Mutagenetix > Incidental Mutations

Incidental Mutation 'R4304:Map4k4'

322522

Institutional Source

Beutler Lab

Gene Symbol

Map4k4

Ensembl Gene

ENSMUSG00000026074

Gene Name

mitogen-activated protein kinase kinase kinase kinase 4

Synonyms

9430080K19Rik, Nik

MMRRC Submission

040865-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4304 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

39900913-40026310 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 39973972 bp

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 76 (Y76H)

Ref Sequence

ENSEMBL: ENSMUSP00000141613 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000163854] [ENSMUST00000168431] [ENSMUST00000191761] [ENSMUST00000192509] [ENSMUST00000193682] [ENSMUST00000195259] [ENSMUST00000195636] [ENSMUST00000195860]

Predicted Effect

unknown
Transcript: ENSMUST00000163854
AA Change: Y76H

SMART Domains

Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: Y76H

Domain	Start	End	E-Value	Type
S_TKc	25	289	6.87e-95	SMART
low complexity region	318	342	N/A	INTRINSIC
coiled coil region	357	494	N/A	INTRINSIC
low complexity region	503	512	N/A	INTRINSIC
low complexity region	687	698	N/A	INTRINSIC
low complexity region	721	747	N/A	INTRINSIC
low complexity region	754	763	N/A	INTRINSIC
low complexity region	811	837	N/A	INTRINSIC
low complexity region	891	904	N/A	INTRINSIC
low complexity region	919	929	N/A	INTRINSIC
CNH	970	1268	2.76e-127	SMART

Predicted Effect

SMART Domains

Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: Y76H

Domain	Start	End	E-Value	Type
S_TKc	25	289	6.87e-95	SMART
low complexity region	318	342	N/A	INTRINSIC
coiled coil region	357	494	N/A	INTRINSIC
low complexity region	503	512	N/A	INTRINSIC
low complexity region	633	644	N/A	INTRINSIC
low complexity region	667	693	N/A	INTRINSIC
low complexity region	700	709	N/A	INTRINSIC
low complexity region	757	783	N/A	INTRINSIC
low complexity region	837	850	N/A	INTRINSIC
low complexity region	865	875	N/A	INTRINSIC
CNH	916	1214	2.76e-127	SMART

Predicted Effect

unknown
Transcript: ENSMUST00000191761
AA Change: Y76H

SMART Domains

Protein: ENSMUSP00000141332
Gene: ENSMUSG00000026074
AA Change: Y76H

Domain	Start	End	E-Value	Type
S_TKc	25	289	3.4e-97	SMART
low complexity region	318	342	N/A	INTRINSIC
coiled coil region	357	404	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000192509
AA Change: Y76H

PolyPhen 2 Score 0.739 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: Y76H

Domain	Start	End	E-Value	Type
S_TKc	25	289	6.87e-95	SMART
low complexity region	318	342	N/A	INTRINSIC
coiled coil region	357	494	N/A	INTRINSIC
low complexity region	503	512	N/A	INTRINSIC
low complexity region	633	644	N/A	INTRINSIC
low complexity region	667	693	N/A	INTRINSIC
low complexity region	700	709	N/A	INTRINSIC
low complexity region	757	783	N/A	INTRINSIC
low complexity region	837	850	N/A	INTRINSIC
low complexity region	865	875	N/A	INTRINSIC
CNH	916	1214	2.76e-127	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000193514

Predicted Effect

unknown
Transcript: ENSMUST00000193682
AA Change: Y76H

SMART Domains

Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: Y76H

Domain	Start	End	E-Value	Type
S_TKc	25	289	6.87e-95	SMART
low complexity region	318	342	N/A	INTRINSIC
coiled coil region	357	494	N/A	INTRINSIC
low complexity region	503	512	N/A	INTRINSIC
low complexity region	556	567	N/A	INTRINSIC
low complexity region	590	616	N/A	INTRINSIC
low complexity region	623	632	N/A	INTRINSIC
low complexity region	680	706	N/A	INTRINSIC
low complexity region	785	814	N/A	INTRINSIC
low complexity region	824	837	N/A	INTRINSIC
low complexity region	852	862	N/A	INTRINSIC
CNH	903	1201	2.76e-127	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000194163

Predicted Effect

possibly damaging
Transcript: ENSMUST00000195259
AA Change: Y76H

PolyPhen 2 Score 0.562 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: Y76H

Domain	Start	End	E-Value	Type
S_TKc	25	289	6.87e-95	SMART
low complexity region	318	342	N/A	INTRINSIC
coiled coil region	357	494	N/A	INTRINSIC
low complexity region	503	512	N/A	INTRINSIC
low complexity region	610	621	N/A	INTRINSIC
low complexity region	644	670	N/A	INTRINSIC
low complexity region	677	686	N/A	INTRINSIC
low complexity region	731	757	N/A	INTRINSIC
low complexity region	811	824	N/A	INTRINSIC
low complexity region	839	849	N/A	INTRINSIC
CNH	890	1188	2.76e-127	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000195636
AA Change: Y76H

PolyPhen 2 Score 0.739 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: Y76H

Domain	Start	End	E-Value	Type
S_TKc	25	289	3.4e-97	SMART
low complexity region	318	342	N/A	INTRINSIC
coiled coil region	357	494	N/A	INTRINSIC
low complexity region	503	512	N/A	INTRINSIC
low complexity region	610	621	N/A	INTRINSIC
low complexity region	644	670	N/A	INTRINSIC
low complexity region	677	686	N/A	INTRINSIC
low complexity region	731	757	N/A	INTRINSIC
low complexity region	836	865	N/A	INTRINSIC
low complexity region	875	888	N/A	INTRINSIC
low complexity region	903	913	N/A	INTRINSIC
CNH	954	1252	1.4e-129	SMART

Predicted Effect

unknown
Transcript: ENSMUST00000195860
AA Change: Y76H

SMART Domains

Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: Y76H

Domain	Start	End	E-Value	Type
S_TKc	25	289	6.87e-95	SMART
low complexity region	318	342	N/A	INTRINSIC
coiled coil region	357	494	N/A	INTRINSIC
low complexity region	503	512	N/A	INTRINSIC
low complexity region	687	698	N/A	INTRINSIC
low complexity region	721	747	N/A	INTRINSIC
low complexity region	754	763	N/A	INTRINSIC
low complexity region	811	837	N/A	INTRINSIC
low complexity region	891	904	N/A	INTRINSIC
low complexity region	919	929	N/A	INTRINSIC
CNH	970	1268	2.76e-127	SMART

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.4%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die as embryos around day E9.5-10.5. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 30 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810474O19Rik	C	T	6: 149,326,238	Q261*	probably null	Het
Adam32	A	T	8: 24,901,529	M323K	probably damaging	Het
Arhgap42	A	G	9: 9,006,488	S636P	probably benign	Het
Arhgef5	C	T	6: 43,279,498	A1180V	probably damaging	Het
Cep152	G	A	2: 125,563,723	Q1630*	probably null	Het
Cfap157	G	A	2: 32,779,042	R350W	probably damaging	Het
Csgalnact1	A	T	8: 68,372,642	V400D	possibly damaging	Het
Fig4	T	A	10: 41,256,427	D461V	probably benign	Het
Frmd4a	C	T	2: 4,333,078	R32C	probably benign	Het
Gcfc2	G	A	6: 81,943,007	R397Q	probably damaging	Het
Gm20939	A	C	17: 94,877,281	Q452H	probably benign	Het
Gm5592	A	T	7: 41,286,262	M63L	probably benign	Het
Gm7173	C	G	X: 79,498,029	K469N	probably damaging	Het
H2-M3	T	C	17: 37,272,404	M252T	probably benign	Het
Lsm14a	C	A	7: 34,357,433		probably null	Het
Npc1	C	T	18: 12,210,527	A470T	possibly damaging	Het
Oit1	G	A	14: 8,349,324	P209S	probably damaging	Het
Olfr1240	A	T	2: 89,440,198	V27D	probably damaging	Het
Prr27	A	G	5: 87,842,907	H126R	probably benign	Het
Rptn	C	A	3: 93,396,931	H524N	probably benign	Het
Slc4a11	A	T	2: 130,688,138	M240K	probably benign	Het
Smg1	T	C	7: 118,139,518	I3503V	probably benign	Het
Snx13	A	G	12: 35,122,942	K625E	probably benign	Het
Stk10	T	C	11: 32,610,634	V663A	probably damaging	Het
Tex11	C	A	X: 100,933,415	A487S	possibly damaging	Het
Tpp1	T	A	7: 105,750,309	D84V	possibly damaging	Het
Vmn1r238	T	A	18: 3,123,040	R125*	probably null	Het
Vmn2r12	A	G	5: 109,086,006	L780P	probably damaging	Het
Wfdc15b	A	C	2: 164,215,468	M1R	probably null	Het
Wnk2	C	T	13: 49,090,837	D508N	probably damaging	Het

Other mutations in Map4k4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00328:Map4k4	APN	1	40004816	missense	probably damaging	0.99
IGL00417:Map4k4	APN	1	40014532	missense	possibly damaging	0.92
IGL00516:Map4k4	APN	1	40014602	missense	probably damaging	1.00
IGL01545:Map4k4	APN	1	40014229	splice site	probably benign
IGL02092:Map4k4	APN	1	39986783	missense	probably benign	0.12
IGL02092:Map4k4	APN	1	40024348	missense	probably damaging	1.00
IGL02570:Map4k4	APN	1	39980579	missense	probably benign	0.06
IGL02626:Map4k4	APN	1	40014097	splice site	probably benign
IGL02993:Map4k4	APN	1	40014188	missense	probably damaging	0.98
IGL03178:Map4k4	APN	1	39986693	missense	possibly damaging	0.63
tank	UTSW	1	40004864	missense	possibly damaging	0.93
IGL02835:Map4k4	UTSW	1	40010600	missense	probably damaging	0.99
R0496:Map4k4	UTSW	1	40006822	missense	probably damaging	0.99
R0498:Map4k4	UTSW	1	39990178	missense	probably benign	0.22
R0588:Map4k4	UTSW	1	40004864	missense	possibly damaging	0.93
R0674:Map4k4	UTSW	1	40003815	missense	probably damaging	1.00
R1205:Map4k4	UTSW	1	40003844	missense	probably damaging	1.00
R1349:Map4k4	UTSW	1	40021159	missense	probably damaging	1.00
R1615:Map4k4	UTSW	1	40006830	splice site	probably benign
R1763:Map4k4	UTSW	1	40000757	splice site	probably benign
R1800:Map4k4	UTSW	1	40023460	missense	probably damaging	1.00
R1893:Map4k4	UTSW	1	40001557	missense	probably benign	0.08
R2411:Map4k4	UTSW	1	40007496	missense	probably damaging	0.96
R2851:Map4k4	UTSW	1	40000755	splice site	probably benign
R2852:Map4k4	UTSW	1	40000755	splice site	probably benign
R2987:Map4k4	UTSW	1	39986765	missense	probably damaging	1.00
R3087:Map4k4	UTSW	1	40021082	critical splice acceptor site	probably null
R3688:Map4k4	UTSW	1	39985171	splice site	probably null
R4075:Map4k4	UTSW	1	40023462	missense	probably damaging	0.96
R4564:Map4k4	UTSW	1	39988975	missense	probably damaging	1.00
R4569:Map4k4	UTSW	1	40000538	missense	probably damaging	1.00
R4613:Map4k4	UTSW	1	40017191	missense	probably benign	0.05
R4715:Map4k4	UTSW	1	40019564	missense	probably damaging	1.00
R4788:Map4k4	UTSW	1	40003916	missense	probably benign	0.01
R4926:Map4k4	UTSW	1	40017225	missense	probably damaging	1.00
R4943:Map4k4	UTSW	1	40019594	missense	probably damaging	0.99
R5033:Map4k4	UTSW	1	40007502	missense	probably damaging	0.99
R5177:Map4k4	UTSW	1	39986762	missense	probably damaging	1.00
R5297:Map4k4	UTSW	1	39962217	missense	probably damaging	1.00
R5844:Map4k4	UTSW	1	39999876	splice site	probably benign
R5952:Map4k4	UTSW	1	39999922	unclassified	probably benign
R6111:Map4k4	UTSW	1	40011662	missense	probably benign	0.00
R6125:Map4k4	UTSW	1	40003965	missense	possibly damaging	0.77
R6838:Map4k4	UTSW	1	39976722	missense	probably damaging	1.00
R6927:Map4k4	UTSW	1	40011682	missense	probably benign	0.00
R7008:Map4k4	UTSW	1	39988971	missense	probably benign	0.44
R7164:Map4k4	UTSW	1	39973972	missense	possibly damaging	0.74
R7195:Map4k4	UTSW	1	40019669	missense	possibly damaging	0.93
R7352:Map4k4	UTSW	1	39962227	missense	unknown
R7589:Map4k4	UTSW	1	40021091	nonsense	probably null
R7816:Map4k4	UTSW	1	40014208	missense	possibly damaging	0.53
R7869:Map4k4	UTSW	1	39974044	missense	unknown
R8013:Map4k4	UTSW	1	39962212	missense	unknown
R8145:Map4k4	UTSW	1	40000534	missense
R8154:Map4k4	UTSW	1	40021142	nonsense	probably null
R8254:Map4k4	UTSW	1	40006675	missense	probably damaging	0.99
R8266:Map4k4	UTSW	1	40011653	missense	possibly damaging	0.53
R8375:Map4k4	UTSW	1	40024641	missense	possibly damaging	0.73
R8487:Map4k4	UTSW	1	39988976	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CCCGTGGTCATATTCAGAAGG -3'
(R):5'- TCTTTGCTACAGTGCAGACAGG -3'

Sequencing Primer
(F):5'- TCAGAAGGCTGAGCTGTGG -3'
(R):5'- TAGGGAAGCTGCTGTCCC -3'

Posted On

2015-06-20