Mutagenetix > Incidental Mutation

Incidental Mutation 'R9632:Map3k8'

725635

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

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R9632 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

4331325-4352978 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 4339546 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Aspartic acid at position 275 (V275D)

Ref Sequence

ENSEMBL: ENSMUSP00000025078 (fasta)

Gene Model

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

AlphaFold

Q07174

Predicted Effect

probably damaging
Transcript: ENSMUST00000025078
AA Change: V275D

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000025078
Gene: ENSMUSG00000024235
AA Change: V275D

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

probably benign
Transcript: ENSMUST00000173930

SMART Domains

Protein: ENSMUSP00000133469
Gene: ENSMUSG00000024235

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.1%

Validation Efficiency

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: 98 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acly	A	G	11: 100,389,072 (GRCm39)	I570T	probably damaging	Het
Adamtsl4	G	A	3: 95,589,090 (GRCm39)	T447I	probably damaging	Het
Ahcyl1	T	A	3: 107,578,494 (GRCm39)	I248F	possibly damaging	Het
Arhgef2	T	C	3: 88,528,576 (GRCm39)	I4T	probably benign	Het
Bin2	T	C	15: 100,549,915 (GRCm39)	D176G	possibly damaging	Het
Bptf	T	A	11: 106,952,545 (GRCm39)	T2166S	probably damaging	Het
Cachd1	T	A	4: 100,832,092 (GRCm39)	N751K	probably benign	Het
Castor1	A	G	11: 4,169,015 (GRCm39)	K61E	probably benign	Het
CN725425	A	T	15: 91,126,851 (GRCm39)	T214S	possibly damaging	Het
Crtam	A	T	9: 40,895,671 (GRCm39)	D218E	probably benign	Het
Ctsj	C	T	13: 61,151,828 (GRCm39)	M76I	probably benign	Het
Cuedc1	C	A	11: 88,060,955 (GRCm39)	S99R	possibly damaging	Het
Cyp4a14	T	A	4: 115,349,347 (GRCm39)	I238F	probably benign	Het
Dnajb11	A	T	16: 22,681,344 (GRCm39)	I41F	probably damaging	Het
Drd3	A	G	16: 43,643,135 (GRCm39)	N425S	probably damaging	Het
Eci1	G	C	17: 24,645,859 (GRCm39)	G25R	probably damaging	Het
Etl4	A	T	2: 20,666,749 (GRCm39)	N52I	probably benign	Het
Fbxo34	T	C	14: 47,768,724 (GRCm39)	Y746H	probably damaging	Het
Fcgbpl1	A	G	7: 27,841,726 (GRCm39)	I554V	probably benign	Het
Fndc1	T	C	17: 7,991,622 (GRCm39)	I691M	unknown	Het
Fut8	A	G	12: 77,440,507 (GRCm39)	T165A	probably benign	Het
Galr1	A	T	18: 82,424,103 (GRCm39)	L58Q	probably damaging	Het
Glt28d2	T	C	3: 85,779,059 (GRCm39)	D138G	probably benign	Het
Gm11595	A	T	11: 99,663,097 (GRCm39)	C194*	probably null	Het
Gm14403	T	A	2: 177,201,421 (GRCm39)	N213K	probably benign	Het
Gmpr	T	C	13: 45,699,519 (GRCm39)	V343A	probably benign	Het
Hacd1	T	C	2: 14,040,678 (GRCm39)	N152D	possibly damaging	Het
Hcn1	A	G	13: 118,010,522 (GRCm39)	S367G	probably benign	Het
Impg1	A	G	9: 80,287,276 (GRCm39)	V390A	probably benign	Het
Itpr1	T	C	6: 108,382,481 (GRCm39)	C1458R	possibly damaging	Het
Kif16b	A	T	2: 142,553,960 (GRCm39)	V946E	probably benign	Het
Krt71	T	C	15: 101,644,988 (GRCm39)	E441G	probably damaging	Het
Lhcgr	A	G	17: 89,049,532 (GRCm39)	F665L	probably benign	Het
Lrrc37	T	A	11: 103,433,252 (GRCm39)	S3306C	unknown	Het
Lzic	T	A	4: 149,573,141 (GRCm39)	F98I	probably damaging	Het
Marchf8	C	T	6: 116,378,405 (GRCm39)	T113I	possibly damaging	Het
Mmp15	A	G	8: 96,098,731 (GRCm39)		probably null	Het
Mpst	A	G	15: 78,294,469 (GRCm39)	D67G	probably damaging	Het
Nanog	T	C	6: 122,684,799 (GRCm39)	S20P	probably benign	Het
Ndufc2	T	C	7: 97,056,102 (GRCm39)	S67P	probably damaging	Het
Nrg1	T	C	8: 32,407,621 (GRCm39)	K204R	possibly damaging	Het
Nsf	T	A	11: 103,714,594 (GRCm39)	K728N	probably damaging	Het
Nutm2	C	A	13: 50,628,901 (GRCm39)	P655H	probably benign	Het
Obscn	G	A	11: 58,943,397 (GRCm39)	R4251C	probably benign	Het
Or10g9	A	T	9: 39,912,172 (GRCm39)	M117K	probably damaging	Het
Or11h4	C	T	14: 50,974,199 (GRCm39)	C140Y	probably benign	Het
Or4a15	T	C	2: 89,193,065 (GRCm39)	Y236C	probably damaging	Het
Or4c102	A	T	2: 88,423,057 (GRCm39)	Q303L	probably benign	Het
Or4c120	T	C	2: 89,001,752 (GRCm39)		probably benign	Het
Or56a5	T	A	7: 104,793,165 (GRCm39)	T112S	probably benign	Het
Otog	A	T	7: 45,915,143 (GRCm39)	Q836L	probably benign	Het
Pcdhb11	T	C	18: 37,556,019 (GRCm39)	F450L	probably damaging	Het
Pelp1	T	C	11: 70,284,835 (GRCm39)	E1011G	unknown	Het
Pfkfb3	T	G	2: 11,486,109 (GRCm39)	R459S	probably benign	Het
Pgm1	T	C	4: 99,843,918 (GRCm39)	L567P	probably damaging	Het
Phf2	T	A	13: 48,971,292 (GRCm39)	D460V	unknown	Het
Polr1f	G	A	12: 33,479,723 (GRCm39)	G24R	possibly damaging	Het
Pou5f1	G	A	17: 35,819,731 (GRCm39)		probably benign	Het
Pou6f2	T	C	13: 18,299,848 (GRCm39)	R604G		Het
Pramel5	T	A	4: 143,999,545 (GRCm39)	I181F	probably benign	Het
Ptprc	T	C	1: 138,008,627 (GRCm39)	R687G	probably damaging	Het
Ptprz1	T	A	6: 23,007,292 (GRCm39)	H1618Q	probably damaging	Het
Qars1	G	A	9: 108,391,582 (GRCm39)	D618N	probably damaging	Het
Ripply3	A	G	16: 94,134,139 (GRCm39)	T68A	probably benign	Het
Rrad	A	G	8: 105,356,320 (GRCm39)	M160T	probably benign	Het
Rtn1	A	G	12: 72,350,961 (GRCm39)	V416A	probably damaging	Het
Rttn	A	G	18: 89,035,334 (GRCm39)	N736S	possibly damaging	Het
Sash1	A	T	10: 8,615,969 (GRCm39)	V631E	probably damaging	Het
Selenof	T	A	3: 144,283,370 (GRCm39)	F33L	probably benign	Het
Serpinb6b	A	T	13: 33,155,532 (GRCm39)	N82Y	possibly damaging	Het
Sez6	G	A	11: 77,865,121 (GRCm39)	E623K	possibly damaging	Het
Shpk	G	T	11: 73,104,238 (GRCm39)	R129L	probably damaging	Het
Slc2a10	A	C	2: 165,358,176 (GRCm39)	I434L	probably damaging	Het
Slc30a6	G	T	17: 74,730,059 (GRCm39)	M316I	probably benign	Het
Slx4	A	T	16: 3,803,969 (GRCm39)	H948Q	probably benign	Het
Sncaip	A	G	18: 53,039,726 (GRCm39)	E640G	probably damaging	Het
Sox7	G	A	14: 64,185,509 (GRCm39)	A182T	probably benign	Het
Spata31e5	T	A	1: 28,817,120 (GRCm39)	Y304F	probably benign	Het
Srcin1	A	G	11: 97,442,648 (GRCm39)	I60T	probably benign	Het
Srm	C	T	4: 148,676,039 (GRCm39)		probably benign	Het
Srrt	A	T	5: 137,296,689 (GRCm39)	M447K	possibly damaging	Het
Stam	A	T	2: 14,122,204 (GRCm39)	H101L	probably damaging	Het
Suz12	C	T	11: 79,915,748 (GRCm39)	T407M	possibly damaging	Het
Tbc1d10b	A	G	7: 126,807,036 (GRCm39)	V167A	probably benign	Het
Trav16	T	A	14: 53,980,910 (GRCm39)	V33E	possibly damaging	Het
Tshr	C	T	12: 91,504,409 (GRCm39)	P449L	probably damaging	Het
Ttc17	A	G	2: 94,209,097 (GRCm39)	V119A	probably damaging	Het
Ttc19	A	G	11: 62,203,997 (GRCm39)	I319M	probably benign	Het
Ttc6	A	G	12: 57,664,299 (GRCm39)	M351V	probably benign	Het
Ttn	G	A	2: 76,714,897 (GRCm39)	R8026*	probably null	Het
Ttn	A	T	2: 76,750,210 (GRCm39)	V3613E	probably benign	Het
Txndc16	T	C	14: 45,400,467 (GRCm39)	I345V	probably benign	Het
Ube3b	T	C	5: 114,553,370 (GRCm39)	I914T	probably benign	Het
Vmn1r73	T	C	7: 11,490,407 (GRCm39)	F75S	possibly damaging	Het
Vmn2r54	A	T	7: 12,363,753 (GRCm39)	M380K	possibly damaging	Het
Zfp820	T	C	17: 22,038,107 (GRCm39)	Y407C	probably damaging	Het
Zic5	C	T	14: 122,701,787 (GRCm39)	A315T	unknown	Het
Zmiz1	C	A	14: 25,663,411 (GRCm39)	D1053E	unknown	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
R4956:Map3k8	UTSW	18	4,339,530 (GRCm39)	missense	probably benign	0.00
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

Predicted Primers

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

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

Posted On

2022-09-12