Incidental Mutation 'R0674:Map4k4'
ID 61549
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 038859-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R0674 (G1)
Quality Score 100
Status Validated
Chromosome 1
Chromosomal Location 39940073-40065470 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 40042975 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Leucine at position 118 (H118L)
Ref Sequence ENSEMBL: ENSMUSP00000141235 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000163854] [ENSMUST00000168431] [ENSMUST00000191964] [ENSMUST00000192509] [ENSMUST00000195860] [ENSMUST00000195259] [ENSMUST00000195636] [ENSMUST00000193682]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000163854
AA Change: H610L

PolyPhen 2 Score 0.435 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: H610L

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 probably benign
Transcript: ENSMUST00000168431
SMART Domains Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074

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: ENSMUST00000191865
Predicted Effect probably damaging
Transcript: ENSMUST00000191964
AA Change: H118L

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000141235
Gene: ENSMUSG00000026074
AA Change: H118L

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 unknown
Transcript: ENSMUST00000192355
AA Change: H120L
Predicted Effect unknown
Transcript: ENSMUST00000192509
AA Change: H556L
SMART Domains Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: H556L

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 possibly damaging
Transcript: ENSMUST00000195860
AA Change: H610L

PolyPhen 2 Score 0.568 (Sensitivity: 0.88; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: H610L

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 noncoding transcript
Transcript: ENSMUST00000195356
Predicted Effect probably benign
Transcript: ENSMUST00000195259
SMART Domains Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074

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 benign
Transcript: ENSMUST00000195636
SMART Domains Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074

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 benign
Transcript: ENSMUST00000193682
SMART Domains Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074

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
Meta Mutation Damage Score 0.0736 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.4%
  • 10x: 96.3%
  • 20x: 90.4%
Validation Efficiency 97% (124/128)
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: 62 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adar A G 3: 89,657,130 (GRCm39) probably benign Het
Adgrl2 A T 3: 148,543,315 (GRCm39) M803K possibly damaging Het
Atp13a5 T C 16: 29,067,102 (GRCm39) probably benign Het
Atp2a3 T C 11: 72,872,711 (GRCm39) I753T probably damaging Het
Bace2 G A 16: 97,237,949 (GRCm39) V467M possibly damaging Het
Bltp1 T A 3: 37,098,775 (GRCm39) V1134E possibly damaging Het
Ccser2 A G 14: 36,640,548 (GRCm39) C11R possibly damaging Het
Cd2ap T A 17: 43,156,283 (GRCm39) I85F possibly damaging Het
Cd2bp2 C T 7: 126,794,008 (GRCm39) E94K probably damaging Het
Chrna3 C A 9: 54,922,456 (GRCm39) A451S probably damaging Het
Cmya5 C A 13: 93,229,299 (GRCm39) V1930F probably damaging Het
Csmd1 T C 8: 16,050,550 (GRCm39) T2229A probably benign Het
Csrnp2 A T 15: 100,385,872 (GRCm39) L122H probably damaging Het
Cyp11b2 G A 15: 74,727,393 (GRCm39) P96L probably damaging Het
Ddr1 G T 17: 36,000,561 (GRCm39) S368* probably null Het
E2f1 T C 2: 154,406,029 (GRCm39) K115E probably damaging Het
Erlec1 A T 11: 30,885,073 (GRCm39) probably benign Het
Fus T A 7: 127,571,948 (GRCm39) probably benign Het
Gml G A 15: 74,685,709 (GRCm39) T92I probably damaging Het
Herc1 T C 9: 66,408,474 (GRCm39) S4567P probably damaging Het
Iglc2 A G 16: 19,017,591 (GRCm39) S5P probably benign Het
Itgam T C 7: 127,715,390 (GRCm39) V1028A possibly damaging Het
Krt222 T A 11: 99,127,086 (GRCm39) N178I probably benign Het
Krt81 C A 15: 101,361,508 (GRCm39) R24L possibly damaging Het
Luzp1 C T 4: 136,270,768 (GRCm39) T997I possibly damaging Het
Maml1 G T 11: 50,148,885 (GRCm39) Q952K probably benign Het
Map2 A G 1: 66,452,361 (GRCm39) E499G probably damaging Het
Myzap T C 9: 71,422,426 (GRCm39) D382G probably damaging Het
Naip5 T C 13: 100,359,707 (GRCm39) T510A probably benign Het
Nek6 G C 2: 38,448,916 (GRCm39) G95R possibly damaging Het
Nphp3 T C 9: 103,913,481 (GRCm39) probably null Het
Nr1d2 T C 14: 18,215,086 (GRCm38) S309G probably benign Het
Nrcam A T 12: 44,611,105 (GRCm39) I570F probably benign Het
Oas1d T C 5: 121,058,049 (GRCm39) I331T probably benign Het
Or2h2c G C 17: 37,422,347 (GRCm39) L176V probably benign Het
Or4f14 A T 2: 111,743,018 (GRCm39) F86I probably benign Het
Or51b6 T C 7: 103,556,462 (GRCm39) V272A probably benign Het
Pex5l A T 3: 33,006,765 (GRCm39) W535R probably damaging Het
Pisd C T 5: 32,931,781 (GRCm39) R202H probably benign Het
Plxna2 A G 1: 194,331,783 (GRCm39) N403S probably benign Het
Prdm12 A G 2: 31,533,924 (GRCm39) I180M probably benign Het
Prpf6 A G 2: 181,273,767 (GRCm39) T304A probably benign Het
Ptprm G A 17: 67,498,336 (GRCm39) T35I possibly damaging Het
Ptx3 T A 3: 66,132,148 (GRCm39) I223N probably damaging Het
Pygb G A 2: 150,657,054 (GRCm39) probably null Het
Qrsl1 A G 10: 43,771,997 (GRCm39) probably benign Het
Rad51ap2 T C 12: 11,508,818 (GRCm39) probably null Het
Ralbp1 C T 17: 66,159,748 (GRCm39) R505H probably benign Het
Rimbp3 T C 16: 17,030,601 (GRCm39) S1342P probably benign Het
Slc22a14 C A 9: 119,007,608 (GRCm39) R267L probably damaging Het
Slco6c1 T A 1: 97,032,498 (GRCm39) probably benign Het
Tcp1 T C 17: 13,142,131 (GRCm39) I375T probably damaging Het
Tiparp T C 3: 65,460,586 (GRCm39) I525T probably benign Het
Tjp2 A G 19: 24,108,680 (GRCm39) L144P probably benign Het
Tssk2 A G 16: 17,716,930 (GRCm39) D111G probably benign Het
Ttn T C 2: 76,775,823 (GRCm39) T1740A possibly damaging Het
Vmn2r102 T A 17: 19,898,129 (GRCm39) D381E probably benign Het
Vsig10 C T 5: 117,481,911 (GRCm39) T367M probably damaging Het
Wnt11 T C 7: 98,495,735 (GRCm39) C80R probably damaging Het
Zar1 T A 5: 72,737,643 (GRCm39) probably null Het
Zfp52 A T 17: 21,782,108 (GRCm39) H652L probably damaging Het
Zpr1 T A 9: 46,186,747 (GRCm39) L194Q 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
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'- CTATTGGCTGCTCCATGCTTGACAC -3'
(R):5'- AAAGAGAAAACAGCGCGTCTGTCTG -3'

Sequencing Primer
(F):5'- GCTCCATGCTTGACACTATGC -3'
(R):5'- TGTCCTTACCCTTGGAGGC -3'
Posted On 2013-07-30