Incidental Mutation 'R4832:Map3k4'
ID 372946
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 042448-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.953) question?
Stock # R4832 (G1)
Quality Score 225
Status Validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 12490667 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Lysine at position 255 (E255K)
Ref Sequence ENSEMBL: ENSMUSP00000086459 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect probably damaging
Transcript: ENSMUST00000089058
AA Change: E255K

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: E255K

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 0.1638 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.8%
  • 20x: 93.9%
Validation Efficiency 98% (106/108)
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: 98 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110032F04Rik T C 3: 68,777,597 (GRCm39) V186A possibly damaging Het
1700088E04Rik A T 15: 79,019,409 (GRCm39) M198K probably damaging Het
4933402J07Rik A G 8: 88,294,601 (GRCm39) K84R probably null Het
Aamdc T C 7: 97,199,773 (GRCm39) probably null Het
Abcc9 A G 6: 142,617,282 (GRCm39) V594A probably damaging Het
Adamts13 G A 2: 26,879,414 (GRCm39) D656N probably benign Het
Adcy10 G T 1: 165,334,213 (GRCm39) C122F probably damaging Het
Adi1 A G 12: 28,725,252 (GRCm39) M1V probably null Het
Ahnak G A 19: 8,989,824 (GRCm39) probably benign Het
Akt1 G T 12: 112,623,521 (GRCm39) P313Q probably damaging Het
Ano3 A T 2: 110,498,067 (GRCm39) M758K probably damaging Het
Baz2a T A 10: 127,958,999 (GRCm39) N1168K probably benign Het
Bbs10 A G 10: 111,136,995 (GRCm39) K703E probably benign Het
Bcap29 A G 12: 31,674,202 (GRCm39) I131T probably benign Het
Brd10 G T 19: 29,694,616 (GRCm39) L1626I possibly damaging Het
Btnl6 T C 17: 34,732,966 (GRCm39) D299G possibly damaging Het
Ccdc66 A G 14: 27,222,524 (GRCm39) I73T probably benign Het
Cdh2 A G 18: 16,760,754 (GRCm39) S538P probably benign Het
Cfap54 T A 10: 92,803,390 (GRCm39) M1551L probably benign Het
Chd2 G A 7: 73,151,873 (GRCm39) A243V probably damaging Het
Cntnap1 T A 11: 101,073,845 (GRCm39) N665K probably damaging Het
Colgalt2 C T 1: 152,360,749 (GRCm39) T262I possibly damaging Het
Cyp24a1 T C 2: 170,338,098 (GRCm39) I149V probably benign Het
Cyp2a5 T A 7: 26,534,970 (GRCm39) probably null Het
Dab2 A G 15: 6,366,080 (GRCm39) probably null Het
Dnah17 T A 11: 117,917,606 (GRCm39) I4158F probably damaging Het
Dnm2 G A 9: 21,385,975 (GRCm39) probably null Het
Dpp7 A T 2: 25,242,398 (GRCm39) probably benign Het
Epha6 T A 16: 59,780,776 (GRCm39) I642F probably damaging Het
Erbb4 T C 1: 68,369,397 (GRCm39) S415G probably benign Het
Fancd2 A G 6: 113,530,683 (GRCm39) T439A probably benign Het
Fat1 G A 8: 45,466,102 (GRCm39) V1431M possibly damaging Het
Fhod3 G A 18: 25,223,305 (GRCm39) A884T probably benign Het
Fsip2 A G 2: 82,820,515 (GRCm39) D5416G possibly damaging Het
Gabarap C T 11: 69,882,678 (GRCm39) probably benign Het
Garre1 T C 7: 33,938,333 (GRCm39) probably benign Het
Gm11544 C T 11: 94,736,532 (GRCm39) noncoding transcript Het
Gnat2 A C 3: 108,007,964 (GRCm39) K304Q probably benign Het
Gpr141b T A 13: 19,913,840 (GRCm39) noncoding transcript Het
Gramd4 C T 15: 86,019,057 (GRCm39) A575V probably benign Het
Gtpbp10 G A 5: 5,589,295 (GRCm39) A274V possibly damaging Het
Gzmb A G 14: 56,497,679 (GRCm39) I187T probably damaging Het
H2-M10.2 G A 17: 36,595,219 (GRCm39) T315I probably damaging Het
Haus5 A T 7: 30,356,452 (GRCm39) F524I probably damaging Het
Herc1 A G 9: 66,403,253 (GRCm39) S4391G probably benign Het
Herc2 T A 7: 55,748,165 (GRCm39) L511* probably null Het
Htt T A 5: 34,982,184 (GRCm39) C923S probably benign Het
Idua T C 5: 108,817,247 (GRCm39) S7P probably benign Het
Ighv16-1 A T 12: 114,032,466 (GRCm39) L112Q probably damaging Het
Igkv1-110 A G 6: 68,248,185 (GRCm39) K98R probably benign Het
Kif15 G A 9: 122,831,191 (GRCm39) probably null Het
Leng9 C A 7: 4,152,029 (GRCm39) G216W probably damaging Het
Lrpprc A G 17: 85,014,584 (GRCm39) L1306S probably benign Het
Lztfl1 C A 9: 123,544,454 (GRCm39) E20D possibly damaging Het
Maob T C X: 16,582,662 (GRCm39) T400A probably benign Het
Megf9 G A 4: 70,452,665 (GRCm39) T132M probably damaging Het
Mob4 T C 1: 55,184,411 (GRCm39) probably benign Het
Mttp G A 3: 137,821,811 (GRCm39) A252V probably benign Het
Mxi1 A G 19: 53,358,745 (GRCm39) D226G probably damaging Het
Myh14 A G 7: 44,274,566 (GRCm39) S1249P probably benign Het
Mylk G A 16: 34,742,737 (GRCm39) G1083D probably benign Het
Mylk4 T G 13: 32,905,960 (GRCm39) I408L probably benign Het
Nbas A G 12: 13,533,740 (GRCm39) S1792G probably benign Het
Nelfb A G 2: 25,099,981 (GRCm39) V212A probably damaging Het
Nisch T C 14: 30,899,587 (GRCm39) probably benign Het
Nqo1 C G 8: 108,115,477 (GRCm39) D267H probably benign Het
Or8u10 C A 2: 85,915,190 (GRCm39) L310F probably benign Het
Pcid2 T A 8: 13,135,425 (GRCm39) I195F probably damaging Het
Pcnx2 A T 8: 126,478,927 (GRCm39) M2107K probably damaging Het
Pgd A T 4: 149,241,048 (GRCm39) probably benign Het
Prim2 T C 1: 33,503,145 (GRCm39) M430V probably benign Het
Prkaa1 A G 15: 5,190,101 (GRCm39) T40A probably damaging Het
Ptges T C 2: 30,793,232 (GRCm39) probably benign Het
Ptprn T C 1: 75,234,909 (GRCm39) E226G probably benign Het
Rab14 A G 2: 35,079,978 (GRCm39) F55S probably damaging Het
Ralgps2 A T 1: 156,684,637 (GRCm39) probably benign Het
Rgs11 C T 17: 26,426,542 (GRCm39) H258Y probably benign Het
Rhpn2 T C 7: 35,075,774 (GRCm39) probably null Het
Rprd2 A T 3: 95,681,483 (GRCm39) V452E probably damaging Het
Scube3 C A 17: 28,384,989 (GRCm39) H646Q probably damaging Het
Selp A T 1: 163,953,909 (GRCm39) I70F probably damaging Het
Septin2 A G 1: 93,426,849 (GRCm39) I153V probably damaging Het
Sh3rf3 G A 10: 58,649,905 (GRCm39) S170N probably benign Het
Skint4 A T 4: 112,000,963 (GRCm39) I353F possibly damaging Het
Slc16a12 A G 19: 34,657,780 (GRCm39) I41T possibly damaging Het
Snai2 T C 16: 14,524,881 (GRCm39) F129S probably damaging Het
Top3b C T 16: 16,708,526 (GRCm39) R629* probably null Het
Trim17 T A 11: 58,862,270 (GRCm39) V434E probably damaging Het
Ttn G A 2: 76,615,327 (GRCm39) P15051L probably damaging Het
Uggt2 A T 14: 119,239,259 (GRCm39) I1391N probably damaging Het
Usp8 A T 2: 126,596,958 (GRCm39) M923L probably damaging Het
Vmn1r176 T C 7: 23,534,463 (GRCm39) H230R possibly damaging Het
Vmn1r217 C A 13: 23,298,159 (GRCm39) D248Y probably damaging Het
Vmn2r14 A T 5: 109,363,976 (GRCm39) C647S probably damaging Het
Vwa5b1 A G 4: 138,332,851 (GRCm39) I237T probably damaging Het
Zan T A 5: 137,391,423 (GRCm39) D4687V unknown Het
Zfp273 T C 13: 67,973,484 (GRCm39) V204A probably benign Het
Zfp956 T G 6: 47,928,987 (GRCm39) 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
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 12,451,301 (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'- TTGAAACCGGCTCCATTGC -3'
(R):5'- CAATAAGCCTTACCTCAGTCTCGG -3'

Sequencing Primer
(F):5'- TTGCTGGAGAAGGCAATGCTC -3'
(R):5'- TGTAGCAATGCCAAGCTGC -3'
Posted On 2016-03-01