Mutagenetix > Incidental Mutation

Incidental Mutation 'R7903:Map3k8'

610122

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

045955-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7903 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

4331325-4352978 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 4349162 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 52 (D52G)

Ref Sequence

ENSEMBL: ENSMUSP00000133469 (fasta)

Gene Model

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

AlphaFold

Q07174

Predicted Effect

probably benign
Transcript: ENSMUST00000025078
AA Change: D52G

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000025078
Gene: ENSMUSG00000024235
AA Change: D52G

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: ENSMUST00000172805

Predicted Effect

probably benign
Transcript: ENSMUST00000173930
AA Change: D52G

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

SMART Domains

Protein: ENSMUSP00000133469
Gene: ENSMUSG00000024235
AA Change: D52G

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

Meta Mutation Damage Score

0.1105

Coding Region Coverage

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

Validation Efficiency

100% (67/67)

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: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700062C07Rik	T	C	18: 24,608,783 (GRCm39)		probably null	Het
Acsm2	A	T	7: 119,195,215 (GRCm39)	T596S	probably benign	Het
Aggf1	T	C	13: 95,492,966 (GRCm39)	K548E	probably damaging	Het
Anapc15	T	G	7: 101,547,193 (GRCm39)	V23G	probably benign	Het
Atp10a	T	C	7: 58,308,570 (GRCm39)	L123P	probably damaging	Het
Brf2	G	A	8: 27,616,121 (GRCm39)	T88M	possibly damaging	Het
C1ra	G	A	6: 124,494,684 (GRCm39)	E316K	probably benign	Het
Ccdc14	A	T	16: 34,525,280 (GRCm39)	H191L	probably damaging	Het
Cdc42bpg	T	A	19: 6,363,499 (GRCm39)	V453E	possibly damaging	Het
Corin	T	C	5: 72,458,843 (GRCm39)	K1110E	probably benign	Het
Cubn	T	C	2: 13,473,680 (GRCm39)	D421G	probably damaging	Het
D130043K22Rik	T	G	13: 25,059,995 (GRCm39)	V622G	probably damaging	Het
Ddb1	T	C	19: 10,585,712 (GRCm39)	V142A	probably benign	Het
Dnah3	A	G	7: 119,641,351 (GRCm39)	S1190P	probably damaging	Het
Eif4a3l2	A	G	6: 116,528,212 (GRCm39)	T30A	probably benign	Het
Elavl1	T	C	8: 4,351,756 (GRCm39)	K120R	probably benign	Het
Epb41l3	T	A	17: 69,581,332 (GRCm39)		probably null	Het
Fubp1	G	A	3: 151,920,498 (GRCm39)	W79*	probably null	Het
Gsto2	T	A	19: 47,873,096 (GRCm39)	I157N	possibly damaging	Het
Gucy2d	A	G	7: 98,108,272 (GRCm39)	D735G	probably damaging	Het
H2-D1	A	T	17: 35,482,967 (GRCm39)	I166F	probably damaging	Het
Hars2	C	A	18: 36,919,245 (GRCm39)	R128S	probably damaging	Het
Igf1r	T	C	7: 67,834,500 (GRCm39)	F496S	probably damaging	Het
Inf2	T	C	12: 112,578,988 (GRCm39)	V1256A	unknown	Het
Kif19b	T	C	5: 140,461,767 (GRCm39)	V523A	probably damaging	Het
Krt34	A	T	11: 99,932,321 (GRCm39)	M1K	probably null	Het
Lamtor2	T	C	3: 88,459,817 (GRCm39)	N26D	possibly damaging	Het
Map3k10	T	C	7: 27,357,382 (GRCm39)	T799A	probably damaging	Het
Mcm10	T	C	2: 5,000,613 (GRCm39)	T693A	probably benign	Het
Mgarp	G	T	3: 51,304,119 (GRCm39)	A10E		Het
Mns1	A	T	9: 72,360,093 (GRCm39)	E414D	probably benign	Het
Myo16	A	G	8: 10,426,265 (GRCm39)	S341G	probably null	Het
Nags	A	T	11: 102,037,503 (GRCm39)	D198V	possibly damaging	Het
Nedd4l	C	T	18: 65,319,438 (GRCm39)	P464S	probably damaging	Het
Nicol1	T	A	5: 34,140,910 (GRCm39)		probably null	Het
Nsfl1c	T	C	2: 151,338,522 (GRCm39)	Y42H	probably damaging	Het
Obscn	T	C	11: 58,969,942 (GRCm39)	M67V	probably benign	Het
Or2b28	T	A	13: 21,532,046 (GRCm39)	I316K	probably benign	Het
Pcsk5	A	T	19: 17,549,847 (GRCm39)	L715Q	probably damaging	Het
Peg3	GTGGGGCTCCTGGCCATGGGGCTTATCATCATGGGGCTCCTGGCCATGGGGCTTATCATCATGGGGCTCCTGGCCATGGGGCTTATCATCATGGGGCTC	GTGGGGCTCCTGGCCATGGGGCTTATCATCATGGGGCTCCTGGCCATGGGGCTTATCATCATGGGGCTC	7: 6,712,167 (GRCm39)		probably benign	Het
Pfkfb4	A	T	9: 108,828,019 (GRCm39)	N64Y	probably damaging	Het
Pidd1	A	G	7: 141,019,744 (GRCm39)	F673L	probably damaging	Het
Pla2g7	A	G	17: 43,911,512 (GRCm39)		probably null	Het
Pml	T	C	9: 58,156,867 (GRCm39)	E36G	probably benign	Het
Proser1	C	A	3: 53,386,503 (GRCm39)	S795*	probably null	Het
Ptprs	T	A	17: 56,731,960 (GRCm39)	K1016*	probably null	Het
Rbfox1	T	A	16: 7,042,375 (GRCm39)	S76R	probably benign	Het
Reck	A	T	4: 43,927,166 (GRCm39)	I486F	possibly damaging	Het
Rnf103	A	T	6: 71,486,138 (GRCm39)	K256N	probably damaging	Het
Setd2	A	T	9: 110,446,905 (GRCm39)	N713I		Het
Slc38a4	C	T	15: 96,906,809 (GRCm39)	G310S	probably benign	Het
Slc7a4	C	T	16: 17,393,145 (GRCm39)	R218H	probably benign	Het
Slc7a7	T	C	14: 54,611,366 (GRCm39)	H344R	probably damaging	Het
Smarcc1	G	A	9: 110,033,334 (GRCm39)	E810K	probably benign	Het
Sord	T	A	2: 122,093,706 (GRCm39)	M275K	probably benign	Het
Spire2	C	A	8: 124,095,489 (GRCm39)	P631T	probably benign	Het
Sult6b1	T	C	17: 79,198,279 (GRCm39)	K207R	probably benign	Het
Syde2	T	A	3: 145,704,543 (GRCm39)	D498E	probably damaging	Het
Syne2	C	T	12: 76,110,958 (GRCm39)	T1024M	probably damaging	Het
Tdrd9	T	A	12: 112,018,410 (GRCm39)	D1276E	possibly damaging	Het
Tm7sf2	A	G	19: 6,121,365 (GRCm39)	F219S	probably damaging	Het
Tmcc2	C	T	1: 132,288,199 (GRCm39)	G496D	probably benign	Het
Tmtc4	G	A	14: 123,165,060 (GRCm39)	H600Y	probably benign	Het
Vmn1r224	A	T	17: 20,640,309 (GRCm39)	L295F	probably benign	Het
Vmn1r91	T	C	7: 19,835,135 (GRCm39)	I18T	possibly damaging	Het
Vwa7	G	A	17: 35,236,763 (GRCm39)	R110H	probably damaging	Het
Wbp2nl	C	T	15: 82,190,332 (GRCm39)	Q87*	probably null	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
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'- CCACTGTGCATTCAATGAAGC -3'
(R):5'- CTTCTGTAGACTCCCAGCAG -3'

Sequencing Primer
(F):5'- TGTGCATTCAATGAAGCACTACCAG -3'
(R):5'- GTAGACTCCCAGCAGGCACTAC -3'

Posted On

2019-12-20