652,715 (GRCm39) probably benign Het
Man2a2 T A 7: 80,018,586 (GRCm39) Y91F probably benign Het
Mcm6 G T 1: 128,271,196 (GRCm39) H474Q probably damaging Het
Mn1 C G 5: 111,568,533 (GRCm39) N834K possibly damaging Het
Mslnl G A 17: 25,961,908 (GRCm39) V128M probably damaging Het
Niban3 T C 8: 72,057,704 (GRCm39) probably benign Het
Npas2 A G 1: 39,326,647 (GRCm39) D44G probably damaging Het
Npc1 C T 18: 12,324,789 (GRCm39) G1235R probably damaging Het
Olfml2a C T 2: 38,850,306 (GRCm39) T674I probably benign Het
Or4f58 A G 2: 111,852,112 (GRCm39) L29P possibly damaging Het
Pgap6 A G 17: 26,336,837 (GRCm39) R252G possibly damaging Het
Plxnb1 C T 9: 108,942,488 (GRCm39) A1779V probably benign Het
Ppil3 T A 1: 58,470,481 (GRCm39) D123V probably damaging Het
Prr23a3 A G 9: 98,747,190 (GRCm39) E48G probably damaging Het
Prr5l T C 2: 101,577,094 (GRCm39) E110G probably damaging Het
Ptgir A G 7: 16,640,794 (GRCm39) M29V possibly damaging Het
R3hdm1 C T 1: 128,149,396 (GRCm39) T839M probably benign Het
Rasgrf2 G A 13: 92,033,773 (GRCm39) Q544* probably null Het
Riok3 C A 18: 12,281,936 (GRCm39) R302S probably damaging Het
Rnf145 A G 11: 44,439,635 (GRCm39) K144E probably benign Het
Sin3b A C 8: 73,480,209 (GRCm39) T904P probably damaging Het
Skint4 C T 4: 111,977,066 (GRCm39) T152M probably damaging Het
Slc22a2 A G 17: 12,828,943 (GRCm39) I350V probably benign Het
Slc6a11 G T 6: 114,108,323 (GRCm39) G29V probably benign Het
Speg A C 1: 75,368,478 (GRCm39) H676P probably damaging Het
St6gal2 T A 17: 55,789,648 (GRCm39) H227Q probably damaging Het
Strn3 A G 12: 51,680,404 (GRCm39) S399P probably benign Het
Tbc1d1 A G 5: 64,330,827 (GRCm39) E2G probably damaging Het
Tecpr2 T A 12: 110,921,219 (GRCm39) M1264K probably benign Het
Trpm6 T C 19: 18,809,961 (GRCm39) L1119P possibly damaging Het
Upf2 A C 2: 6,032,123 (GRCm39) T890P unknown Het
Upk1b T A 16: 38,600,469 (GRCm39) K170N probably benign Het
Vmn1r78 A T 7: 11,886,485 (GRCm39) Y32F probably damaging Het
Vps11 A G 9: 44,272,894 (GRCm39) F12S probably damaging Het
Zfp318 T A 17: 46,723,741 (GRCm39) C1915S possibly damaging Het
Zfp346 A C 13: 55,261,520 (GRCm39) R103S probably damaging 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
R0496:Map4k4 UTSW 1 40,045,982 (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
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'- GTGGAGAATGACCAGCTCTTC -3'
(R):5'- CAGAGATCTGTCATGGGGTG -3'

Sequencing Primer
(F):5'- AGAATGACCAGCTCTTCTGTAGG -3'
(R):5'- TCTGTCATGGGGTGAGAAAAATG -3'
Posted On 2015-09-24