Incidental Mutation 'R1542:Map3k4'
ID 171871
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 039581-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.958) question?
Stock # R1542 (G1)
Quality Score 218
Status Not validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 12454793 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Proline at position 1399 (L1399P)
Ref Sequence ENSEMBL: ENSMUSP00000086459 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect probably damaging
Transcript: ENSMUST00000089058
AA Change: L1399P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: L1399P

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: 99.1%
  • 3x: 98.3%
  • 10x: 96.3%
  • 20x: 92.5%
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: 92 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700006A11Rik A G 3: 124,208,055 (GRCm39) M208T possibly damaging Het
Acsbg2 T A 17: 57,156,791 (GRCm39) I416F probably damaging Het
Adam6b G A 12: 113,454,559 (GRCm39) D459N possibly damaging Het
Adprh A T 16: 38,266,286 (GRCm39) D285E probably damaging Het
Aggf1 A T 13: 95,507,450 (GRCm39) C112S probably benign Het
Als2cl T C 9: 110,723,102 (GRCm39) V602A probably benign Het
Angptl2 G T 2: 33,118,897 (GRCm39) V224F probably benign Het
Ap3b2 A T 7: 81,127,825 (GRCm39) probably null Het
Aqp2 A C 15: 99,481,723 (GRCm39) I206L probably benign Het
Asap2 A G 12: 21,315,998 (GRCm39) D930G probably damaging Het
Cacna1e T A 1: 154,353,525 (GRCm39) M682L probably benign Het
Ccdc18 A G 5: 108,360,054 (GRCm39) N1146S probably benign Het
Ccr4 G A 9: 114,321,073 (GRCm39) H331Y probably benign Het
Cd33 A G 7: 43,181,530 (GRCm39) L210P probably damaging Het
Cep85l T C 10: 53,177,680 (GRCm39) E351G probably damaging Het
Cntn6 C A 6: 104,825,061 (GRCm39) T867K probably damaging Het
Cpeb2 C T 5: 43,443,218 (GRCm39) R970C probably damaging Het
Cul7 T A 17: 46,974,116 (GRCm39) L1467H probably damaging Het
Dscaml1 T A 9: 45,660,738 (GRCm39) I1693K possibly damaging Het
Ebf4 A T 2: 130,207,418 (GRCm39) M621L probably benign Het
Elp4 G T 2: 105,624,954 (GRCm39) T313N probably benign Het
Epas1 T A 17: 87,131,918 (GRCm39) I373N possibly damaging Het
Etnk1 A T 6: 143,126,367 (GRCm39) M71L probably benign Het
Fry C T 5: 150,328,431 (GRCm39) T1257I probably benign Het
Gm21834 A G 17: 58,048,946 (GRCm39) F90S possibly damaging Het
Gm8674 T A 13: 50,054,039 (GRCm39) noncoding transcript Het
Gna11 T C 10: 81,369,162 (GRCm39) T134A probably benign Het
Golga5 C T 12: 102,440,979 (GRCm39) S238F probably damaging Het
Grin2a T A 16: 9,397,067 (GRCm39) N1007Y probably damaging Het
H3c6 A G 13: 23,746,338 (GRCm39) F68L probably damaging Het
Ifnar2 G A 16: 91,196,153 (GRCm39) V253M possibly damaging Het
Insl5 A T 4: 102,875,382 (GRCm39) S123T probably damaging Het
Itgb2 T C 10: 77,395,320 (GRCm39) S474P probably benign Het
Kcnb2 A G 1: 15,781,012 (GRCm39) H628R probably benign Het
L3mbtl2 G A 15: 81,566,352 (GRCm39) D392N probably null Het
Lrp1b G T 2: 41,013,724 (GRCm39) T1813K probably damaging Het
Mbtps1 A C 8: 120,272,986 (GRCm39) probably null Het
Mettl25 A T 10: 105,661,981 (GRCm39) S330T probably benign Het
Mical2 T C 7: 111,908,675 (GRCm39) L211P probably damaging Het
Mmrn1 T A 6: 60,922,102 (GRCm39) S186R probably damaging Het
Mob3b C A 4: 35,084,046 (GRCm39) V48L possibly damaging Het
Napsa A T 7: 44,231,113 (GRCm39) H114L probably damaging Het
Nsmce4a A T 7: 130,147,623 (GRCm39) probably null Het
Nup62 A G 7: 44,479,353 (GRCm39) K456R possibly damaging Het
Nwd2 T A 5: 63,964,318 (GRCm39) W1301R probably damaging Het
Oprm1 G T 10: 6,738,960 (GRCm39) W29L probably damaging Het
Or10al2 A T 17: 37,983,142 (GRCm39) E76V probably damaging Het
Or1l4b T A 2: 37,036,978 (GRCm39) S251R probably damaging Het
Or2c1 T A 16: 3,657,696 (GRCm39) N286K probably damaging Het
Or5w17 A G 2: 87,583,662 (GRCm39) V225A probably damaging Het
Pals2 A G 6: 50,175,306 (GRCm39) Y539C probably damaging Het
Pcnt T G 10: 76,225,221 (GRCm39) N1761T probably benign Het
Pcnt C T 10: 76,237,220 (GRCm39) M1355I probably benign Het
Pde11a A T 2: 75,877,199 (GRCm39) S757T probably benign Het
Pde6a T A 18: 61,390,116 (GRCm39) I490N possibly damaging Het
Pgap1 A G 1: 54,531,249 (GRCm39) V742A probably benign Het
Pik3c2b T C 1: 133,017,772 (GRCm39) L915P probably damaging Het
Pkd1l1 A G 11: 8,824,179 (GRCm39) C1129R possibly damaging Het
Pkhd1l1 A T 15: 44,391,587 (GRCm39) H1551L probably benign Het
Plxnb2 C T 15: 89,050,124 (GRCm39) C491Y probably damaging Het
Ppt1 C A 4: 122,751,402 (GRCm39) H300N probably benign Het
Prpf3 T A 3: 95,743,782 (GRCm39) Q457L probably benign Het
Ranbp17 C T 11: 33,214,672 (GRCm39) V914I probably benign Het
Rasal2 T C 1: 157,003,421 (GRCm39) I413V possibly damaging Het
Rb1cc1 G A 1: 6,314,473 (GRCm39) V382I possibly damaging Het
Rere T A 4: 150,700,399 (GRCm39) F1125I probably damaging Het
Rprd2 A T 3: 95,672,988 (GRCm39) V805E possibly damaging Het
Septin10 T G 10: 59,002,428 (GRCm39) E162A probably damaging Het
Septin12 G T 16: 4,810,159 (GRCm39) D125E probably benign Het
Serpina6 A G 12: 103,620,732 (GRCm39) Y6H probably benign Het
Serpinb3c T C 1: 107,200,517 (GRCm39) M209V probably damaging Het
Slc2a7 A T 4: 150,252,928 (GRCm39) T523S probably damaging Het
Smdt1 T C 15: 82,230,376 (GRCm39) V31A possibly damaging Het
Snrnp48 T C 13: 38,404,680 (GRCm39) I245T probably damaging Het
Spink2 G A 5: 77,354,812 (GRCm39) T33I probably damaging Het
Sptan1 A G 2: 29,917,139 (GRCm39) T2204A probably damaging Het
Synj2 A G 17: 6,075,292 (GRCm39) D306G probably benign Het
Tas2r109 A G 6: 132,957,873 (GRCm39) I19T possibly damaging Het
Tbk1 C T 10: 121,395,840 (GRCm39) V418M probably benign Het
Tcerg1 A G 18: 42,686,495 (GRCm39) E684G probably damaging Het
Tenm2 T C 11: 36,191,047 (GRCm39) N308S probably damaging Het
Tfb2m A T 1: 179,365,426 (GRCm39) probably null Het
Tmc1 T A 19: 20,793,486 (GRCm39) L558F probably damaging Het
Tmprss5 T A 9: 49,020,434 (GRCm39) I80N possibly damaging Het
Trappc2l G A 8: 123,342,146 (GRCm39) V131M probably damaging Het
Trpm7 A C 2: 126,664,519 (GRCm39) Y953* probably null Het
Ttn T C 2: 76,583,859 (GRCm39) R22383G probably damaging Het
Ugt1a6b G A 1: 88,034,983 (GRCm39) G107D probably benign Het
Vmn1r197 A T 13: 22,512,520 (GRCm39) Y147F probably benign Het
Zfp507 A T 7: 35,494,226 (GRCm39) N272K possibly damaging Het
Zfp526 G A 7: 24,925,687 (GRCm39) E649K probably benign Het
Zswim6 G A 13: 107,863,769 (GRCm39) noncoding transcript 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
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 12,451,301 (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'- CAACGAGTATCTCGGAGCAGCAAG -3'
(R):5'- ACAGTCATAGAGTCCAGAAGCGACC -3'

Sequencing Primer
(F):5'- CGGCAAAGTGGCTGTCAG -3'
(R):5'- CTGTGTTGACCAACTGTGAGAC -3'
Posted On 2014-04-13