Incidental Mutation 'R1615:Map4k4'
ID 177025
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 039652-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1615 (G1)
Quality Score 225
Status Validated
Chromosome 1
Chromosomal Location 39940073-40065470 bp(+) (GRCm39)
Type of Mutation splice site
DNA Base Change (assembly) A to G at 40045990 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000141400 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000163854] [ENSMUST00000168431] [ENSMUST00000191964] [ENSMUST00000192509] [ENSMUST00000193682] [ENSMUST00000195636] [ENSMUST00000195259] [ENSMUST00000195860]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000163854
SMART Domains Protein: ENSMUSP00000126961
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 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 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 probably benign
Transcript: ENSMUST00000192509
SMART Domains Protein: ENSMUSP00000141665
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: 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
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: 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: ENSMUST00000195860
SMART Domains Protein: ENSMUSP00000141400
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 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 0.0898 question?
Coding Region Coverage
  • 1x: 99.0%
  • 3x: 98.0%
  • 10x: 95.3%
  • 20x: 88.8%
Validation Efficiency 98% (64/65)
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: 55 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adcy8 A T 15: 64,743,625 (GRCm39) C328S probably benign Het
Adgrv1 G T 13: 81,572,407 (GRCm39) T4918K probably benign Het
Aen T C 7: 78,555,660 (GRCm39) Y108H probably damaging Het
Amer3 T C 1: 34,627,252 (GRCm39) M497T probably damaging Het
Arid2 C T 15: 96,269,535 (GRCm39) T1216M possibly damaging Het
Birc6 A G 17: 74,916,404 (GRCm39) probably null Het
Bzw2 A G 12: 36,169,126 (GRCm39) probably benign Het
Ccr1 T C 9: 123,763,573 (GRCm39) H319R probably benign Het
Dnah11 A G 12: 118,014,457 (GRCm39) I2010T probably damaging Het
Dnhd1 A G 7: 105,352,413 (GRCm39) Y2522C probably benign Het
Dnhd1 T A 7: 105,362,913 (GRCm39) I3825K possibly damaging Het
Dst A T 1: 34,238,452 (GRCm39) D3718V probably damaging Het
Esp36 A G 17: 38,730,330 (GRCm39) probably benign Het
Fbxw21 T C 9: 108,972,794 (GRCm39) Y380C probably damaging Het
Fhad1 G A 4: 141,649,634 (GRCm39) T836M probably damaging Het
Fhod1 C T 8: 106,074,463 (GRCm39) probably benign Het
Flt1 A G 5: 147,576,098 (GRCm39) C637R probably damaging Het
Fmnl2 A G 2: 53,008,436 (GRCm39) K809E probably damaging Het
Grm1 G T 10: 10,617,252 (GRCm39) Y510* probably null Het
Hey1 A T 3: 8,729,898 (GRCm39) H186Q possibly damaging Het
Insyn1 C T 9: 58,406,351 (GRCm39) A87V probably damaging Het
Itga2b C T 11: 102,350,963 (GRCm39) probably null Het
Kcnv1 G A 15: 44,977,840 (GRCm39) T66M probably damaging Het
Lmcd1 A G 6: 112,250,911 (GRCm39) D7G probably benign Het
Lrrc1 T C 9: 77,342,400 (GRCm39) D358G possibly damaging Het
Lyn A G 4: 3,748,765 (GRCm39) K248E probably benign Het
Map4k5 A T 12: 69,891,187 (GRCm39) L160H probably damaging Het
Mtcl2 T G 2: 156,862,663 (GRCm39) H1422P probably damaging Het
Myo6 C T 9: 80,215,007 (GRCm39) R1247C probably damaging Het
Myo9a A G 9: 59,695,739 (GRCm39) E347G possibly damaging Het
Ndfip1 C T 18: 38,593,672 (GRCm39) P213S probably benign Het
Neurl3 T C 1: 36,308,470 (GRCm39) E114G possibly damaging Het
Nlrp14 A T 7: 106,795,370 (GRCm39) I877F probably benign Het
Obscn A G 11: 58,990,651 (GRCm39) S1733P probably benign Het
Oxgr1 A T 14: 120,260,185 (GRCm39) S7R probably benign Het
Plcb1 A T 2: 135,204,364 (GRCm39) probably benign Het
Prkag2 G T 5: 25,080,176 (GRCm39) N120K possibly damaging Het
Rnf43 C T 11: 87,622,485 (GRCm39) R529* probably null Het
Saraf A G 8: 34,632,442 (GRCm39) K174E possibly damaging Het
Scrib T C 15: 75,938,054 (GRCm39) Q264R probably benign Het
Sh3rf3 T A 10: 58,966,899 (GRCm39) M747K probably benign Het
Shf T C 2: 122,179,913 (GRCm39) H421R probably damaging Het
Slc35g3 A G 11: 69,651,368 (GRCm39) S228P probably damaging Het
Slit1 A G 19: 41,639,110 (GRCm39) probably benign Het
Srrm4 A G 5: 116,585,359 (GRCm39) probably benign Het
Stfa1 T G 16: 36,100,829 (GRCm39) V23G probably damaging Het
Swap70 A G 7: 109,872,498 (GRCm39) D371G probably benign Het
Tada2a T C 11: 83,993,926 (GRCm39) D186G probably damaging Het
Tdpoz3 C A 3: 93,733,618 (GRCm39) Q98K probably benign Het
Tgfbrap1 A G 1: 43,091,145 (GRCm39) V660A probably benign Het
Tnn A G 1: 159,945,978 (GRCm39) Y947H possibly damaging Het
Trim60 A T 8: 65,453,162 (GRCm39) C362* probably null Het
Vmn1r81 T A 7: 11,994,441 (GRCm39) N56Y probably damaging Het
Vsig8 A G 1: 172,387,280 (GRCm39) D52G probably damaging Het
Wdfy4 G A 14: 32,764,469 (GRCm39) R2140C 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
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'- AGTATTGAGCCCCGGCTTCTTTG -3'
(R):5'- TGATGCTGGTACGTTCAGGAGAGAC -3'

Sequencing Primer
(F):5'- TCTTTGGGAGAGAGTGGAAAAGC -3'
(R):5'- aggcaaagcatttaattccactc -3'
Posted On 2014-04-24