Incidental Mutation 'R4788:Map4k4'
ID 367215
Institutional Source Beutler Lab
Gene Symbol Map4k4
Ensembl Gene ENSMUSG00000026074
Gene Name mitogen-activated protein kinase kinase kinase kinase 4
Synonyms 9430080K19Rik, Nik
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4788 (G1)
Quality Score 225
Status Not validated
Chromosome 1
Chromosomal Location 39940073-40065470 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 40043076 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 644 (S644P)
Ref Sequence ENSEMBL: ENSMUSP00000141400 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000163854] [ENSMUST00000168431] [ENSMUST00000191964] [ENSMUST00000192509] [ENSMUST00000195860] [ENSMUST00000193682] [ENSMUST00000195636] [ENSMUST00000195259]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000163854
AA Change: S644P

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: S644P

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
AA Change: S152P

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000141235
Gene: ENSMUSG00000026074
AA Change: S152P

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: S154P
Predicted Effect unknown
Transcript: ENSMUST00000192509
AA Change: S590P
SMART Domains Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: S590P

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: ENSMUST00000195860
AA Change: S644P

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)
SMART Domains Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: S644P

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: 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
Coding Region Coverage
  • 1x: 98.8%
  • 3x: 98.4%
  • 10x: 96.9%
  • 20x: 94.4%
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: 68 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca4 G A 3: 121,960,361 (GRCm39) D815N probably damaging Het
Abcc9 A T 6: 142,566,456 (GRCm39) C1135* probably null Het
Ap3b1 G A 13: 94,702,149 (GRCm39) M1067I unknown Het
Arhgap15 T C 2: 43,638,902 (GRCm39) M1T probably null Het
Boc T C 16: 44,320,796 (GRCm39) D288G probably damaging Het
Brsk1 G T 7: 4,701,954 (GRCm39) probably null Het
Cabp1 T C 5: 115,313,530 (GRCm39) N226S probably benign Het
Capn13 A T 17: 73,644,427 (GRCm39) Y367* probably null Het
Ccdc191 A G 16: 43,777,185 (GRCm39) E632G probably damaging Het
Cit T C 5: 116,071,565 (GRCm39) S591P probably damaging Het
Ckmt1 T C 2: 121,190,427 (GRCm39) V118A possibly damaging Het
Cndp2 T C 18: 84,693,289 (GRCm39) N157S probably damaging Het
Col6a3 A G 1: 90,700,672 (GRCm39) probably null Het
Coq2 A T 5: 100,805,775 (GRCm39) V287E probably damaging Het
Cpa6 T C 1: 10,478,502 (GRCm39) K278R possibly damaging Het
Cracdl A T 1: 37,670,556 (GRCm39) I128K probably damaging Het
Cybb C G X: 9,316,989 (GRCm39) D246H probably benign Het
Cyp3a25 A T 5: 145,921,892 (GRCm39) Y347* probably null Het
Dcun1d4 G T 5: 73,691,971 (GRCm39) W160L probably damaging Het
Dennd4c A G 4: 86,738,200 (GRCm39) T994A probably benign Het
Dhx57 T C 17: 80,582,760 (GRCm39) T229A probably benign Het
Dnah6 T A 6: 73,106,513 (GRCm39) R1741S probably damaging Het
Dock1 T A 7: 134,747,213 (GRCm39) V1508D probably damaging Het
Donson T C 16: 91,484,721 (GRCm39) T117A possibly damaging Het
Dtnb A G 12: 3,822,699 (GRCm39) D533G probably damaging Het
Fcrl5 A G 3: 87,364,495 (GRCm39) N470S probably damaging Het
Focad T A 4: 88,275,706 (GRCm39) V1105E unknown Het
Fry T C 5: 150,323,101 (GRCm39) V1084A probably benign Het
Gabra1 G T 11: 42,037,980 (GRCm39) R213S probably damaging Het
Gbp2b A C 3: 142,317,171 (GRCm39) K509T probably benign Het
Gprc6a T C 10: 51,491,104 (GRCm39) T811A probably benign Het
Hmgcs2 A G 3: 98,198,400 (GRCm39) D101G probably damaging Het
Ifna11 G A 4: 88,738,245 (GRCm39) W17* probably null Het
Ighv1-62-3 T A 12: 115,424,672 (GRCm39) M100L probably benign Het
Lgmn T A 12: 102,368,936 (GRCm39) Y181F probably benign Het
Med9 T A 11: 59,839,266 (GRCm39) N58K probably benign Het
Nav1 C T 1: 135,397,461 (GRCm39) A903T probably benign Het
Nop53 T C 7: 15,676,240 (GRCm39) E153G possibly damaging Het
Nop56 G T 2: 130,120,820 (GRCm39) V190L probably benign Het
Nyap2 A T 1: 81,247,112 (GRCm39) M687L probably benign Het
Or4a81 G A 2: 89,619,480 (GRCm39) S72F probably damaging Het
Or8g17 T C 9: 38,930,217 (GRCm39) T207A probably benign Het
Or8g26 A G 9: 39,095,908 (GRCm39) T145A probably benign Het
Osbp2 T C 11: 3,813,320 (GRCm39) K183R probably benign Het
Pappa2 A G 1: 158,611,487 (GRCm39) V1492A possibly damaging Het
Pax1 A G 2: 147,208,124 (GRCm39) Q244R possibly damaging Het
Pcdh9 C A 14: 94,124,851 (GRCm39) V317F probably damaging Het
Pkhd1l1 A T 15: 44,361,417 (GRCm39) Q489L probably damaging Het
Poln A T 5: 34,286,675 (GRCm39) S164R probably benign Het
Ptf1a T C 2: 19,450,762 (GRCm39) S31P probably benign Het
Rasal3 A T 17: 32,618,312 (GRCm39) D164E probably benign Het
Rnf170 A G 8: 26,630,891 (GRCm39) E168G probably damaging Het
Rubcn A G 16: 32,656,778 (GRCm39) probably null Het
Sec16b A T 1: 157,389,094 (GRCm39) T830S possibly damaging Het
Sel1l3 A G 5: 53,289,175 (GRCm39) V882A probably benign Het
Sfpq A G 4: 126,919,791 (GRCm39) E512G probably damaging Het
Sh3pxd2a A G 19: 47,302,518 (GRCm39) L187P probably damaging Het
Skint6 C T 4: 113,095,533 (GRCm39) G42D possibly damaging Het
Slc7a2 A G 8: 41,367,023 (GRCm39) I526V probably benign Het
Spmip7 T C 11: 11,438,652 (GRCm39) probably null Het
Ssh2 A T 11: 77,320,624 (GRCm39) N328Y probably damaging Het
Taok2 G A 7: 126,467,304 (GRCm39) S167L possibly damaging Het
Tom1l2 A G 11: 60,139,844 (GRCm39) L275P probably damaging Het
Trgv5 A G 13: 19,376,724 (GRCm39) K57R probably benign Het
Tyrp1 C T 4: 80,763,180 (GRCm39) R356* probably null Het
Zan A G 5: 137,440,375 (GRCm39) L1953P unknown Het
Zfhx3 T C 8: 109,520,842 (GRCm39) S655P probably damaging Het
Zmym1 T C 4: 126,948,090 (GRCm39) T94A 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
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
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
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'- CCAGAAAAGCTAGTTGTATGCAG -3'
(R):5'- TTGAAACTTCTGGCCCTTTAGC -3'

Sequencing Primer
(F):5'- GCTAGTTGTATGCAGAACGC -3'
(R):5'- GCCCTTTAGCCCTGATGAAGTAAG -3'
Posted On 2015-12-29