Incidental Mutation 'R7120:Map3k4'
ID 551968
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 045209-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.953) question?
Stock # R7120 (G1)
Quality Score 225.009
Status Not validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 12490354 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Alanine to Glutamic Acid at position 359 (A359E)
Ref Sequence ENSEMBL: ENSMUSP00000086459 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect probably damaging
Transcript: ENSMUST00000089058
AA Change: A359E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: A359E

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: 100.0%
  • 10x: 99.8%
  • 20x: 99.4%
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: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1810062G17Rik A T 3: 36,536,016 (GRCm39) Q94L unknown Het
4933411K16Rik C T 19: 42,041,112 (GRCm39) A81V probably benign Het
Actr3 A C 1: 125,331,169 (GRCm39) Y273* probably null Het
Aoc1 T A 6: 48,883,531 (GRCm39) I469N probably damaging Het
Arhgef28 A T 13: 98,081,047 (GRCm39) L1270Q probably damaging Het
Atp2c1 G A 9: 105,297,385 (GRCm39) Q780* probably null Het
Bbs10 T C 10: 111,135,310 (GRCm39) V141A possibly damaging Het
Bivm A T 1: 44,165,606 (GRCm39) T19S probably benign Het
Cacna1h T G 17: 25,610,481 (GRCm39) H675P probably benign Het
Cadps T A 14: 12,439,919 (GRCm38) L1204F probably damaging Het
Cald1 T C 6: 34,663,011 (GRCm39) probably null Het
Calr A G 8: 85,569,457 (GRCm39) M357T probably damaging Het
Ccni A T 5: 93,331,190 (GRCm39) Y260* probably null Het
Csrnp3 C A 2: 65,853,354 (GRCm39) T594K probably damaging Het
Dek A T 13: 47,253,659 (GRCm39) M152K unknown Het
Depdc1b T C 13: 108,498,781 (GRCm39) W155R probably benign Het
Ehd1 A G 19: 6,347,591 (GRCm39) K315R probably benign Het
Epn3 C A 11: 94,383,254 (GRCm39) R323S probably benign Het
Fan1 T A 7: 64,022,234 (GRCm39) N340Y probably damaging Het
Fbxo10 T A 4: 45,040,533 (GRCm39) K891* probably null Het
Fras1 G T 5: 96,900,819 (GRCm39) G3013* probably null Het
Gbp2b A G 3: 142,312,507 (GRCm39) T297A probably benign Het
Gbp7 T C 3: 142,249,734 (GRCm39) S402P probably damaging Het
Gclc T C 9: 77,694,032 (GRCm39) Y329H probably damaging Het
Gfpt1 A G 6: 87,064,375 (GRCm39) H655R probably benign Het
Gm4787 C A 12: 81,425,260 (GRCm39) M299I probably benign Het
Grb7 C A 11: 98,345,817 (GRCm39) R532S probably benign Het
Hmcn1 A T 1: 150,576,292 (GRCm39) I2066N probably damaging Het
Hnrnpll T C 17: 80,341,486 (GRCm39) T518A probably benign Het
Hps3 G A 3: 20,065,705 (GRCm39) R712W probably damaging Het
Hspd1 A G 1: 55,118,388 (GRCm39) V406A probably benign Het
Igkv2-112 T C 6: 68,197,510 (GRCm39) F61L probably benign Het
Iqcf5 G A 9: 106,392,995 (GRCm39) R84H probably damaging Het
Itgad T A 7: 127,773,146 (GRCm39) M1K probably null Het
Kmt2d A G 15: 98,758,946 (GRCm39) S1292P unknown Het
Macc1 C A 12: 119,409,480 (GRCm39) Q83K possibly damaging Het
Mfap3 T A 11: 57,419,043 (GRCm39) C68S probably damaging Het
Mipep C T 14: 61,112,696 (GRCm39) R660C possibly damaging Het
Morc2b A T 17: 33,354,787 (GRCm39) L995Q probably damaging Het
Mrc1 A G 2: 14,313,508 (GRCm39) N913S probably damaging Het
N4bp1 C A 8: 87,587,495 (GRCm39) C481F probably benign Het
Nae1 A G 8: 105,252,910 (GRCm39) probably null Het
Nup214 T A 2: 31,941,054 (GRCm39) V29E probably benign Het
Or1e30 A T 11: 73,677,940 (GRCm39) M59L probably damaging Het
Or8c11 T C 9: 38,289,945 (GRCm39) L250P probably damaging Het
Orai1 A G 5: 123,167,535 (GRCm39) E236G possibly damaging Het
P2rx7 A G 5: 122,819,357 (GRCm39) Y593C probably benign Het
Pcbp2 A G 15: 102,383,113 (GRCm39) D77G possibly damaging Het
Pcdha8 G A 18: 37,126,840 (GRCm39) V441M possibly damaging Het
Peg10 CCACATCAGGATCCACATCAGGATGCACATCAGCATCAGGATCCCCATCAGGATGCACATCAGGATCCACATCAGGATGCACATCAG CCACATCAGGATCCACATCAGGATGCACATCAG 6: 4,756,398 (GRCm39) probably benign Het
Plaa A G 4: 94,470,919 (GRCm39) S406P possibly damaging Het
Plekhh1 C A 12: 79,117,713 (GRCm39) P903Q probably benign Het
Plekhh3 T C 11: 101,059,064 (GRCm39) E92G probably damaging Het
Ptpn9 T C 9: 56,967,166 (GRCm39) F463S probably damaging Het
Ptprn2 A C 12: 116,835,676 (GRCm39) E337A probably benign Het
Rubcn C T 16: 32,656,839 (GRCm39) R527Q probably damaging Het
Samd3 C T 10: 26,106,864 (GRCm39) T73M possibly damaging Het
Sfxn4 T A 19: 60,840,477 (GRCm39) K173* probably null Het
Son CATGGACTCCCAGATGTTAGCAACTAGCTCTATGGACTCCCAGATGTTAGCAACTAGCTCTATGGACTCCCAGATGTTAGCAACCAGCAGTATGGACTCCCAGATGTTAGCAACCAGCAGTATGGACTCCCAGATGTTAGCAACCAGCTCCATGGACTCCCAGATGTTAGCAAC CATGGACTCCCAGATGTTAGCAACTAGCTCTATGGACTCCCAGATGTTAGCAACCAGCAGTATGGACTCCCAGATGTTAGCAACCAGCAGTATGGACTCCCAGATGTTAGCAACCAGCTCCATGGACTCCCAGATGTTAGCAAC 16: 91,453,579 (GRCm39) probably benign Het
Son T G 16: 91,467,414 (GRCm39) N2258K unknown Het
Sspo A T 6: 48,442,505 (GRCm39) H2000L probably benign Het
Syne1 C T 10: 5,243,971 (GRCm39) S2731N probably benign Het
Syt6 T C 3: 103,494,673 (GRCm39) Y213H probably damaging Het
Tkt A G 14: 30,281,779 (GRCm39) N99S probably benign Het
Tlcd3b T C 7: 126,428,505 (GRCm39) L221P probably damaging Het
Tmem258 G A 19: 10,181,602 (GRCm39) probably benign Het
Tnks1bp1 T C 2: 84,902,441 (GRCm39) S1702P probably damaging Het
Tpte A G 8: 22,817,689 (GRCm39) D225G probably damaging Het
Trak1 T A 9: 121,289,564 (GRCm39) F625L probably benign Het
Ttc33 G T 15: 5,241,488 (GRCm39) C77F probably benign Het
Ugt1a2 A G 1: 88,128,522 (GRCm39) H55R probably damaging Het
Vmn1r169 G T 7: 23,277,444 (GRCm39) V279L probably benign Het
Vmn2r25 T C 6: 123,805,394 (GRCm39) K488E possibly damaging Het
Vmn2r8 A T 5: 108,956,504 (GRCm39) D39E 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
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
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'- GGGGATTTCAAACACTGGCC -3'
(R):5'- GATCCTCACCTTCAAAGTTAACTACG -3'

Sequencing Primer
(F):5'- GCCAGCCAATGTCTGATAGGTTC -3'
(R):5'- TTAACTACGGGAGCATTGCC -3'
Posted On 2019-05-15