Incidental Mutation 'R4934:Map3k4'
ID 380867
Institutional Source Beutler Lab
Gene Symbol Map3k4
Ensembl Gene ENSMUSG00000014426
Gene Name mitogen-activated protein kinase kinase kinase 4
Synonyms T-associated sex reversal, D17Rp17, D17Rp17e, Mekk4, Tas, RP17, MAPKKK4, MTK1
MMRRC Submission 042534-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.953) question?
Stock # R4934 (G1)
Quality Score 225
Status Validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 12490787 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Cysteine at position 215 (R215C)
Ref Sequence ENSEMBL: ENSMUSP00000086459 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect probably damaging
Transcript: ENSMUST00000089058
AA Change: R215C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: R215C

DomainStartEndE-ValueType
low complexity region 8 21 N/A INTRINSIC
low complexity region 27 43 N/A INTRINSIC
low complexity region 215 235 N/A INTRINSIC
low complexity region 432 462 N/A INTRINSIC
low complexity region 1177 1191 N/A INTRINSIC
S_TKc 1332 1590 1.41e-91 SMART
Meta Mutation Damage Score 0.8802 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.3%
  • 10x: 96.0%
  • 20x: 91.4%
Validation Efficiency 99% (134/135)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]
PHENOTYPE: Homozygous null mice exhibit some perinatal lethality and survivors appear smaller. On certain genetic backgrounds, heterozygous X/Y mice may develop as phenotypic females or hermaphrodites. The sex-reversal phenotype is dependent on a combination of strain-specific autosomal and Y-linked alleles. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 125 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4931428L18Rik A T 1: 31,261,580 (GRCm39) probably benign Het
Acy1 T A 9: 106,312,321 (GRCm39) I14F probably null Het
Ago1 T C 4: 126,342,652 (GRCm39) D193G possibly damaging Het
Arhgap45 A T 10: 79,856,791 (GRCm39) H201L probably damaging Het
Armc9 G A 1: 86,140,801 (GRCm39) D63N probably damaging Het
Asb17 A T 3: 153,556,336 (GRCm39) I148F possibly damaging Het
Atf7ip2 A G 16: 10,059,447 (GRCm39) E329G possibly damaging Het
Atp2a1 T A 7: 126,052,600 (GRCm39) D373V probably benign Het
Cacna1e G T 1: 154,357,380 (GRCm39) Y603* probably null Het
Cbln4 G A 2: 171,880,901 (GRCm39) T131I probably damaging Het
Ccdc126 A G 6: 49,311,181 (GRCm39) E63G probably damaging Het
Ccl4 T A 11: 83,553,504 (GRCm39) S6T unknown Het
Ccnb1 A T 13: 100,918,209 (GRCm39) I146K possibly damaging Het
Ccr8 T A 9: 119,923,815 (GRCm39) M310K probably benign Het
Cd180 A T 13: 102,875,672 (GRCm39) probably null Het
Cd46 G C 1: 194,765,107 (GRCm39) probably benign Het
Cebpb A G 2: 167,531,005 (GRCm39) M22V probably benign Het
Cep152 A G 2: 125,453,016 (GRCm39) I352T possibly damaging Het
Cep295 T G 9: 15,244,456 (GRCm39) E1333D probably damaging Het
Ces4a A G 8: 105,864,613 (GRCm39) H30R probably benign Het
Chrm3 A G 13: 9,927,450 (GRCm39) Y529H probably damaging Het
Chrnb4 T C 9: 54,942,101 (GRCm39) Y391C probably benign Het
Clca3a2 A G 3: 144,523,692 (GRCm39) Y98H probably damaging Het
Clvs1 C T 4: 9,424,216 (GRCm39) H221Y possibly damaging Het
Col3a1 G A 1: 45,379,112 (GRCm39) probably benign Het
Cpn2 T G 16: 30,079,344 (GRCm39) N119T probably damaging Het
Cspg4b C A 13: 113,504,882 (GRCm39) Q2004K probably damaging Het
Cubn T A 2: 13,494,721 (GRCm39) Q109H probably benign Het
Cyp26b1 A G 6: 84,553,954 (GRCm39) V221A possibly damaging Het
Cyp2e1 T G 7: 140,350,030 (GRCm39) N238K probably damaging Het
Dst C T 1: 34,247,669 (GRCm39) A1693V probably damaging Het
Dync2li1 A G 17: 84,956,683 (GRCm39) Q281R probably benign Het
Enpp2 C T 15: 54,745,543 (GRCm39) G318S probably damaging Het
Entrep1 T C 19: 23,950,789 (GRCm39) *597W probably null Het
F13a1 G T 13: 37,061,736 (GRCm39) P676T probably benign Het
Fam227a T C 15: 79,521,262 (GRCm39) H267R possibly damaging Het
Fam78a G A 2: 31,959,427 (GRCm39) R228C probably damaging Het
Fbxw25 T C 9: 109,480,705 (GRCm39) N325S possibly damaging Het
Foxred1 T C 9: 35,121,210 (GRCm39) probably benign Het
Fstl5 T A 3: 76,496,272 (GRCm39) V345E probably damaging Het
Fzd8 GAAAAACTCA GA 18: 9,214,492 (GRCm39) probably null Het
Hand1 T C 11: 57,722,078 (GRCm39) R179G possibly damaging Het
Hk1 G T 10: 62,194,165 (GRCm39) probably benign Het
Hmcn1 A C 1: 150,598,286 (GRCm39) L1672R probably damaging Het
Hps5 G A 7: 46,418,775 (GRCm39) Q297* probably null Het
Iars1 T A 13: 49,871,460 (GRCm39) F699I probably benign Het
Ift140 G A 17: 25,267,462 (GRCm39) G620E probably benign Het
Igkv4-80 A C 6: 68,993,649 (GRCm39) S81A probably benign Het
Inpp4a T G 1: 37,426,922 (GRCm39) Y628D possibly damaging Het
Itk C T 11: 46,280,152 (GRCm39) R29H probably damaging Het
Kcnv1 A G 15: 44,972,644 (GRCm39) F413S probably damaging Het
Klhl3 A T 13: 58,250,231 (GRCm39) Y4* probably null Het
Lonrf1 C A 8: 36,701,103 (GRCm39) C369F probably damaging Het
Magohb A T 6: 131,261,558 (GRCm39) probably benign Het
Map3k8 A T 18: 4,339,548 (GRCm39) S274R possibly damaging Het
Masp1 T G 16: 23,283,826 (GRCm39) M470L probably damaging Het
Mfng C T 15: 78,648,588 (GRCm39) R163H probably benign Het
Muc4 A T 16: 32,576,472 (GRCm39) probably benign Het
Myo1c T A 11: 75,562,676 (GRCm39) V981E probably damaging Het
Nedd9 A T 13: 41,492,411 (GRCm39) I27K probably damaging Het
Nkd2 C A 13: 73,970,841 (GRCm39) G247V probably damaging Het
Nucb2 A C 7: 116,139,199 (GRCm39) Q398P possibly damaging Het
Numa1 T A 7: 101,660,064 (GRCm39) D376E probably benign Het
Or2w1 G A 13: 21,317,241 (GRCm39) V99I probably benign Het
Or4c101 C T 2: 88,389,930 (GRCm39) T39I probably benign Het
Or4n5 T C 14: 50,133,206 (GRCm39) T18A probably benign Het
Or4p23 A T 2: 88,576,398 (GRCm39) L278* probably null Het
Or4q3 C T 14: 50,583,345 (GRCm39) V185M probably damaging Het
Or5b119 G A 19: 13,456,956 (GRCm39) T202I possibly damaging Het
Or6c76b A T 10: 129,692,896 (GRCm39) N170Y possibly damaging Het
Or8d23 A T 9: 38,842,129 (GRCm39) I221F probably damaging Het
Otx1 C A 11: 21,947,037 (GRCm39) A91S probably damaging Het
Pamr1 C T 2: 102,472,549 (GRCm39) T616I probably benign Het
Pcnx1 G A 12: 82,038,599 (GRCm39) V1955I possibly damaging Het
Pira13 A G 7: 3,825,676 (GRCm39) Y398H probably damaging Het
Plekha3 T A 2: 76,510,571 (GRCm39) D35E possibly damaging Het
Pnpla2 T G 7: 141,038,085 (GRCm39) N184K probably damaging Het
Polr3a C T 14: 24,502,692 (GRCm39) E1216K probably benign Het
Ppp1r21 A T 17: 88,852,803 (GRCm39) S61C probably damaging Het
Ppp1r21 G C 17: 88,852,804 (GRCm39) S61T probably damaging Het
Prdm13 G T 4: 21,678,223 (GRCm39) probably benign Het
Prss53 T C 7: 127,487,879 (GRCm39) N201S probably benign Het
Rab11fip2 A G 19: 59,924,290 (GRCm39) L338S probably damaging Het
Rad50 T C 11: 53,575,102 (GRCm39) N546S probably benign Het
Ralgapa1 T C 12: 55,809,359 (GRCm39) D472G possibly damaging Het
Rexo4 A G 2: 26,850,346 (GRCm39) I277T probably damaging Het
Rimbp2 C T 5: 128,865,579 (GRCm39) V590I probably benign Het
Ripor3 A G 2: 167,824,736 (GRCm39) V864A probably benign Het
Rnpc3 G A 3: 113,418,628 (GRCm39) H107Y possibly damaging Het
Ryr1 A T 7: 28,767,520 (GRCm39) D2927E probably damaging Het
Samd9l G A 6: 3,375,621 (GRCm39) Q547* probably null Het
Scaper T C 9: 55,716,459 (GRCm39) E724G probably damaging Het
Secisbp2l C T 2: 125,582,409 (GRCm39) V1016I probably damaging Het
Selenoo T A 15: 88,982,970 (GRCm39) M499K probably damaging Het
Sema4a T A 3: 88,345,568 (GRCm39) D505V probably damaging Het
Sema5a T C 15: 32,679,310 (GRCm39) M863T probably damaging Het
Slc24a5 T C 2: 124,929,940 (GRCm39) C414R probably damaging Het
Slc34a2 A G 5: 53,224,942 (GRCm39) D361G probably damaging Het
Slc5a1 T C 5: 33,261,858 (GRCm39) Y20H probably benign Het
Slx4ip A T 2: 136,910,267 (GRCm39) probably benign Het
Snx14 T A 9: 88,280,341 (GRCm39) E538V probably damaging Het
Sspo C A 6: 48,442,486 (GRCm39) L1994I probably damaging Het
St13 G C 15: 81,283,786 (GRCm39) R4G probably benign Het
Stap2 A G 17: 56,304,901 (GRCm39) S294P possibly damaging Het
Stat1 C A 1: 52,193,082 (GRCm39) Y651* probably null Het
Syne2 A G 12: 75,946,046 (GRCm39) T373A probably benign Het
Tacc2 A G 7: 130,330,318 (GRCm39) S201G probably damaging Het
Tdpoz3 G A 3: 93,734,287 (GRCm39) E321K probably benign Het
Thumpd1 T C 7: 119,316,002 (GRCm39) T316A probably benign Het
Tlr3 A T 8: 45,850,072 (GRCm39) C866S probably benign Het
Tmprss11g T A 5: 86,644,401 (GRCm39) I148F probably benign Het
Topbp1 T A 9: 103,205,568 (GRCm39) probably benign Het
Tpm1 T C 9: 66,935,331 (GRCm39) probably null Het
Traf3ip2 T A 10: 39,502,096 (GRCm39) S81R probably damaging Het
Trim29 T A 9: 43,222,265 (GRCm39) N31K probably benign Het
Ubn2 C T 6: 38,467,433 (GRCm39) P563S probably benign Het
Usp24 T C 4: 106,283,743 (GRCm39) Y2418H probably benign Het
Vmn2r6 T A 3: 64,463,766 (GRCm39) D267V probably damaging Het
Wapl T A 14: 34,414,052 (GRCm39) C305S probably benign Het
Yme1l1 C A 2: 23,058,333 (GRCm39) S155* probably null Het
Ythdf3 T A 3: 16,258,220 (GRCm39) H126Q probably damaging Het
Zbtb32 A T 7: 30,290,678 (GRCm39) C206S possibly damaging Het
Zbtb47 T C 9: 121,593,045 (GRCm39) V455A probably damaging Het
Zfp518a A T 19: 40,902,707 (GRCm39) I879F probably benign Het
Zfp938 A T 10: 82,062,012 (GRCm39) Y203N possibly damaging Het
Other mutations in Map3k4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01065:Map3k4 APN 17 12,451,877 (GRCm39) missense probably damaging 1.00
IGL01124:Map3k4 APN 17 12,474,087 (GRCm39) missense probably benign 0.01
IGL01125:Map3k4 APN 17 12,490,849 (GRCm39) missense probably damaging 0.96
IGL01585:Map3k4 APN 17 12,467,846 (GRCm39) missense probably damaging 1.00
IGL02194:Map3k4 APN 17 12,482,815 (GRCm39) missense probably damaging 1.00
IGL02194:Map3k4 APN 17 12,467,882 (GRCm39) missense probably benign 0.30
IGL02292:Map3k4 APN 17 12,454,045 (GRCm39) missense possibly damaging 0.77
IGL02326:Map3k4 APN 17 12,467,897 (GRCm39) missense probably damaging 1.00
IGL02388:Map3k4 APN 17 12,490,497 (GRCm39) missense probably damaging 0.99
IGL02621:Map3k4 APN 17 12,482,900 (GRCm39) missense probably damaging 1.00
IGL02668:Map3k4 APN 17 12,454,840 (GRCm39) missense possibly damaging 0.85
IGL02850:Map3k4 APN 17 12,490,801 (GRCm39) missense probably damaging 1.00
IGL02939:Map3k4 APN 17 12,491,036 (GRCm39) missense probably damaging 1.00
IGL03148:Map3k4 APN 17 12,457,045 (GRCm39) missense probably benign 0.01
IGL03238:Map3k4 APN 17 12,490,045 (GRCm39) missense probably benign 0.10
ANU74:Map3k4 UTSW 17 12,451,863 (GRCm39) missense probably damaging 1.00
R0012:Map3k4 UTSW 17 12,457,076 (GRCm39) missense probably damaging 1.00
R0012:Map3k4 UTSW 17 12,457,076 (GRCm39) missense probably damaging 1.00
R0128:Map3k4 UTSW 17 12,466,950 (GRCm39) missense probably damaging 0.99
R0183:Map3k4 UTSW 17 12,454,015 (GRCm39) missense probably damaging 1.00
R0309:Map3k4 UTSW 17 12,489,902 (GRCm39) frame shift probably null
R0355:Map3k4 UTSW 17 12,473,058 (GRCm39) missense probably damaging 1.00
R0367:Map3k4 UTSW 17 12,476,928 (GRCm39) splice site probably benign
R1103:Map3k4 UTSW 17 12,455,950 (GRCm39) splice site probably null
R1446:Map3k4 UTSW 17 12,475,681 (GRCm39) nonsense probably null
R1542:Map3k4 UTSW 17 12,454,793 (GRCm39) missense probably damaging 0.97
R1713:Map3k4 UTSW 17 12,468,458 (GRCm39) missense probably benign 0.39
R1777:Map3k4 UTSW 17 12,490,617 (GRCm39) missense possibly damaging 0.82
R1797:Map3k4 UTSW 17 12,482,906 (GRCm39) missense probably benign 0.30
R1997:Map3k4 UTSW 17 12,473,882 (GRCm39) critical splice donor site probably null
R2042:Map3k4 UTSW 17 12,496,870 (GRCm39) missense probably damaging 0.99
R2878:Map3k4 UTSW 17 12,482,954 (GRCm39) missense probably benign 0.00
R2939:Map3k4 UTSW 17 12,480,157 (GRCm39) missense probably damaging 0.98
R2940:Map3k4 UTSW 17 12,480,157 (GRCm39) missense probably damaging 0.98
R3405:Map3k4 UTSW 17 12,475,668 (GRCm39) missense probably damaging 1.00
R3930:Map3k4 UTSW 17 12,454,880 (GRCm39) missense possibly damaging 0.83
R4291:Map3k4 UTSW 17 12,474,147 (GRCm39) missense probably benign 0.08
R4410:Map3k4 UTSW 17 12,467,885 (GRCm39) missense probably damaging 1.00
R4632:Map3k4 UTSW 17 12,451,391 (GRCm39) missense probably damaging 1.00
R4641:Map3k4 UTSW 17 12,482,932 (GRCm39) missense probably damaging 1.00
R4726:Map3k4 UTSW 17 12,451,851 (GRCm39) missense possibly damaging 0.89
R4730:Map3k4 UTSW 17 12,467,861 (GRCm39) missense probably damaging 0.99
R4832:Map3k4 UTSW 17 12,490,667 (GRCm39) missense probably damaging 1.00
R4896:Map3k4 UTSW 17 12,490,906 (GRCm39) missense possibly damaging 0.65
R4971:Map3k4 UTSW 17 12,468,382 (GRCm39) critical splice donor site probably null
R4980:Map3k4 UTSW 17 12,490,958 (GRCm39) missense probably damaging 1.00
R5211:Map3k4 UTSW 17 12,451,321 (GRCm39) missense possibly damaging 0.88
R5337:Map3k4 UTSW 17 12,490,497 (GRCm39) missense probably damaging 0.99
R5356:Map3k4 UTSW 17 12,466,195 (GRCm39) missense possibly damaging 0.87
R5550:Map3k4 UTSW 17 12,462,445 (GRCm39) nonsense probably null
R5824:Map3k4 UTSW 17 12,448,526 (GRCm39) missense probably damaging 1.00
R5890:Map3k4 UTSW 17 12,490,303 (GRCm39) missense probably damaging 1.00
R6285:Map3k4 UTSW 17 12,482,945 (GRCm39) missense probably damaging 1.00
R6380:Map3k4 UTSW 17 12,490,954 (GRCm39) missense possibly damaging 0.56
R6383:Map3k4 UTSW 17 12,468,470 (GRCm39) missense possibly damaging 0.82
R6571:Map3k4 UTSW 17 12,461,579 (GRCm39) missense possibly damaging 0.80
R6584:Map3k4 UTSW 17 12,479,378 (GRCm39) missense probably damaging 1.00
R6616:Map3k4 UTSW 17 12,490,231 (GRCm39) missense probably damaging 1.00
R6644:Map3k4 UTSW 17 12,451,297 (GRCm39) critical splice donor site probably null
R6909:Map3k4 UTSW 17 12,489,872 (GRCm39) missense probably damaging 1.00
R6947:Map3k4 UTSW 17 12,479,456 (GRCm39) nonsense probably null
R6970:Map3k4 UTSW 17 12,467,803 (GRCm39) missense probably damaging 1.00
R7120:Map3k4 UTSW 17 12,490,354 (GRCm39) missense probably damaging 1.00
R7253:Map3k4 UTSW 17 12,490,955 (GRCm39) missense probably benign 0.00
R7267:Map3k4 UTSW 17 12,490,536 (GRCm39) nonsense probably null
R7322:Map3k4 UTSW 17 12,489,833 (GRCm39) missense probably damaging 1.00
R7522:Map3k4 UTSW 17 12,480,219 (GRCm39) missense probably benign 0.39
R7554:Map3k4 UTSW 17 12,451,301 (GRCm39) nonsense probably null
R7554:Map3k4 UTSW 17 12,451,300 (GRCm39) missense probably damaging 1.00
R7681:Map3k4 UTSW 17 12,537,430 (GRCm39) missense unknown
R7734:Map3k4 UTSW 17 12,482,998 (GRCm39) missense probably damaging 1.00
R7842:Map3k4 UTSW 17 12,490,030 (GRCm39) missense possibly damaging 0.54
R8013:Map3k4 UTSW 17 12,489,918 (GRCm39) nonsense probably null
R8014:Map3k4 UTSW 17 12,489,918 (GRCm39) nonsense probably null
R8235:Map3k4 UTSW 17 12,458,968 (GRCm39) splice site probably null
R8294:Map3k4 UTSW 17 12,537,500 (GRCm39) missense unknown
R8528:Map3k4 UTSW 17 12,451,821 (GRCm39) missense probably damaging 1.00
R8858:Map3k4 UTSW 17 12,490,759 (GRCm39) missense probably damaging 1.00
R8924:Map3k4 UTSW 17 12,490,433 (GRCm39) missense probably benign 0.00
R9063:Map3k4 UTSW 17 12,482,878 (GRCm39) missense probably damaging 1.00
R9224:Map3k4 UTSW 17 12,456,973 (GRCm39) missense probably damaging 0.99
R9446:Map3k4 UTSW 17 12,451,375 (GRCm39) missense probably damaging 1.00
R9486:Map3k4 UTSW 17 12,489,860 (GRCm39) missense probably damaging 1.00
R9488:Map3k4 UTSW 17 12,489,860 (GRCm39) missense probably damaging 1.00
R9591:Map3k4 UTSW 17 12,454,795 (GRCm39) missense possibly damaging 0.91
R9617:Map3k4 UTSW 17 12,476,871 (GRCm39) missense possibly damaging 0.67
R9722:Map3k4 UTSW 17 12,490,523 (GRCm39) missense probably benign 0.01
X0067:Map3k4 UTSW 17 12,482,981 (GRCm39) missense probably benign 0.03
Z1177:Map3k4 UTSW 17 12,490,584 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- AAGAGGTCCTGGTCATTGATGG -3'
(R):5'- AACTCTGAGAACAACGGAGC -3'

Sequencing Primer
(F):5'- TCATTGATGGTGCGGCCC -3'
(R):5'- AATGCACAGTGCTCGTTCATG -3'
Posted On 2016-04-15