Mutagenetix > Incidental Mutation

Incidental Mutation 'R6644:Map3k4'

526041

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

044765-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.958) question?

Stock #

R6644 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

12446508-12537683 bp(-) (GRCm39)

Type of Mutation

critical splice donor site (2 bp from exon)

DNA Base Change (assembly)

A to G at 12451297 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000086459 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000089058]

AlphaFold

O08648

Predicted Effect

probably null
Transcript: ENSMUST00000089058

SMART Domains

Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426

Domain	Start	End	E-Value	Type
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

0.9497

Coding Region Coverage

1x: 99.9%
3x: 99.5%
10x: 97.5%
20x: 92.3%

Validation Efficiency

100% (50/50)

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: 50 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca7	C	T	10: 79,844,598 (GRCm39)	P1461L	probably damaging	Het
Abhd14a	T	C	9: 106,321,472 (GRCm39)	Y10C	probably damaging	Het
Adcy2	C	T	13: 68,816,671 (GRCm39)	V772M	possibly damaging	Het
Apob	A	G	12: 8,059,077 (GRCm39)	M2487V	probably damaging	Het
B4galnt1	T	C	10: 127,007,662 (GRCm39)		probably null	Het
Cabp7	C	T	11: 4,690,396 (GRCm39)	V76I	probably benign	Het
Cbr3	A	G	16: 93,487,399 (GRCm39)	Y194C	probably damaging	Het
Cdk18	G	A	1: 132,049,807 (GRCm39)	Q58*	probably null	Het
Cryba4	T	C	5: 112,394,628 (GRCm39)	D167G	probably damaging	Het
Czib	T	G	4: 107,752,119 (GRCm39)	I130S	probably damaging	Het
Dner	T	C	1: 84,373,428 (GRCm39)	N588S	probably damaging	Het
Dnm1l	T	C	16: 16,147,737 (GRCm39)	I343V	probably benign	Het
Eif1ad16	A	G	12: 87,985,460 (GRCm39)	F28L	probably benign	Het
Fam168b	C	A	1: 34,875,822 (GRCm39)	G21V	probably damaging	Het
Fbxw17	G	A	13: 50,577,255 (GRCm39)	R49Q	probably damaging	Het
Garin2	T	A	12: 78,762,060 (GRCm39)	D241E	probably damaging	Het
Gm10332	T	A	14: 55,057,616 (GRCm39)	F59I	probably damaging	Het
Gnai3	A	G	3: 108,030,852 (GRCm39)		probably null	Het
Helz	T	A	11: 107,523,087 (GRCm39)	M75K	possibly damaging	Het
Hnrnph3	C	T	10: 62,854,672 (GRCm39)		probably benign	Het
Ifi211	C	T	1: 173,733,118 (GRCm39)	C181Y	probably benign	Het
Immp1l	A	G	2: 105,767,390 (GRCm39)	K83R	probably damaging	Het
Itga6	G	A	2: 71,671,468 (GRCm39)	G740R	probably damaging	Het
Klhl1	T	C	14: 96,755,354 (GRCm39)	T134A	probably benign	Het
Klhl7	A	G	5: 24,354,244 (GRCm39)	D353G	probably damaging	Het
Map3k1	A	G	13: 111,888,983 (GRCm39)	S1325P	probably benign	Het
Meioc	G	A	11: 102,559,286 (GRCm39)		probably null	Het
Mfap5	T	C	6: 122,497,555 (GRCm39)	F26L	probably damaging	Het
Myo5a	A	G	9: 75,054,249 (GRCm39)	T386A	probably damaging	Het
Npc1l1	A	T	11: 6,164,013 (GRCm39)	L1266Q	probably damaging	Het
Npc1l1	G	T	11: 6,164,014 (GRCm39)	L1266M	probably damaging	Het
Or4c116	A	G	2: 88,942,325 (GRCm39)	M177T	probably benign	Het
Or51aa2	C	A	7: 103,188,265 (GRCm39)	V59F	possibly damaging	Het
Pbld1	T	A	10: 62,910,842 (GRCm39)	S233T	probably damaging	Het
Phf12	A	G	11: 77,916,918 (GRCm39)	*789W	probably null	Het
Sf3b2	A	T	19: 5,329,992 (GRCm39)		probably null	Het
Slc23a3	A	G	1: 75,105,191 (GRCm39)	I459T	probably damaging	Het
Spata31e4	A	G	13: 50,856,071 (GRCm39)	T570A	possibly damaging	Het
Sptbn2	C	G	19: 4,799,040 (GRCm39)	R2037G	probably benign	Het
Stard9	A	C	2: 120,526,253 (GRCm39)	M837L	probably benign	Het
Stx5a	A	T	19: 8,732,612 (GRCm39)		probably benign	Het
Tmc7	A	G	7: 118,137,385 (GRCm39)	V719A	probably benign	Het
Trank1	T	A	9: 111,193,902 (GRCm39)	I642K	possibly damaging	Het
Trim34a	T	C	7: 103,910,244 (GRCm39)	Y349H	probably damaging	Het
Uba7	A	G	9: 107,858,671 (GRCm39)	Y834C	possibly damaging	Het
Ube2d1	A	G	10: 71,092,530 (GRCm39)	S105P	possibly damaging	Het
Vps13a	A	G	19: 16,722,283 (GRCm39)	V343A	possibly damaging	Het
Zbtb37	G	A	1: 160,859,643 (GRCm39)	Q221*	probably null	Het
Zfp119b	T	C	17: 56,246,148 (GRCm39)	N346S	probably benign	Het
Zfp708	G	T	13: 67,218,785 (GRCm39)	T358K	possibly damaging	Het

Other mutations in Map3k4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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'- TGATCCCTCTGGAGTTGTCC -3'
(R):5'- TGCTGAGGAGTAACAACATATTGC -3'

Sequencing Primer
(F):5'- AGTGCGGGATAAAGCTCTCC -3'
(R):5'- GGAGTAACAACATATTGCTTGGTGC -3'

Posted On

2018-06-22