Mutagenetix > Incidental Mutation

Incidental Mutation 'R4956:Map3k8'

381609

Institutional Source

Beutler Lab

Gene Symbol

Map3k8

Ensembl Gene

ENSMUSG00000024235

Gene Name

mitogen-activated protein kinase kinase kinase 8

Synonyms

Tpl2, Cot, Cot/Tpl2, Tpl-2, c-COT

MMRRC Submission

042553-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4956 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

4331325-4352978 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 4339530 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 280 (D280E)

Ref Sequence

ENSEMBL: ENSMUSP00000025078 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025078] [ENSMUST00000173930]

AlphaFold

Q07174

Predicted Effect

probably benign
Transcript: ENSMUST00000025078
AA Change: D280E

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000025078
Gene: ENSMUSG00000024235
AA Change: D280E

Domain	Start	End	E-Value	Type
Pfam:Pkinase	137	388	1.1e-47	PFAM
Pfam:Pkinase_Tyr	139	386	4.6e-26	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000105472

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000173708

Predicted Effect

probably benign
Transcript: ENSMUST00000173930

SMART Domains

Protein: ENSMUSP00000133469
Gene: ENSMUSG00000024235

Domain	Start	End	E-Value	Type
SCOP:d1phk__	146	169	2e-4	SMART

Meta Mutation Damage Score

0.1322

Coding Region Coverage

1x: 99.0%
3x: 98.2%
10x: 95.9%
20x: 91.1%

Validation Efficiency

96% (70/73)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
PHENOTYPE: Mutant mice resist endotoxic shock. Their MHC II expression is enhanced. Macrophages' TNF-alpha response to viruses and to all TLR ligands is impaired. Macrophage and T-cell secretion of other cytokines in response to various TLR ligands or OVA is aberrant. Anti-OVA Ig classes are abnormally skewed. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3110009E18Rik	G	C	1: 120,096,840 (GRCm39)		probably benign	Het
3110009E18Rik	C	T	1: 120,096,850 (GRCm39)		probably benign	Het
3110009E18Rik	G	T	1: 120,096,849 (GRCm39)		probably benign	Het
4930562C15Rik	A	G	16: 4,672,816 (GRCm39)	K866E	probably damaging	Het
Afap1l2	T	C	19: 56,931,879 (GRCm39)	M49V	probably benign	Het
Atf7ip	C	T	6: 136,583,808 (GRCm39)	R1280C	probably damaging	Het
Atp2a2	A	G	5: 122,599,643 (GRCm39)	F583L	probably benign	Het
Atxn7l3b	A	G	10: 112,764,501 (GRCm39)	C43R	probably damaging	Het
Axin2	T	C	11: 108,833,904 (GRCm39)	V617A	probably damaging	Het
Bltp3a	T	A	17: 28,108,958 (GRCm39)		probably null	Het
Brd1	A	T	15: 88,614,316 (GRCm39)	F193Y	probably damaging	Het
Cdc27	T	C	11: 104,420,221 (GRCm39)	S141G	probably damaging	Het
Chst9	A	T	18: 15,851,045 (GRCm39)	F7Y	probably damaging	Het
Cpn2	T	A	16: 30,079,233 (GRCm39)	Q156L	possibly damaging	Het
Dcaf6	A	T	1: 165,216,354 (GRCm39)	D416E	probably benign	Het
Dync1h1	C	A	12: 110,624,560 (GRCm39)	T3700N	probably damaging	Het
Eif2s3y	A	G	Y: 1,023,407 (GRCm39)	T430A	possibly damaging	Het
Enah	G	A	1: 181,745,854 (GRCm39)	T401I	probably damaging	Het
Esp38	T	G	17: 40,266,053 (GRCm39)	I54R	probably damaging	Het
Ffar4	C	T	19: 38,086,028 (GRCm39)	R152W	probably benign	Het
Flvcr1	A	G	1: 190,758,383 (GRCm39)		probably benign	Het
Fzd9	G	A	5: 135,278,796 (GRCm39)	A363V	probably damaging	Het
Gadl1	T	A	9: 115,869,987 (GRCm39)	I451N	probably benign	Het
Hmg20a	A	G	9: 56,388,948 (GRCm39)	T172A	probably damaging	Het
Ints1	G	A	5: 139,742,885 (GRCm39)	T1695M	probably damaging	Het
Ipo13	G	A	4: 117,758,768 (GRCm39)	A699V	probably benign	Het
Ipo9	A	G	1: 135,331,960 (GRCm39)		probably null	Het
Klra17	A	G	6: 129,850,279 (GRCm39)	L57P	probably damaging	Het
Mycbp2	A	G	14: 103,524,675 (GRCm39)	F662L	probably damaging	Het
Ncor1	T	A	11: 62,231,431 (GRCm39)	H792L	probably damaging	Het
Nlrx1	T	A	9: 44,173,909 (GRCm39)	K431*	probably null	Het
Nos1	A	G	5: 118,085,575 (GRCm39)	N1301S	probably benign	Het
Obp2b	A	G	2: 25,627,087 (GRCm39)	T7A	probably damaging	Het
Odc1	T	C	12: 17,597,958 (GRCm39)	I95T	probably damaging	Het
Or2t43	A	G	11: 58,457,344 (GRCm39)	Y276H	probably damaging	Het
Or4c127	G	A	2: 89,833,187 (GRCm39)	V146M	probably benign	Het
Or5b97	C	T	19: 12,878,963 (GRCm39)	M60I	probably damaging	Het
Or6ae1	A	G	7: 139,741,993 (GRCm39)	I290T	possibly damaging	Het
Or6c1	A	T	10: 129,517,968 (GRCm39)	F213L	probably benign	Het
Pcif1	A	T	2: 164,731,610 (GRCm39)	Q521L	probably damaging	Het
Plekhg2	A	C	7: 28,067,780 (GRCm39)	L223R	probably damaging	Het
Plod3	A	G	5: 137,018,772 (GRCm39)	N270D	probably damaging	Het
Ppp1r37	A	T	7: 19,266,636 (GRCm39)	L417*	probably null	Het
Psmd6	C	T	14: 14,116,166 (GRCm38)	V141I	probably benign	Het
Rcn1	A	T	2: 105,225,121 (GRCm39)	Y111*	probably null	Het
Rell2	G	A	18: 38,090,758 (GRCm39)	R145H	probably damaging	Het
Scaper	T	C	9: 55,745,426 (GRCm39)	K614R	probably damaging	Het
Scart2	A	G	7: 139,878,275 (GRCm39)	I1001V	probably benign	Het
Shbg	C	T	11: 69,508,045 (GRCm39)	E107K	probably damaging	Het
Slc30a3	G	A	5: 31,244,247 (GRCm39)	P345L	possibly damaging	Het
Tchp	A	C	5: 114,857,681 (GRCm39)	E391D	probably damaging	Het
Timeless	A	G	10: 128,077,520 (GRCm39)	D200G	probably damaging	Het
Tspear	A	G	10: 77,700,601 (GRCm39)	T144A	possibly damaging	Het
Usp5	C	G	6: 124,799,593 (GRCm39)	K318N	possibly damaging	Het
Vgll3	T	C	16: 65,624,820 (GRCm39)	V56A	possibly damaging	Het
Vmn2r71	C	T	7: 85,268,436 (GRCm39)	T213I	probably benign	Het
Wtap	T	C	17: 13,186,423 (GRCm39)	T375A	probably benign	Het
Yipf2	T	G	9: 21,503,204 (GRCm39)	T88P	probably damaging	Het
Zfp382	T	A	7: 29,830,979 (GRCm39)	D89E	probably benign	Het
Zfp955b	C	T	17: 33,524,209 (GRCm39)		probably benign	Het
Zpr1	C	T	9: 46,185,961 (GRCm39)	T144I	probably damaging	Het

Other mutations in Map3k8

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02458:Map3k8	APN	18	4,334,660 (GRCm39)	missense	probably damaging	1.00
IGL02483:Map3k8	APN	18	4,349,318 (GRCm39)	utr 5 prime	probably benign
IGL03174:Map3k8	APN	18	4,349,247 (GRCm39)	missense	probably damaging	1.00
Flojo	UTSW	18	4,339,548 (GRCm39)	missense	possibly damaging	0.95
gnostic_gospel	UTSW	18	4,333,965 (GRCm39)	missense	probably damaging	1.00
juicy	UTSW	18	4,339,552 (GRCm39)	missense	probably damaging	0.99
Sluggish	UTSW	18	4,339,608 (GRCm39)	splice site	probably benign
R0304:Map3k8	UTSW	18	4,339,552 (GRCm39)	missense	probably damaging	0.99
R0569:Map3k8	UTSW	18	4,349,162 (GRCm39)	missense	probably benign	0.00
R1748:Map3k8	UTSW	18	4,334,766 (GRCm39)	missense	probably damaging	1.00
R1793:Map3k8	UTSW	18	4,332,389 (GRCm39)	nonsense	probably null
R2310:Map3k8	UTSW	18	4,349,001 (GRCm39)	missense	probably benign
R3625:Map3k8	UTSW	18	4,333,965 (GRCm39)	missense	probably damaging	1.00
R4786:Map3k8	UTSW	18	4,340,647 (GRCm39)	nonsense	probably null
R4921:Map3k8	UTSW	18	4,349,124 (GRCm39)	missense	possibly damaging	0.92
R4930:Map3k8	UTSW	18	4,349,215 (GRCm39)	nonsense	probably null
R4934:Map3k8	UTSW	18	4,339,548 (GRCm39)	missense	possibly damaging	0.95
R5241:Map3k8	UTSW	18	4,340,750 (GRCm39)	missense	probably damaging	0.98
R5549:Map3k8	UTSW	18	4,340,762 (GRCm39)	missense	probably damaging	0.98
R6317:Map3k8	UTSW	18	4,348,979 (GRCm39)	critical splice donor site	probably null
R6326:Map3k8	UTSW	18	4,340,651 (GRCm39)	missense	probably damaging	1.00
R6910:Map3k8	UTSW	18	4,340,801 (GRCm39)	missense	probably benign	0.03
R7010:Map3k8	UTSW	18	4,334,060 (GRCm39)	missense	probably damaging	1.00
R7247:Map3k8	UTSW	18	4,334,036 (GRCm39)	missense	probably damaging	1.00
R7300:Map3k8	UTSW	18	4,349,076 (GRCm39)	missense	probably damaging	0.98
R7348:Map3k8	UTSW	18	4,340,561 (GRCm39)	missense	probably damaging	1.00
R7903:Map3k8	UTSW	18	4,349,162 (GRCm39)	missense	probably benign	0.00
R8302:Map3k8	UTSW	18	4,334,064 (GRCm39)	missense	probably damaging	0.97
R8676:Map3k8	UTSW	18	4,343,137 (GRCm39)	missense	probably benign	0.01
R8847:Map3k8	UTSW	18	4,333,889 (GRCm39)	missense
R9068:Map3k8	UTSW	18	4,340,557 (GRCm39)	missense	probably benign	0.36
R9352:Map3k8	UTSW	18	4,349,170 (GRCm39)	missense	probably benign
R9460:Map3k8	UTSW	18	4,349,277 (GRCm39)	missense	probably benign	0.00
R9526:Map3k8	UTSW	18	4,333,869 (GRCm39)	missense	probably damaging	1.00
R9548:Map3k8	UTSW	18	4,349,141 (GRCm39)	missense	probably benign
R9632:Map3k8	UTSW	18	4,339,546 (GRCm39)	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- GGCACTGAATTGTCTGTAAGTGC -3'
(R):5'- AGAAGCGTTTCCTTCTGCTCTG -3'

Sequencing Primer
(F):5'- ACTGAATTGTCTGTAAGTGCTTTGTG -3'
(R):5'- TGCTCTGCTTGGAACTTGC -3'

Posted On

2016-04-27