Incidental Mutation 'R7522:Map3k4'
ID 582755
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 045594-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.958) question?
Stock # R7522 (G1)
Quality Score 225.009
Status Validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 12480219 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamine to Arginine at position 661 (Q661R)
Ref Sequence ENSEMBL: ENSMUSP00000086459 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect probably benign
Transcript: ENSMUST00000089058
AA Change: Q661R

PolyPhen 2 Score 0.390 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: Q661R

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 0.1466 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.3%
Validation Efficiency 97% (75/77)
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: 76 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A030014E15Rik G T 1: 82,902,949 (GRCm39) C82F unknown Het
Adam21 G C 12: 81,605,722 (GRCm39) T680R possibly damaging Het
Adgrf4 A C 17: 42,980,675 (GRCm39) Y137D probably benign Het
Ago3 T C 4: 126,257,600 (GRCm39) K477R probably benign Het
Ahnak T A 19: 8,979,686 (GRCm39) D323E probably benign Het
Amph A G 13: 19,270,715 (GRCm39) D108G probably damaging Het
Ankrd10 A T 8: 11,682,910 (GRCm39) C106S probably damaging Het
Bmp5 A T 9: 75,683,384 (GRCm39) T4S probably benign Het
Brix1 G A 15: 10,476,676 (GRCm39) R267C probably damaging Het
Calcrl G A 2: 84,203,708 (GRCm39) S24L probably benign Het
Ccdc40 T G 11: 119,123,047 (GRCm39) I213R possibly damaging Het
Cd300lg A G 11: 101,945,028 (GRCm39) I413V probably benign Het
Cdh3 G A 8: 107,268,005 (GRCm39) D347N probably damaging Het
Clcn3 T C 8: 61,394,446 (GRCm39) T55A probably benign Het
Cnga4 A G 7: 105,055,195 (GRCm39) T260A probably damaging Het
Cpne8 G T 15: 90,486,022 (GRCm39) P147Q probably benign Het
Cpsf6 A G 10: 117,203,734 (GRCm39) Y74H unknown Het
Cryl1 A T 14: 57,513,428 (GRCm39) S264R probably benign Het
Cyp39a1 C T 17: 43,978,370 (GRCm39) probably benign Het
Cyp4f39 T C 17: 32,705,946 (GRCm39) S346P probably damaging Het
Cyria A G 12: 12,408,057 (GRCm39) T28A possibly damaging Het
Ddhd1 G A 14: 45,895,104 (GRCm39) A122V possibly damaging Het
Dnmt1 C A 9: 20,831,498 (GRCm39) C662F probably damaging Het
E2f6 G A 12: 16,872,125 (GRCm39) G190S probably benign Het
Esp34 A T 17: 38,870,432 (GRCm39) I109F possibly damaging Het
Espl1 A T 15: 102,213,486 (GRCm39) D604V probably damaging Het
Exo1 T C 1: 175,728,870 (GRCm39) C645R probably benign Het
Fah A G 7: 84,246,282 (GRCm39) V189A probably benign Het
Fam184b A C 5: 45,688,093 (GRCm39) Y939D probably damaging Het
Fchsd2 T A 7: 100,908,829 (GRCm39) L410* probably null Het
Gak A T 5: 108,739,065 (GRCm39) I665N possibly damaging Het
Galnt9 A G 5: 110,743,705 (GRCm39) probably null Het
Gcg T C 2: 62,306,103 (GRCm39) R165G probably benign Het
Hexd T C 11: 121,108,923 (GRCm39) V214A possibly damaging Het
Hoxb3 A T 11: 96,235,507 (GRCm39) S145C probably damaging Het
Il18 A G 9: 50,486,640 (GRCm39) Y23C probably damaging Het
Itgav A T 2: 83,632,373 (GRCm39) I954F probably benign Het
Kcna4 A G 2: 107,126,600 (GRCm39) R445G probably damaging Het
Kyat3 T A 3: 142,440,305 (GRCm39) L343Q probably damaging Het
Lgals4 A T 7: 28,537,117 (GRCm39) D139V possibly damaging Het
Lrp3 C T 7: 34,903,755 (GRCm39) G197D probably damaging Het
Lyst T A 13: 13,821,668 (GRCm39) C1347* probably null Het
Man2a2 G C 7: 80,018,613 (GRCm39) A82G probably benign Het
Marcks A C 10: 37,012,577 (GRCm39) F153V unknown Het
Mocs1 T C 17: 49,742,292 (GRCm39) probably null Het
Naa60 A G 16: 3,719,768 (GRCm39) T232A probably benign Het
Oosp1 A T 19: 11,666,065 (GRCm39) I75N probably benign Het
Opn3 A G 1: 175,493,189 (GRCm39) V125A probably benign Het
Or2ag18 A G 7: 106,404,994 (GRCm39) V225A probably damaging Het
Or2f1 T A 6: 42,721,568 (GRCm39) I199N probably damaging Het
Or4c102 A G 2: 88,423,005 (GRCm39) T286A possibly damaging Het
Or7g27 T A 9: 19,250,294 (GRCm39) C179* probably null Het
Palb2 T C 7: 121,712,501 (GRCm39) T947A probably damaging Het
Pde5a C T 3: 122,634,648 (GRCm39) R730* probably null Het
Plcl1 T C 1: 55,735,523 (GRCm39) I288T probably benign Het
Plxnb2 A G 15: 89,045,977 (GRCm39) I966T probably benign Het
Prkcz T C 4: 155,355,742 (GRCm39) E400G probably damaging Het
Prpf8 A G 11: 75,400,102 (GRCm39) D2332G possibly damaging Het
Ptgds T G 2: 25,357,920 (GRCm39) T154P probably benign Het
Rel T C 11: 23,720,676 (GRCm39) probably null Het
Rxylt1 A G 10: 121,917,344 (GRCm39) W390R probably damaging Het
Serpinb1c T A 13: 33,066,200 (GRCm39) K248N probably benign Het
Shkbp1 A C 7: 27,046,583 (GRCm39) W394G possibly damaging Het
Slc47a2 A G 11: 61,193,076 (GRCm39) V559A probably benign Het
Sox6 A T 7: 115,400,813 (GRCm39) F10I probably damaging Het
Stkld1 T C 2: 26,837,259 (GRCm39) V303A probably benign Het
Styk1 T A 6: 131,289,803 (GRCm39) probably null Het
Tet1 T C 10: 62,654,762 (GRCm39) T1574A possibly damaging Het
Tkt A T 14: 30,290,180 (GRCm39) I270F possibly damaging Het
Trak1 A G 9: 121,271,777 (GRCm39) E166G probably damaging Het
Tsc2 A T 17: 24,849,939 (GRCm39) I58N probably damaging Het
Uhmk1 T A 1: 170,042,809 (GRCm39) M1L probably benign Het
Usp50 T C 2: 126,625,146 (GRCm39) Y21C probably damaging Het
Vmn1r180 C G 7: 23,652,685 (GRCm39) P283A probably damaging Het
Vmn1r83 A G 7: 12,055,505 (GRCm39) M184T possibly damaging Het
Vmn2r109 A G 17: 20,774,665 (GRCm39) I230T probably benign 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
R4934:Map3k4 UTSW 17 12,490,787 (GRCm39) missense probably damaging 1.00
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
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'- GTATTCCTAAATCCCCACTGTGAC -3'
(R):5'- AAGTTCCTCAGAGGCAGGAC -3'

Sequencing Primer
(F):5'- TGATGGTTAACAGCATATAGACCAAG -3'
(R):5'- GAGGCAGGACCCTCTAGG -3'
Posted On 2019-10-17