Mutagenetix > Incidental Mutation

Incidental Mutation 'R4523:Map3k3'

334319

Institutional Source

Beutler Lab

Gene Symbol

Map3k3

Ensembl Gene

ENSMUSG00000020700

Gene Name

mitogen-activated protein kinase kinase kinase 3

Synonyms

MAPKKK3, Mekk3

MMRRC Submission

042004-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4523 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

105975439-106046272 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 106039694 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Histidine at position 278 (R278H)

Ref Sequence

ENSEMBL: ENSMUSP00000002044 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000002044]

AlphaFold

Q61084

Predicted Effect

probably damaging
Transcript: ENSMUST00000002044
AA Change: R278H

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000002044
Gene: ENSMUSG00000020700
AA Change: R278H

Domain	Start	End	E-Value	Type
PB1	44	123	1.04e-18	SMART
S_TKc	362	622	4.23e-95	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124449

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129793

Meta Mutation Damage Score

0.3782

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.2%

Validation Efficiency

100% (61/61)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die as embryos before E11.5. vascular remodeling does not take place normally. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 54 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Atp8a1	G	T	5: 67,824,943 (GRCm39)	T796K	probably benign	Het
Atr	T	C	9: 95,744,916 (GRCm39)	S78P	probably damaging	Het
Calb2	C	T	8: 110,875,141 (GRCm39)		probably null	Het
Ccdc88c	G	T	12: 100,879,591 (GRCm39)	S1843R	possibly damaging	Het
Cdca7	A	G	2: 72,310,042 (GRCm39)	S77G	probably damaging	Het
Cfap47	A	T	X: 78,553,601 (GRCm39)	N291K	possibly damaging	Het
Cnot2	C	T	10: 116,417,379 (GRCm39)		probably benign	Het
Cstf2t	T	A	19: 31,060,482 (GRCm39)	V6D	possibly damaging	Het
Cybc1	A	G	11: 121,114,934 (GRCm39)		probably benign	Het
Dido1	T	C	2: 180,314,085 (GRCm39)	I852V	probably damaging	Het
Dmgdh	C	T	13: 93,825,138 (GRCm39)	Q154*	probably null	Het
Dnah12	T	C	14: 26,491,979 (GRCm39)	F1138S	probably damaging	Het
Dnah12	G	A	14: 26,598,915 (GRCm39)	A998T	possibly damaging	Het
Dusp5	T	G	19: 53,526,032 (GRCm39)	Y225D	probably damaging	Het
Fam193a	G	A	5: 34,600,715 (GRCm39)	D601N	probably benign	Het
Fbxo41	A	G	6: 85,461,024 (GRCm39)	I228T	probably damaging	Het
Fmo2	T	C	1: 162,715,277 (GRCm39)	K115R	probably benign	Het
Gak	G	T	5: 108,724,432 (GRCm39)	Q1093K	probably benign	Het
Gm5277	G	T	3: 78,799,493 (GRCm39)		noncoding transcript	Het
Hgsnat	A	G	8: 26,458,389 (GRCm39)		probably null	Het
Hycc1	T	C	5: 24,170,120 (GRCm39)	T410A	probably benign	Het
Irag1	T	C	7: 110,523,048 (GRCm39)	M338V	probably benign	Het
Muc4	T	C	16: 32,555,154 (GRCm39)		probably benign	Het
Nectin3	C	A	16: 46,268,953 (GRCm39)	R483L	probably benign	Het
Nop2	G	T	6: 125,110,515 (GRCm39)	R47L	probably damaging	Het
Ntng1	A	G	3: 109,842,312 (GRCm39)	S154P	probably damaging	Het
Olfml2b	T	C	1: 170,496,791 (GRCm39)	I474T	probably benign	Het
Optc	G	T	1: 133,831,492 (GRCm39)	T138K	possibly damaging	Het
Or7g25	T	C	9: 19,160,525 (GRCm39)	T57A	probably damaging	Het
Or8k22	C	G	2: 86,163,644 (GRCm39)	D19H	probably benign	Het
Orc4	G	A	2: 48,827,501 (GRCm39)	P31S	probably benign	Het
Pabir3	G	A	X: 52,382,376 (GRCm39)	R94H	possibly damaging	Het
Pard3	C	T	8: 128,125,108 (GRCm39)	P421S	probably benign	Het
Pcdhb22	G	T	18: 37,653,474 (GRCm39)	E647D	probably benign	Het
Pclo	A	G	5: 14,730,006 (GRCm39)		probably benign	Het
Prkce	G	T	17: 86,798,178 (GRCm39)		probably null	Het
Prr12	T	C	7: 44,697,947 (GRCm39)	D656G	unknown	Het
Ptprk	A	T	10: 28,342,048 (GRCm39)	D485V	probably damaging	Het
Ptprn2	T	C	12: 116,839,620 (GRCm39)	L381P	probably damaging	Het
Rnf144b	T	C	13: 47,361,013 (GRCm39)	I51T	probably benign	Het
Rpl10l	T	C	12: 66,330,512 (GRCm39)	D207G	probably benign	Het
Sh3glb2	A	T	2: 30,240,711 (GRCm39)	V118E	probably damaging	Het
Sipa1l2	C	T	8: 126,219,163 (GRCm39)	G58D	probably damaging	Het
Slc5a4a	C	T	10: 75,984,196 (GRCm39)	A46V	probably damaging	Het
Spmip8	T	A	8: 96,039,638 (GRCm39)	Y18*	probably null	Het
Tgm7	C	A	2: 120,929,069 (GRCm39)		probably null	Het
Tjap1	A	G	17: 46,569,718 (GRCm39)	V424A	probably benign	Het
Trpm6	A	T	19: 18,773,864 (GRCm39)	I414F	probably damaging	Het
Tsr3	C	G	17: 25,460,723 (GRCm39)	D196E	probably benign	Het
Ubqlnl	C	T	7: 103,798,925 (GRCm39)	V191M	probably benign	Het
Vmn2r72	T	A	7: 85,401,134 (GRCm39)	H95L	probably benign	Het
Vmn2r97	T	A	17: 19,149,333 (GRCm39)	N240K	probably benign	Het
Xdh	C	A	17: 74,205,339 (GRCm39)	G1042V	probably damaging	Het
Zcchc4	A	G	5: 52,941,409 (GRCm39)	D68G	probably damaging	Het

Other mutations in Map3k3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01368:Map3k3	APN	11	106,041,215 (GRCm39)	missense	probably benign	0.01
IGL03028:Map3k3	APN	11	106,001,577 (GRCm39)	missense	probably damaging	1.00
BB003:Map3k3	UTSW	11	106,036,548 (GRCm39)	missense	probably damaging	1.00
BB013:Map3k3	UTSW	11	106,036,548 (GRCm39)	missense	probably damaging	1.00
R0421:Map3k3	UTSW	11	106,039,741 (GRCm39)	splice site	probably benign
R0963:Map3k3	UTSW	11	106,014,618 (GRCm39)	missense	probably benign	0.01
R3547:Map3k3	UTSW	11	106,033,379 (GRCm39)	nonsense	probably null
R5627:Map3k3	UTSW	11	106,039,428 (GRCm39)	missense	probably benign	0.03
R5747:Map3k3	UTSW	11	106,041,236 (GRCm39)	missense	probably benign	0.03
R5925:Map3k3	UTSW	11	106,040,376 (GRCm39)	missense	probably benign	0.07
R6141:Map3k3	UTSW	11	105,987,874 (GRCm39)	missense	probably benign	0.27
R6394:Map3k3	UTSW	11	106,039,709 (GRCm39)	missense	probably benign
R6714:Map3k3	UTSW	11	106,005,048 (GRCm39)	missense	possibly damaging	0.52
R7926:Map3k3	UTSW	11	106,036,548 (GRCm39)	missense	probably damaging	1.00
R9372:Map3k3	UTSW	11	106,033,335 (GRCm39)	missense	probably damaging	1.00
R9563:Map3k3	UTSW	11	106,041,860 (GRCm39)	missense	probably damaging	1.00
R9564:Map3k3	UTSW	11	106,041,860 (GRCm39)	missense	probably damaging	1.00
R9565:Map3k3	UTSW	11	106,041,860 (GRCm39)	missense	probably damaging	1.00
R9722:Map3k3	UTSW	11	106,033,361 (GRCm39)	missense	possibly damaging	0.66
Z1088:Map3k3	UTSW	11	106,041,179 (GRCm39)	missense	possibly damaging	0.91

Predicted Primers

PCR Primer
(F):5'- AGAATCTAGGTGGGCACTGC -3'
(R):5'- GCACAATGCCTCAGGAATAAG -3'

Sequencing Primer
(F):5'- TGGAGCCATAGATGCCTCTAAATTGG -3'
(R):5'- CTCAGGAATAAGAGGAAATGCAGAG -3'

Posted On

2015-08-18