Mutagenetix > Incidental Mutation

Incidental Mutation 'R5452:Map2k4'

432588

Institutional Source

Beutler Lab

Gene Symbol

Map2k4

Ensembl Gene

ENSMUSG00000033352

Gene Name

mitogen-activated protein kinase kinase 4

Synonyms

Serk1, Sek1, JNKK1, MKK4

MMRRC Submission

042848-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5452 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

65579069-65679123 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 65610413 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tryptophan to Arginine at position 88 (W88R)

Ref Sequence

ENSEMBL: ENSMUSP00000137819 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000046963] [ENSMUST00000125598] [ENSMUST00000130009] [ENSMUST00000138093] [ENSMUST00000140301] [ENSMUST00000152096]

AlphaFold

P47809

Predicted Effect

unknown
Transcript: ENSMUST00000046963
AA Change: V135A

SMART Domains

Protein: ENSMUSP00000041282
Gene: ENSMUSG00000033352
AA Change: V135A

Domain	Start	End	E-Value	Type
low complexity region	2	28	N/A	INTRINSIC
S_TKc	100	365	9.38e-79	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000125598
AA Change: V6A

PolyPhen 2 Score 0.765 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000137656
Gene: ENSMUSG00000033352
AA Change: V6A

Domain	Start	End	E-Value	Type
Pfam:Pkinase	34	128	8.4e-27	PFAM
Pfam:Kinase-like	36	128	8.9e-8	PFAM
Pfam:Pkinase_Tyr	37	129	6.3e-17	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000130009
AA Change: W88R

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000137819
Gene: ENSMUSG00000033352
AA Change: W88R

Domain	Start	End	E-Value	Type
low complexity region	2	28	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000138093
AA Change: V19A

PolyPhen 2 Score 0.954 (Sensitivity: 0.79; Specificity: 0.95)

Predicted Effect

unknown
Transcript: ENSMUST00000140301
AA Change: W77R

SMART Domains

Protein: ENSMUSP00000137955
Gene: ENSMUSG00000033352
AA Change: W77R

Domain	Start	End	E-Value	Type
low complexity region	2	28	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000152096
AA Change: V146A

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000114219
Gene: ENSMUSG00000033352
AA Change: V146A

Domain	Start	End	E-Value	Type
low complexity region	2	28	N/A	INTRINSIC
Pfam:Pkinase_Tyr	111	202	2.5e-9	PFAM
Pfam:Pkinase	111	204	1e-13	PFAM

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.2%
20x: 95.1%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
PHENOTYPE: Homozygotes for targeted null mutations exhibit abnormal liver development with a deficiency of parenchymal hepatocytes, severe anemia, and lethality before embryonic day 14.0. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 57 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam20	A	T	8: 41,248,801 (GRCm39)	I304F	probably damaging	Het
Adamts5	A	G	16: 85,666,800 (GRCm39)		probably benign	Het
Akr1c6	A	G	13: 4,504,544 (GRCm39)	R132G	probably benign	Het
Ash1l	T	A	3: 88,892,183 (GRCm39)	M1354K	possibly damaging	Het
C6	T	C	15: 4,844,311 (GRCm39)	I911T	possibly damaging	Het
Calm2	T	C	17: 87,743,150 (GRCm39)		probably null	Het
Ccdc80	G	A	16: 44,938,528 (GRCm39)	R745Q	probably damaging	Het
Celsr3	T	C	9: 108,721,233 (GRCm39)	I2685T	possibly damaging	Het
Chkb	T	C	15: 89,313,788 (GRCm39)		probably benign	Het
Dennd5b	T	A	6: 148,943,011 (GRCm39)		probably null	Het
Dnah2	T	C	11: 69,415,209 (GRCm39)	Y175C	probably damaging	Het
Dnajc13	A	G	9: 104,069,313 (GRCm39)	S1154P	probably benign	Het
Ephb4	T	C	5: 137,359,404 (GRCm39)	S325P	probably damaging	Het
Fzd9	C	T	5: 135,279,714 (GRCm39)	R57H	probably damaging	Het
Gemin6	T	G	17: 80,535,178 (GRCm39)	V46G	probably damaging	Het
Gm9949	A	G	18: 62,313,587 (GRCm39)		probably benign	Het
Gnb4	A	T	3: 32,643,994 (GRCm39)	M188K	probably benign	Het
Hr	G	T	14: 70,794,067 (GRCm39)	G109V	probably damaging	Het
Lrp1b	A	G	2: 40,812,328 (GRCm39)	S2426P	probably damaging	Het
Map4	C	T	9: 109,866,851 (GRCm39)		probably benign	Het
Moxd2	C	T	6: 40,859,048 (GRCm39)		probably null	Het
Mrgprx1	T	C	7: 47,671,556 (GRCm39)	I64V	probably benign	Het
Mtrex	T	C	13: 113,049,715 (GRCm39)	S232G	probably null	Het
Or5p68	A	C	7: 107,945,312 (GRCm39)	I292S	probably damaging	Het
Padi2	T	C	4: 140,659,382 (GRCm39)	F229S	probably benign	Het
Pappa2	T	C	1: 158,666,172 (GRCm39)	N1136S	probably benign	Het
Pcdhb1	A	T	18: 37,398,811 (GRCm39)	N254I	possibly damaging	Het
Plcb2	A	G	2: 118,548,727 (GRCm39)	Y400H	probably damaging	Het
Plce1	A	C	19: 38,608,926 (GRCm39)	T412P	probably benign	Het
Prg4	T	C	1: 150,331,519 (GRCm39)		probably benign	Het
Prkdc	A	G	16: 15,586,501 (GRCm39)	N2510S	possibly damaging	Het
Psme4	T	A	11: 30,741,168 (GRCm39)	S107T	probably benign	Het
Resf1	C	A	6: 149,230,611 (GRCm39)	S1219*	probably null	Het
Rint1	G	T	5: 23,999,363 (GRCm39)	A51S	probably benign	Het
Rsad1	T	A	11: 94,434,515 (GRCm39)	R306S	probably damaging	Het
Sema3c	T	G	5: 17,922,068 (GRCm39)		probably null	Het
Sirt3	G	A	7: 140,444,928 (GRCm39)	T290I	probably damaging	Het
Spam1	G	A	6: 24,800,731 (GRCm39)	G490D	probably benign	Het
Speer4f2	C	T	5: 17,581,498 (GRCm39)	R147W	possibly damaging	Het
Sppl2c	A	T	11: 104,078,126 (GRCm39)	I309L	probably benign	Het
Srxn1	G	A	2: 151,947,799 (GRCm39)	V66M	probably damaging	Het
St3gal4	C	T	9: 34,964,752 (GRCm39)	R152H	probably damaging	Het
Sv2c	A	T	13: 96,114,591 (GRCm39)	F532I	probably damaging	Het
Tacc1	C	A	8: 25,654,431 (GRCm39)	K705N	probably null	Het
Tekt3	G	T	11: 62,985,619 (GRCm39)	S475I	probably damaging	Het
Tjap1	T	C	17: 46,571,101 (GRCm39)	T139A	probably damaging	Het
Tnfrsf8	T	A	4: 145,019,214 (GRCm39)	K207M	possibly damaging	Het
Tnn	T	C	1: 159,937,831 (GRCm39)	T965A	probably benign	Het
Tns2	C	T	15: 102,017,369 (GRCm39)	R281C	probably damaging	Het
Trmt2a	A	G	16: 18,068,814 (GRCm39)	H270R	probably damaging	Het
Ttc21a	T	C	9: 119,780,037 (GRCm39)	L448P	probably benign	Het
Ttll4	C	A	1: 74,718,480 (GRCm39)	N110K	probably benign	Het
Ttn	T	A	2: 76,585,168 (GRCm39)	I22042F	probably damaging	Het
Tut7	A	G	13: 59,948,471 (GRCm39)	Y215H	probably damaging	Het
Ubr1	A	G	2: 120,698,783 (GRCm39)	Y1595H	possibly damaging	Het
Unc45a	G	A	7: 79,978,787 (GRCm39)	P621S	probably damaging	Het
Xrn2	A	T	2: 146,866,633 (GRCm39)		probably null	Het

Other mutations in Map2k4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00534:Map2k4	APN	11	65,610,305 (GRCm39)	splice site	probably benign
IGL01318:Map2k4	APN	11	65,647,089 (GRCm39)	splice site	probably benign
IGL02500:Map2k4	APN	11	65,587,136 (GRCm39)	missense	probably damaging	1.00
IGL02628:Map2k4	APN	11	65,581,567 (GRCm39)	missense	possibly damaging	0.83
IGL02873:Map2k4	APN	11	65,610,400 (GRCm39)	missense	probably damaging	0.97
IGL03124:Map2k4	APN	11	65,581,617 (GRCm39)	missense	probably damaging	0.98
R0021:Map2k4	UTSW	11	65,603,110 (GRCm39)	missense	probably damaging	1.00
R0021:Map2k4	UTSW	11	65,603,110 (GRCm39)	missense	probably damaging	1.00
R0034:Map2k4	UTSW	11	65,610,437 (GRCm39)	splice site	probably benign
R0034:Map2k4	UTSW	11	65,610,437 (GRCm39)	splice site	probably benign
R0646:Map2k4	UTSW	11	65,603,101 (GRCm39)	missense	probably damaging	1.00
R2073:Map2k4	UTSW	11	65,584,282 (GRCm39)	missense	probably damaging	0.99
R2931:Map2k4	UTSW	11	65,647,163 (GRCm39)	missense	probably damaging	0.99
R3800:Map2k4	UTSW	11	65,581,607 (GRCm39)	nonsense	probably null
R4820:Map2k4	UTSW	11	65,587,201 (GRCm39)	splice site	probably benign
R4913:Map2k4	UTSW	11	65,600,758 (GRCm39)	missense	probably damaging	1.00
R5497:Map2k4	UTSW	11	65,626,031 (GRCm39)	missense	probably damaging	1.00
R5812:Map2k4	UTSW	11	65,626,031 (GRCm39)	missense	probably damaging	1.00
R5976:Map2k4	UTSW	11	65,600,778 (GRCm39)	missense	probably benign	0.31
R6282:Map2k4	UTSW	11	65,597,842 (GRCm39)	missense	possibly damaging	0.78
R6505:Map2k4	UTSW	11	65,584,355 (GRCm39)	missense	possibly damaging	0.63
R6784:Map2k4	UTSW	11	65,582,577 (GRCm39)	unclassified	probably benign
R7560:Map2k4	UTSW	11	65,666,583 (GRCm39)	missense	unknown
R8071:Map2k4	UTSW	11	65,597,827 (GRCm39)	missense
R9092:Map2k4	UTSW	11	65,581,599 (GRCm39)	missense	probably benign
R9342:Map2k4	UTSW	11	65,581,569 (GRCm39)	missense	probably benign

Predicted Primers

PCR Primer
(F):5'- GCAAGTTAACGAGGATGGTTCTG -3'
(R):5'- GCCCTTAAAAGAATTTCTGAGTGC -3'

Sequencing Primer
(F):5'- GGTTCTGTACTATAACAAGAGGCAAC -3'
(R):5'- CTAGCCTGGTTAATATTGTGAG -3'

Posted On

2016-10-06