Mutagenetix > Incidental Mutation

Incidental Mutation 'R6326:Map3k8'

510451

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

044480-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R6326 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

4331325-4352978 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 4340651 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Asparagine at position 221 (S221N)

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: S221N

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000025078
Gene: ENSMUSG00000024235
AA Change: S221N

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

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: 99.5%
20x: 98.3%

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamts17	A	T	7: 66,770,636 (GRCm39)	Y915F	probably benign	Het
Adap2	T	A	11: 80,045,848 (GRCm39)	F43I	probably damaging	Het
Adprs	A	T	4: 126,210,406 (GRCm39)	L358Q	possibly damaging	Het
Akap9	A	C	5: 4,012,061 (GRCm39)	Q921H	probably damaging	Het
Amigo2	A	G	15: 97,143,256 (GRCm39)	S389P	probably benign	Het
Atg2b	A	T	12: 105,627,351 (GRCm39)	C545*	probably null	Het
C2cd3	A	G	7: 100,065,635 (GRCm39)	E807G	probably benign	Het
Ccdc110	A	G	8: 46,395,078 (GRCm39)	E323G	probably damaging	Het
Cdk5rap2	T	A	4: 70,153,691 (GRCm39)	S1711C	probably damaging	Het
Cebpzos	T	G	17: 79,226,486 (GRCm39)	D39E	probably damaging	Het
Cenpe	A	G	3: 134,945,539 (GRCm39)	N1018D	probably benign	Het
Cfap68	T	G	9: 50,676,057 (GRCm39)	N87T	probably damaging	Het
Clspn	C	A	4: 126,459,532 (GRCm39)	H141Q	probably damaging	Het
Cluh	C	T	11: 74,557,068 (GRCm39)	A1010V	probably benign	Het
Col27a1	G	T	4: 63,242,678 (GRCm39)		probably benign	Het
Cpt2	T	C	4: 107,771,513 (GRCm39)	M61V	probably benign	Het
Ddr2	T	A	1: 169,814,709 (GRCm39)	H578L	probably damaging	Het
Dnah14	T	A	1: 181,611,121 (GRCm39)	I3749N	probably damaging	Het
Dnajc18	T	C	18: 35,813,978 (GRCm39)	T264A	possibly damaging	Het
Ecpas	T	A	4: 58,827,068 (GRCm39)	T1022S	probably benign	Het
Eml6	T	C	11: 29,769,066 (GRCm39)	N693S	probably damaging	Het
Ephx4	A	G	5: 107,553,977 (GRCm39)	E9G	probably damaging	Het
Eps15l1	G	A	8: 73,095,278 (GRCm39)	Q747*	probably null	Het
Flrt1	C	T	19: 7,073,974 (GRCm39)	S191N	probably damaging	Het
Gm5114	C	T	7: 39,057,579 (GRCm39)	R680H	probably benign	Het
Gm5431	T	C	11: 48,780,172 (GRCm39)	H250R	probably damaging	Het
Gm7233	T	C	14: 43,040,342 (GRCm39)	C198R	possibly damaging	Het
Herc2	C	G	7: 55,872,682 (GRCm39)	Q4407E	probably damaging	Het
Hmx3	C	G	7: 131,144,734 (GRCm39)		probably benign	Het
Hoxb7	C	A	11: 96,177,909 (GRCm39)	A119E	probably benign	Het
Ifi207	A	T	1: 173,557,532 (GRCm39)	M402K	probably benign	Het
Ints14	T	C	9: 64,871,719 (GRCm39)	V19A	probably benign	Het
Itgae	T	A	11: 73,022,519 (GRCm39)	N911K	possibly damaging	Het
Kif1a	T	C	1: 93,004,048 (GRCm39)	S145G	probably damaging	Het
Klhdc4	A	G	8: 122,531,793 (GRCm39)	W187R	probably damaging	Het
Krt1	A	T	15: 101,758,684 (GRCm39)	I160N	probably damaging	Het
Krt12	T	C	11: 99,307,745 (GRCm39)	T448A	probably benign	Het
Lcmt2	G	A	2: 120,969,938 (GRCm39)	R382*	probably null	Het
Med17	T	C	9: 15,190,854 (GRCm39)	D79G	probably benign	Het
Mlf1	A	T	3: 67,307,060 (GRCm39)	I257F	probably damaging	Het
Mov10l1	T	A	15: 88,879,098 (GRCm39)	F153I	probably damaging	Het
Msto1	A	C	3: 88,819,405 (GRCm39)	V149G	probably damaging	Het
Mybl1	T	C	1: 9,748,732 (GRCm39)		probably null	Het
Myoc	A	G	1: 162,476,580 (GRCm39)	Y428C	probably damaging	Het
Nin	A	G	12: 70,091,955 (GRCm39)	S785P	possibly damaging	Het
Oit3	A	T	10: 59,264,061 (GRCm39)	F358I	probably damaging	Het
Or5t15	C	T	2: 86,681,338 (GRCm39)	V235I	probably benign	Het
Or6c88	A	G	10: 129,406,571 (GRCm39)	T16A	possibly damaging	Het
Paip1	A	G	13: 119,566,753 (GRCm39)	N29S	probably benign	Het
Pcdhgb4	T	C	18: 37,855,509 (GRCm39)	S635P	probably benign	Het
Pcsk1	A	G	13: 75,280,298 (GRCm39)	N708D	possibly damaging	Het
Plch1	C	T	3: 63,688,811 (GRCm39)	W131*	probably null	Het
Prag1	A	T	8: 36,569,860 (GRCm39)	M148L	possibly damaging	Het
Ptch1	A	G	13: 63,691,359 (GRCm39)	L176P	probably damaging	Het
Ralgapa1	A	T	12: 55,793,931 (GRCm39)	V568D	probably damaging	Het
Rb1	A	T	14: 73,435,974 (GRCm39)	M897K	probably benign	Het
Resf1	T	A	6: 149,230,493 (GRCm39)	Y1180N	probably damaging	Het
Robo3	T	A	9: 37,338,323 (GRCm39)	Q386L	probably damaging	Het
Rtn4rl1	T	C	11: 75,156,828 (GRCm39)	V420A	possibly damaging	Het
Sall1	A	T	8: 89,756,896 (GRCm39)	N1069K	probably benign	Het
Sipa1l1	A	G	12: 82,419,242 (GRCm39)	E640G	probably damaging	Het
Slc22a2	C	A	17: 12,831,297 (GRCm39)	Y362*	probably null	Het
Slc5a9	T	C	4: 111,737,450 (GRCm39)	E603G	probably benign	Het
Slc6a17	A	T	3: 107,407,722 (GRCm39)	I83N	probably damaging	Het
Snx29	G	T	16: 11,221,430 (GRCm39)	M285I	probably benign	Het
Spata2	T	C	2: 167,326,094 (GRCm39)	T242A	possibly damaging	Het
Stard13	A	G	5: 150,970,384 (GRCm39)	L733P	possibly damaging	Het
Svep1	A	G	4: 58,073,045 (GRCm39)	V2088A	possibly damaging	Het
Tdp2	A	G	13: 25,024,540 (GRCm39)	E279G	probably damaging	Het
Tnfrsf8	T	G	4: 144,995,794 (GRCm39)	I422L	probably damaging	Het
Tpk1	T	A	6: 43,323,736 (GRCm39)	T189S	possibly damaging	Het
Trhde	A	T	10: 114,403,129 (GRCm39)	M498K	probably damaging	Het
Trim35	T	A	14: 66,540,653 (GRCm39)	H168Q	possibly damaging	Het
Tubb5	T	C	17: 36,147,347 (GRCm39)		probably benign	Het
Tut4	C	T	4: 108,336,177 (GRCm39)	T6I	probably benign	Het
Vmn1r181	G	A	7: 23,684,183 (GRCm39)	R216Q	probably benign	Het
Vmn2r77	G	A	7: 86,451,031 (GRCm39)	G306R	probably benign	Het
Xkr4	C	T	1: 3,741,261 (GRCm39)	R104H	possibly damaging	Het
Zfp398	T	C	6: 47,843,355 (GRCm39)	I337T	possibly 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
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
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'- AAGGATGCTGTGTCTGCAGG -3'
(R):5'- CACCACGGTGCTCTGTTATAC -3'

Sequencing Primer
(F):5'- CTGTGTCTGCAGGGAGCTG -3'
(R):5'- CGGTGCTCTGTTATACACATCAAGG -3'

Posted On

2018-04-02