Incidental Mutation 'R9486:Map3k4'
ID 716621
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
Accession Numbers
Essential gene? Probably essential (E-score: 0.953) question?
Stock # R9486 (G1)
Quality Score 225.009
Status Not validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 12489860 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Alanine to Threonine at position 524 (A524T)
Ref Sequence ENSEMBL: ENSMUSP00000086459 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect probably damaging
Transcript: ENSMUST00000089058
AA Change: A524T

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: A524T

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.8%
Validation Efficiency
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: 70 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2ml1 A G 6: 128,546,942 (GRCm39) F396L probably damaging Het
Abca13 T C 11: 9,240,621 (GRCm39) I828T possibly damaging Het
Ace3 A T 11: 105,896,219 (GRCm39) T722S probably benign Het
Acot2 A G 12: 84,039,426 (GRCm39) T312A probably benign Het
Adra2a A G 19: 54,035,963 (GRCm39) I440V probably damaging Het
Arhgap22 T A 14: 33,073,303 (GRCm39) M4K probably benign Het
Atp8b3 C T 10: 80,366,821 (GRCm39) C259Y probably damaging Het
Bcl2 T A 1: 106,471,109 (GRCm39) Y199F probably benign Het
Brca1 A T 11: 101,414,520 (GRCm39) C1205S probably benign Het
Col7a1 T C 9: 108,811,396 (GRCm39) V2743A unknown Het
Crybg1 A G 10: 43,880,145 (GRCm39) probably benign Het
Cyp2c40 T A 19: 39,755,808 (GRCm39) H502L probably benign Het
Cyp2c40 A T 19: 39,796,050 (GRCm39) Y109* probably null Het
Cyp4a29 T C 4: 115,106,916 (GRCm39) M191T probably damaging Het
Dcaf1 A G 9: 106,735,916 (GRCm39) R955G possibly damaging Het
Dcaf4 G T 12: 83,582,726 (GRCm39) A274S probably damaging Het
Dlx1 A G 2: 71,362,828 (GRCm39) H245R probably damaging Het
Dnah14 A G 1: 181,508,494 (GRCm39) N1891D possibly damaging Het
Dock10 A T 1: 80,479,452 (GRCm39) V2167D unknown Het
Epyc A G 10: 97,511,697 (GRCm39) Q230R probably benign Het
Etnk1 G A 6: 143,130,310 (GRCm39) R143H probably damaging Het
Fhip2b T C 14: 70,826,479 (GRCm39) D203G probably benign Het
Fmo2 T C 1: 162,708,292 (GRCm39) E281G probably damaging Het
Gm2042 T A 12: 87,925,963 (GRCm39) Y304N possibly damaging Het
Hecw2 T C 1: 53,852,466 (GRCm39) D1551G probably damaging Het
Hgd A T 16: 37,413,811 (GRCm39) D91V probably benign Het
Hspa12a A G 19: 58,797,891 (GRCm39) F276L probably benign Het
Ifitm10 C T 7: 141,909,812 (GRCm39) V95M probably damaging Het
Ints3 G A 3: 90,313,579 (GRCm39) R350* probably null Het
Kdm4c T A 4: 74,252,966 (GRCm39) I511K probably benign Het
Kif27 A G 13: 58,492,348 (GRCm39) S264P probably damaging Het
L1td1 A G 4: 98,624,899 (GRCm39) T365A probably benign Het
Ltbp2 T A 12: 84,878,648 (GRCm39) T304S possibly damaging Het
Mamdc4 T A 2: 25,455,164 (GRCm39) Y962F probably benign Het
Mfsd8 C T 3: 40,789,627 (GRCm39) R140H probably damaging Het
Mmp3 A G 9: 7,451,256 (GRCm39) I331V possibly damaging Het
Mpdz T A 4: 81,254,043 (GRCm39) I1030F probably damaging Het
Mtx1 A T 3: 89,120,163 (GRCm39) C62S Het
Muc20 A T 16: 32,615,248 (GRCm39) V43E possibly damaging Het
Naa25 A G 5: 121,577,958 (GRCm39) E955G probably damaging Het
Nelfcd A G 2: 174,268,635 (GRCm39) Y562C probably damaging Het
Nsd2 T A 5: 34,018,493 (GRCm39) M509K probably benign Het
Obscn T C 11: 58,918,272 (GRCm39) T207A Het
Or1ad1 T A 11: 50,875,691 (GRCm39) H54Q possibly damaging Het
Or4a39 C T 2: 89,236,959 (GRCm39) V155M possibly damaging Het
Or4k5 T A 14: 50,385,672 (GRCm39) I220L probably benign Het
Osbpl11 A T 16: 33,006,283 (GRCm39) N37I possibly damaging Het
Pcdh9 A G 14: 93,797,956 (GRCm39) S1032P possibly damaging Het
Pde6b T A 5: 108,551,241 (GRCm39) I175N probably damaging Het
Pfkl T A 10: 77,824,184 (GRCm39) M735L probably benign Het
Pkp4 T C 2: 59,138,722 (GRCm39) V324A probably benign Het
Ptprb T A 10: 116,155,494 (GRCm39) C462* probably null Het
Rasal3 T C 17: 32,617,910 (GRCm39) N221S probably benign Het
Reep1 A T 6: 71,684,969 (GRCm39) I6F probably benign Het
Rhobtb1 T A 10: 69,106,621 (GRCm39) F457L probably damaging Het
Ryr1 T C 7: 28,777,965 (GRCm39) N2184S probably benign Het
Scn11a T G 9: 119,624,774 (GRCm39) H516P possibly damaging Het
Sipa1l1 T C 12: 82,404,139 (GRCm39) probably null Het
Slc17a7 A G 7: 44,821,606 (GRCm39) N381S possibly damaging Het
Slc38a3 C T 9: 107,536,322 (GRCm39) V25M probably benign Het
Spag1 T G 15: 36,181,954 (GRCm39) D37E probably damaging Het
Spib G T 7: 44,178,815 (GRCm39) D114E possibly damaging Het
Tpx2 A T 2: 152,726,933 (GRCm39) Y400F probably damaging Het
Trhde A G 10: 114,532,014 (GRCm39) I362T possibly damaging Het
Usp17ld C T 7: 102,899,381 (GRCm39) G517E probably benign Het
Vmn1r22 A T 6: 57,877,404 (GRCm39) M191K probably damaging Het
Wdr6 G A 9: 108,453,182 (GRCm39) R234C probably damaging Het
Zdhhc22 C T 12: 87,030,398 (GRCm39) M183I probably benign Het
Zfp1007 C A 5: 109,824,062 (GRCm39) G463* probably null Het
Zfp949 C A 9: 88,452,182 (GRCm39) T584N 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
R7522:Map3k4 UTSW 17 12,480,219 (GRCm39) missense probably benign 0.39
R7554:Map3k4 UTSW 17 12,451,300 (GRCm39) missense probably damaging 1.00
R7554:Map3k4 UTSW 17 12,451,301 (GRCm39) nonsense probably null
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
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'- TACACGGCAAGAGGGATTTG -3'
(R):5'- AGTGTTTGAAATCCCCTCCC -3'

Sequencing Primer
(F):5'- TTTGAGACGTGACACTACGG -3'
(R):5'- AGTGACGAGGAGCCAACCC -3'
Posted On 2022-07-18