Incidental Mutation 'R8924:Map3k4'
ID 679507
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 068769-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.953) question?
Stock # R8924 (G1)
Quality Score 225.009
Status Validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 12490433 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Histidine at position 333 (Y333H)
Ref Sequence ENSEMBL: ENSMUSP00000086459 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect probably benign
Transcript: ENSMUST00000089058
AA Change: Y333H

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: Y333H

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 0.0846 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.0%
Validation Efficiency 98% (88/90)
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: 90 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca8b A G 11: 109,838,003 (GRCm39) V1145A probably benign Het
Ank1 T C 8: 23,589,011 (GRCm39) M562T probably benign Het
Atn1 A T 6: 124,722,211 (GRCm39) S881T probably benign Het
B3galt1 C T 2: 67,949,059 (GRCm39) T258I probably benign Het
Bahcc1 C T 11: 120,167,591 (GRCm39) L1331F probably benign Het
Capn12 G A 7: 28,582,628 (GRCm39) V168M probably damaging Het
Card14 T C 11: 119,216,930 (GRCm39) V338A possibly damaging Het
Cd27 T C 6: 125,213,432 (GRCm39) probably benign Het
Cd37 A G 7: 44,888,109 (GRCm39) L37P probably damaging Het
Cd96 A G 16: 45,919,385 (GRCm39) L212P probably damaging Het
Celsr1 T C 15: 85,916,671 (GRCm39) E434G possibly damaging Het
Cep152 A G 2: 125,444,778 (GRCm39) M456T possibly damaging Het
Ces3b G A 8: 105,811,619 (GRCm39) R45H probably benign Het
Cfap54 T G 10: 92,837,685 (GRCm39) T1072P probably damaging Het
Chodl A T 16: 78,738,659 (GRCm39) M172L possibly damaging Het
Cilp2 A G 8: 70,339,108 (GRCm39) S47P probably damaging Het
Clasrp T C 7: 19,318,232 (GRCm39) I596V unknown Het
Clcn2 C T 16: 20,530,930 (GRCm39) V267I probably damaging Het
Cntln T A 4: 84,806,936 (GRCm39) D139E probably damaging Het
Cyp2j12 A C 4: 95,994,685 (GRCm39) N379K probably damaging Het
Defb21 T C 2: 152,416,704 (GRCm39) V60A possibly damaging Het
Dnajc16 G T 4: 141,494,018 (GRCm39) S543* probably null Het
Efcab12 G T 6: 115,800,664 (GRCm39) H120N probably benign Het
Efcab3 AACTCTA AA 11: 104,806,253 (GRCm39) probably null Het
Efl1 G A 7: 82,412,161 (GRCm39) G850D probably benign Het
Efna1 T C 3: 89,183,635 (GRCm39) M64V probably benign Het
Eif2ak3 T C 6: 70,870,003 (GRCm39) W897R probably damaging Het
Eif2ak4 T A 2: 118,258,513 (GRCm39) F621Y probably damaging Het
Erbin C A 13: 103,975,966 (GRCm39) E643* probably null Het
Esr1 G A 10: 4,807,176 (GRCm39) W364* probably null Het
Fam171a2 T C 11: 102,330,861 (GRCm39) E206G possibly damaging Het
Fam90a1a T C 8: 22,451,429 (GRCm39) F97L probably benign Het
Fap A T 2: 62,378,165 (GRCm39) F181I probably benign Het
Fem1b T C 9: 62,704,916 (GRCm39) N115D probably damaging Het
Gal3st2b G T 1: 93,868,653 (GRCm39) A295S probably benign Het
Galnt10 G A 11: 57,674,681 (GRCm39) probably benign Het
Gcfc2 T C 6: 81,909,879 (GRCm39) V224A probably damaging Het
Gh T C 11: 106,191,634 (GRCm39) E136G probably damaging Het
Gjd3 C T 11: 98,873,325 (GRCm39) C173Y probably damaging Het
Gm12695 T A 4: 96,651,046 (GRCm39) M136L probably benign Het
Gnas A G 2: 174,141,277 (GRCm39) E482G unknown Het
Gpa33 T C 1: 165,980,351 (GRCm39) L138P probably damaging Het
Hlf T C 11: 90,236,714 (GRCm39) D181G probably damaging Het
Irgm1 A G 11: 48,756,698 (GRCm39) L387S probably benign Het
Kctd1 T C 18: 15,102,745 (GRCm39) E812G possibly damaging Het
Klra2 T C 6: 131,205,214 (GRCm39) E209G probably benign Het
Klra3 C T 6: 130,312,732 (GRCm39) V11M probably benign Het
Klrh1 G T 6: 129,745,084 (GRCm39) H171N probably benign Het
Kmt2c T C 5: 25,503,885 (GRCm39) S3808G probably benign Het
Krtap24-1 A C 16: 88,408,888 (GRCm39) S79R probably benign Het
Limch1 T A 5: 67,190,475 (GRCm39) H759Q probably benign Het
Mmel1 A G 4: 154,974,091 (GRCm39) Y377C probably damaging Het
Ms4a14 A T 19: 11,281,113 (GRCm39) Y482N possibly damaging Het
Myo9b A G 8: 71,801,675 (GRCm39) S1277G probably benign Het
Nab1 T C 1: 52,529,667 (GRCm39) T77A possibly damaging Het
Obsl1 T C 1: 75,482,841 (GRCm39) S10G probably benign Het
Odc1 A G 12: 17,598,329 (GRCm39) T157A possibly damaging Het
Or2a5 T G 6: 42,873,964 (GRCm39) L193R probably damaging Het
Or8b52 T C 9: 38,576,780 (GRCm39) D120G probably damaging Het
Peg10 CCACATCAGGATCCACATCAGGATGCACATCAGCATCAGGATCCCCATCAGGATGCACATCAGGATCCACATCAGGATGCACATCAG CCACATCAGGATCCACATCAGGATGCACATCAG 6: 4,756,398 (GRCm39) probably benign Het
Plpp1 T A 13: 112,943,057 (GRCm39) probably benign Het
Prdm13 G A 4: 21,679,125 (GRCm39) A455V possibly damaging Het
Ptpn13 A T 5: 103,739,101 (GRCm39) Y2289F probably damaging Het
Ptpn18 G T 1: 34,498,966 (GRCm39) R21L probably benign Het
Ptprd A G 4: 75,916,736 (GRCm39) probably null Het
Rcn3 G T 7: 44,733,095 (GRCm39) D258E probably damaging Het
Ro60 C T 1: 143,641,170 (GRCm39) probably null Het
Rsf1 GCG GCGACGGCGCCG 7: 97,229,114 (GRCm39) probably benign Het
Sacs T A 14: 61,429,895 (GRCm39) H651Q probably benign Het
Sacs T C 14: 61,448,702 (GRCm39) S3583P probably damaging Het
Scel A G 14: 103,829,807 (GRCm39) N463S possibly damaging Het
Serpinb2 A T 1: 107,443,284 (GRCm39) I28F possibly damaging Het
Sin3b A G 8: 73,473,131 (GRCm39) K484E probably benign Het
Snrnp48 T A 13: 38,400,397 (GRCm39) V168D probably damaging Het
Snx18 T G 13: 113,754,931 (GRCm39) M1L probably benign Het
Spata31h1 T C 10: 82,131,295 (GRCm39) N572D probably benign Het
Srcap T A 7: 127,158,204 (GRCm39) N2693K unknown Het
Stim1 A G 7: 102,078,014 (GRCm39) D172G Het
Stip1 A T 19: 7,002,687 (GRCm39) L414H probably damaging Het
Sun1 A G 5: 139,209,390 (GRCm39) H40R probably damaging Het
Sva T A 6: 42,019,182 (GRCm39) D117E possibly damaging Het
Syne2 A G 12: 75,943,444 (GRCm39) D321G probably damaging Het
Trim45 A G 3: 100,835,394 (GRCm39) D459G probably damaging Het
Ttc6 G A 12: 57,697,790 (GRCm39) W43* probably null Het
Ugt2b35 A G 5: 87,152,780 (GRCm39) T317A possibly damaging Het
Usp32 C T 11: 84,916,370 (GRCm39) R858Q probably damaging Het
Vmn2r53 G T 7: 12,334,752 (GRCm39) Q303K probably benign Het
Yeats2 T C 16: 19,969,312 (GRCm39) probably null Het
Zfp804a A G 2: 82,088,747 (GRCm39) N859D probably benign Het
Zscan10 A T 17: 23,824,580 (GRCm39) Q12L 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
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
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'- TCGTGATGTTGAGCCACAG -3'
(R):5'- TGGTTAGAACTGCAGGCCTG -3'

Sequencing Primer
(F):5'- AAGTGCCTCCATGTACTC -3'
(R):5'- ATCAATGACCAGGACCTCTTTC -3'
Posted On 2021-08-02