Incidental Mutation 'R1446:Map3k4'
ID 158910
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 039501-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.953) question?
Stock # R1446 (G1)
Quality Score 225
Status Not validated
Chromosome 17
Chromosomal Location 12446508-12537683 bp(-) (GRCm39)
Type of Mutation nonsense
DNA Base Change (assembly) T to A at 12475681 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Stop codon at position 84 (L84*)
Gene Model predicted gene model for transcript(s): [ENSMUST00000089058]
AlphaFold O08648
Predicted Effect probably null
Transcript: ENSMUST00000089058
AA Change: K805*
SMART Domains Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: K805*

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
Predicted Effect probably null
Transcript: ENSMUST00000115691
AA Change: L84*
SMART Domains Protein: ENSMUSP00000111355
Gene: ENSMUSG00000079716
AA Change: L84*

DomainStartEndE-ValueType
low complexity region 50 69 N/A INTRINSIC
low complexity region 83 100 N/A INTRINSIC
low complexity region 106 122 N/A INTRINSIC
Coding Region Coverage
  • 1x: 99.0%
  • 3x: 98.0%
  • 10x: 95.3%
  • 20x: 89.6%
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: 72 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aasdh C T 5: 77,034,136 (GRCm39) A472T probably benign Het
Adcy4 A T 14: 56,007,480 (GRCm39) probably null Het
Ahcyl2 T C 6: 29,891,239 (GRCm39) S448P probably damaging Het
Anks1b A G 10: 90,346,935 (GRCm39) Y745C probably benign Het
Anxa1 A T 19: 20,351,103 (GRCm39) L339Q probably damaging Het
Apoa4 A G 9: 46,153,591 (GRCm39) D64G probably benign Het
Arpc1a A G 5: 145,037,896 (GRCm39) probably null Het
Bank1 C T 3: 135,769,904 (GRCm39) G727R probably damaging Het
Best2 T C 8: 85,734,593 (GRCm39) Q375R probably benign Het
Cacna1b T A 2: 24,596,189 (GRCm39) M501L probably benign Het
Col27a1 T A 4: 63,143,040 (GRCm39) Y243N probably damaging Het
Cyp11a1 A T 9: 57,922,560 (GRCm39) Q80L possibly damaging Het
Dnah10 T A 5: 124,866,860 (GRCm39) W2260R probably damaging Het
Dnajc19 T C 3: 34,112,128 (GRCm39) H139R probably benign Het
Dppa5a T A 9: 78,275,071 (GRCm39) N77I probably benign Het
Edc4 T C 8: 106,614,764 (GRCm39) S125P probably damaging Het
Eid2 T C 7: 27,968,014 (GRCm39) I212T possibly damaging Het
Fam234b T A 6: 135,186,328 (GRCm39) probably null Het
Frem2 T C 3: 53,562,017 (GRCm39) E830G probably benign Het
Fyb1 A T 15: 6,681,947 (GRCm39) I765L probably benign Het
Fyn T G 10: 39,398,775 (GRCm39) S124A probably benign Het
Gal3st3 T A 19: 5,356,939 (GRCm39) F105I probably damaging Het
Gpr146 A G 5: 139,379,177 (GRCm39) I326M probably benign Het
Grk2 G A 19: 4,337,437 (GRCm39) R617C possibly damaging Het
Gsn A G 2: 35,196,598 (GRCm39) K669R probably benign Het
H2-T10 A T 17: 36,430,266 (GRCm39) I225N possibly damaging Het
Il12rb2 T C 6: 67,286,127 (GRCm39) H106R probably benign Het
Kat14 A G 2: 144,215,638 (GRCm39) E41G probably damaging Het
Kcnma1 G T 14: 23,361,792 (GRCm39) T1006K probably damaging Het
Kif18b G A 11: 102,805,525 (GRCm39) T244I probably damaging Het
Klb A T 5: 65,506,338 (GRCm39) H195L probably damaging Het
Lrriq4 T C 3: 30,704,727 (GRCm39) F252L probably benign Het
Lum C T 10: 97,404,252 (GRCm39) T49I possibly damaging Het
Mindy2 A G 9: 70,514,738 (GRCm39) probably null Het
Mpped2 G T 2: 106,614,077 (GRCm39) R137L possibly damaging Het
Myo18b G A 5: 112,905,425 (GRCm39) R2058W probably damaging Het
Nol8 T A 13: 49,808,703 (GRCm39) L65Q probably damaging Het
Or11g27 T C 14: 50,771,159 (GRCm39) S97P possibly damaging Het
Or4c108 A G 2: 88,804,109 (GRCm39) I42T probably benign Het
Or4x6 A T 2: 89,949,202 (GRCm39) L247M probably damaging Het
Or5b105 G A 19: 13,080,380 (GRCm39) A96V possibly damaging Het
Or5g9 A G 2: 85,551,917 (GRCm39) H56R probably damaging Het
Or8b3 T G 9: 38,314,601 (GRCm39) C144G possibly damaging Het
Or9a4 C T 6: 40,548,833 (GRCm39) S171L probably benign Het
Parp12 G T 6: 39,079,495 (GRCm39) D338E probably benign Het
Pde6d T C 1: 86,474,414 (GRCm39) E77G probably damaging Het
Phkg1 A C 5: 129,902,055 (GRCm39) probably null Het
Pigw A C 11: 84,769,186 (GRCm39) S48A probably benign Het
Pkm T A 9: 59,576,193 (GRCm39) probably null Het
Ppp1r3f G A X: 7,426,602 (GRCm39) T553M probably damaging Het
Retreg2 T A 1: 75,120,103 (GRCm39) F44L possibly damaging Het
Ryr2 A T 13: 11,753,035 (GRCm39) M1762K probably benign Het
Sec16a A G 2: 26,313,579 (GRCm39) V1927A probably benign Het
Sec23a G T 12: 59,025,345 (GRCm39) A492E probably damaging Het
Skint4 T A 4: 111,975,311 (GRCm39) H82Q probably benign Het
Srbd1 T C 17: 86,446,580 (GRCm39) K60E probably benign Het
Stk24 A G 14: 121,545,456 (GRCm39) Y101H probably damaging Het
Sult1e1 A T 5: 87,726,396 (GRCm39) N239K probably damaging Het
Tgs1 C T 4: 3,604,848 (GRCm39) P757S probably damaging Het
Tmc2 A T 2: 130,090,650 (GRCm39) E665D probably damaging Het
Tmprss15 C A 16: 78,875,846 (GRCm39) D163Y probably benign Het
Unc13a C A 8: 72,101,625 (GRCm39) V1009L possibly damaging Het
Unc45b G T 11: 82,819,496 (GRCm39) G490C probably damaging Het
Vmn1r177 T A 7: 23,565,765 (GRCm39) H37L probably damaging Het
Vwa5a A G 9: 38,645,264 (GRCm39) M450V possibly damaging Het
Wars2 T C 3: 99,094,843 (GRCm39) I46T probably benign Het
Wdfy3 G T 5: 101,999,176 (GRCm39) T3098K possibly damaging Het
Zan A T 5: 137,387,622 (GRCm39) I4863N unknown Het
Zfp616 A G 11: 73,974,064 (GRCm39) probably null Het
Zfp770 A T 2: 114,027,514 (GRCm39) I185N probably damaging Het
Zfp808 T G 13: 62,320,821 (GRCm39) H683Q probably damaging Het
Zmym4 A T 4: 126,776,275 (GRCm39) W1221R probably 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
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 12,451,301 (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'- GCACGGGCTTCACCTTAACATACTG -3'
(R):5'- GGCAGCGTATTTGGGCACATTC -3'

Sequencing Primer
(F):5'- TGCTTTCAGAGCGTCCAG -3'
(R):5'- CGTATTTGGGCACATTCTCAGTAAC -3'
Posted On 2014-03-14