Mutagenetix > Incidental Mutation

Incidental Mutation 'R8294:Map3k4'

638872

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

067784-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.953) question?

Stock #

R8294 (G1)

Quality Score

193.009

Status

Validated

Chromosome

Chromosomal Location

12446508-12537683 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 12537500 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Serine at position 6 (A6S)

Ref Sequence

ENSEMBL: ENSMUSP00000086459 (fasta)

Gene Model

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

AlphaFold

O08648

Predicted Effect

unknown
Transcript: ENSMUST00000089058
AA Change: A6S

SMART Domains

Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: A6S

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

0.0693

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

98% (42/43)

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: 44 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca4	T	C	3: 121,897,217 (GRCm39)	V632A	possibly damaging	Het
Abcf2	CAT	CATAAT	5: 24,781,589 (GRCm39)		probably benign	Het
Acat2	T	C	17: 13,175,243 (GRCm39)	I79V	probably benign	Het
Arid3a	A	T	10: 79,786,535 (GRCm39)		silent	Het
Cecr2	C	T	6: 120,710,747 (GRCm39)	A154V	probably damaging	Het
Cog3	A	C	14: 75,954,619 (GRCm39)	L650R	probably damaging	Het
Col12a1	A	T	9: 79,606,594 (GRCm39)	F610I	possibly damaging	Het
Col24a1	A	G	3: 145,186,844 (GRCm39)	D1215G	probably null	Het
Ctsh	C	G	9: 89,950,489 (GRCm39)	A219G	possibly damaging	Het
Dnah10	C	T	5: 124,859,410 (GRCm39)	L2126F	probably damaging	Het
Dock10	A	G	1: 80,488,079 (GRCm39)	V2028A	possibly damaging	Het
Ece1	T	C	4: 137,675,931 (GRCm39)	V435A	possibly damaging	Het
Epha8	G	T	4: 136,665,897 (GRCm39)	L420M	probably damaging	Het
H4c1	A	G	13: 23,944,957 (GRCm39)	F62L	probably damaging	Het
Hk1	T	G	10: 62,131,624 (GRCm39)	I245L	probably benign	Het
Hyal6	A	C	6: 24,734,378 (GRCm39)	K104Q	possibly damaging	Het
Kalrn	T	C	16: 33,853,954 (GRCm39)	I2017V	probably benign	Het
Khdc4	C	T	3: 88,603,915 (GRCm39)	A244V	probably damaging	Het
Krt72	A	T	15: 101,694,472 (GRCm39)	L141Q	probably damaging	Het
Muc6	T	C	7: 141,217,263 (GRCm39)	Y2470C	possibly damaging	Het
Nrip1	A	G	16: 76,089,418 (GRCm39)	V713A	probably damaging	Het
Or10q1b	A	G	19: 13,683,010 (GRCm39)	D273G	probably benign	Het
Or11g26	A	G	14: 50,753,083 (GRCm39)	T141A	possibly damaging	Het
Or2ah1	T	A	2: 85,653,531 (GRCm39)	I72N	probably damaging	Het
Or6aa1	T	C	7: 86,044,487 (GRCm39)	Y73C	probably damaging	Het
Paip1	C	T	13: 119,587,300 (GRCm39)	T304I	possibly damaging	Het
Pde4dip	A	G	3: 97,674,694 (GRCm39)	L74P	probably damaging	Het
Prkch	T	A	12: 73,806,484 (GRCm39)	L577H	probably damaging	Het
Rp1	A	G	1: 4,416,220 (GRCm39)	S1631P	probably benign	Het
Rph3a	A	G	5: 121,099,429 (GRCm39)	F154S	probably damaging	Het
S1pr5	A	G	9: 21,156,300 (GRCm39)	V42A	possibly damaging	Het
Scaper	G	A	9: 55,517,280 (GRCm39)	L1052F	possibly damaging	Het
Slc44a2	G	T	9: 21,259,643 (GRCm39)	V597F	probably damaging	Het
Srsf1	T	A	11: 87,939,467 (GRCm39)	S116T	probably benign	Het
Ssh2	A	G	11: 77,345,027 (GRCm39)	D1004G	probably benign	Het
St3gal5	T	A	6: 72,074,816 (GRCm39)	D25E		Het
Syt17	A	T	7: 118,009,228 (GRCm39)	Y327N	probably damaging	Het
T	T	A	17: 8,653,364 (GRCm39)	M1K	probably null	Het
Tmem201	A	T	4: 149,815,554 (GRCm39)	I132N	possibly damaging	Het
Tmprss15	A	T	16: 78,868,176 (GRCm39)	C211S	probably benign	Het
Trim36	T	C	18: 46,331,588 (GRCm39)	D7G	probably benign	Het
Trip11	T	A	12: 101,811,160 (GRCm39)	K1863N	possibly damaging	Het
Vmn2r13	A	T	5: 109,322,978 (GRCm39)	S104T	probably benign	Het
Zfp977	T	C	7: 42,229,689 (GRCm39)	T279A	probably benign	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
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
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'- AGCACTACTGCAAAGGCCAG -3'
(R):5'- ACCTGATTTACCACTGGCC -3'

Sequencing Primer
(F):5'- TACTGCAAAGGCCAGGGTCG -3'
(R):5'- CCGTAGCCCAGCGTTCG -3'

Posted On

2020-07-28