Mutagenetix > Incidental Mutation

Incidental Mutation 'R2987:Map4k4'

257810

Institutional Source

Beutler Lab

Gene Symbol

Map4k4

Ensembl Gene

ENSMUSG00000026074

Gene Name

mitogen-activated protein kinase kinase kinase kinase 4

Synonyms

9430080K19Rik, Nik

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2987 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

39940073-40065470 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 40025925 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Arginine at position 305 (H305R)

Ref Sequence

ENSEMBL: ENSMUSP00000141613 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

unknown
Transcript: ENSMUST00000163854
AA Change: H305R

SMART Domains

Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: H305R

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

unknown
Transcript: ENSMUST00000168431
AA Change: H305R

SMART Domains

Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: H305R

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

possibly damaging
Transcript: ENSMUST00000191761
AA Change: H305R

PolyPhen 2 Score 0.899 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000141332
Gene: ENSMUSG00000026074
AA Change: H305R

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

probably damaging
Transcript: ENSMUST00000192509
AA Change: H305R

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

SMART Domains

Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: H305R

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: H305R

SMART Domains

Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: H305R

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

probably damaging
Transcript: ENSMUST00000195259
AA Change: H305R

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: H305R

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

unknown
Transcript: ENSMUST00000195860
AA Change: H305R

SMART Domains

Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: H305R

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

probably damaging
Transcript: ENSMUST00000195636
AA Change: H305R

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

SMART Domains

Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: H305R

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

Coding Region Coverage

1x: 99.4%
3x: 98.7%
10x: 97.2%
20x: 94.5%

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: 22 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrf3	T	C	5: 30,402,358 (GRCm39)	I557V	probably damaging	Het
Bag6	T	A	17: 35,364,661 (GRCm39)	L983*	probably null	Het
Clcn1	A	G	6: 42,275,784 (GRCm39)	Y302C	probably damaging	Het
Dlc1	A	T	8: 37,041,306 (GRCm39)	C1308S	probably damaging	Het
Ebna1bp2	A	G	4: 118,478,133 (GRCm39)	D2G	probably damaging	Het
Exoc6b	T	A	6: 84,828,929 (GRCm39)	K485I	probably damaging	Het
Galnt3	C	T	2: 65,914,585 (GRCm39)	E611K	probably benign	Het
Gm5901	A	G	7: 105,026,507 (GRCm39)	I92V	probably benign	Het
Kcnh8	A	T	17: 53,263,763 (GRCm39)	L753F	probably benign	Het
L3mbtl4	T	C	17: 68,666,513 (GRCm39)	S14P	possibly damaging	Het
Nid1	A	T	13: 13,674,258 (GRCm39)	Y879F	probably benign	Het
Nsf	A	T	11: 103,749,869 (GRCm39)		probably null	Het
Olfml2a	G	A	2: 38,837,306 (GRCm39)	V150M	probably damaging	Het
Or51a24	A	G	7: 103,734,077 (GRCm39)	V70A	probably benign	Het
Pkhd1	A	T	1: 20,174,823 (GRCm39)	D3744E	possibly damaging	Het
Pla1a	A	T	16: 38,228,104 (GRCm39)	C258S	probably damaging	Het
Plk2	A	T	13: 110,534,243 (GRCm39)	R274S	probably benign	Het
Sumf2	T	C	5: 129,875,925 (GRCm39)	L30P	possibly damaging	Het
Synpo2	T	C	3: 122,910,622 (GRCm39)	H341R	probably damaging	Het
Trbv12-1	G	A	6: 41,090,840 (GRCm39)	E71K	probably benign	Het
Usp17lc	T	C	7: 103,067,509 (GRCm39)	V268A	probably damaging	Het
Vmn1r36	A	T	6: 66,693,700 (GRCm39)	H21Q	probably benign	Het

Other mutations in Map4k4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00328:Map4k4	APN	1	40,043,976 (GRCm39)	missense	probably damaging	0.99
IGL00417:Map4k4	APN	1	40,053,692 (GRCm39)	missense	possibly damaging	0.92
IGL00516:Map4k4	APN	1	40,053,762 (GRCm39)	missense	probably damaging	1.00
IGL01545:Map4k4	APN	1	40,053,389 (GRCm39)	splice site	probably benign
IGL02092:Map4k4	APN	1	40,063,508 (GRCm39)	missense	probably damaging	1.00
IGL02092:Map4k4	APN	1	40,025,943 (GRCm39)	missense	probably benign	0.12
IGL02570:Map4k4	APN	1	40,019,739 (GRCm39)	missense	probably benign	0.06
IGL02626:Map4k4	APN	1	40,053,257 (GRCm39)	splice site	probably benign
IGL02993:Map4k4	APN	1	40,053,348 (GRCm39)	missense	probably damaging	0.98
IGL03178:Map4k4	APN	1	40,025,853 (GRCm39)	missense	possibly damaging	0.63
tank	UTSW	1	40,044,024 (GRCm39)	missense	possibly damaging	0.93
IGL02835:Map4k4	UTSW	1	40,049,760 (GRCm39)	missense	probably damaging	0.99
R0496:Map4k4	UTSW	1	40,045,982 (GRCm39)	missense	probably damaging	0.99
R0498:Map4k4	UTSW	1	40,029,338 (GRCm39)	missense	probably benign	0.22
R0588:Map4k4	UTSW	1	40,044,024 (GRCm39)	missense	possibly damaging	0.93
R0674:Map4k4	UTSW	1	40,042,975 (GRCm39)	missense	probably damaging	1.00
R1205:Map4k4	UTSW	1	40,043,004 (GRCm39)	missense	probably damaging	1.00
R1349:Map4k4	UTSW	1	40,060,319 (GRCm39)	missense	probably damaging	1.00
R1615:Map4k4	UTSW	1	40,045,990 (GRCm39)	splice site	probably benign
R1763:Map4k4	UTSW	1	40,039,917 (GRCm39)	splice site	probably benign
R1800:Map4k4	UTSW	1	40,062,620 (GRCm39)	missense	probably damaging	1.00
R1893:Map4k4	UTSW	1	40,040,717 (GRCm39)	missense	probably benign	0.08
R2411:Map4k4	UTSW	1	40,046,656 (GRCm39)	missense	probably damaging	0.96
R2851:Map4k4	UTSW	1	40,039,915 (GRCm39)	splice site	probably benign
R2852:Map4k4	UTSW	1	40,039,915 (GRCm39)	splice site	probably benign
R3087:Map4k4	UTSW	1	40,060,242 (GRCm39)	critical splice acceptor site	probably null
R3688:Map4k4	UTSW	1	40,024,331 (GRCm39)	splice site	probably null
R4075:Map4k4	UTSW	1	40,062,622 (GRCm39)	missense	probably damaging	0.96
R4304:Map4k4	UTSW	1	40,013,132 (GRCm39)	missense	possibly damaging	0.74
R4564:Map4k4	UTSW	1	40,028,135 (GRCm39)	missense	probably damaging	1.00
R4569:Map4k4	UTSW	1	40,039,698 (GRCm39)	missense	probably damaging	1.00
R4613:Map4k4	UTSW	1	40,056,351 (GRCm39)	missense	probably benign	0.05
R4715:Map4k4	UTSW	1	40,058,724 (GRCm39)	missense	probably damaging	1.00
R4788:Map4k4	UTSW	1	40,043,076 (GRCm39)	missense	probably benign	0.01
R4926:Map4k4	UTSW	1	40,056,385 (GRCm39)	missense	probably damaging	1.00
R4943:Map4k4	UTSW	1	40,058,754 (GRCm39)	missense	probably damaging	0.99
R5033:Map4k4	UTSW	1	40,046,662 (GRCm39)	missense	probably damaging	0.99
R5177:Map4k4	UTSW	1	40,025,922 (GRCm39)	missense	probably damaging	1.00
R5297:Map4k4	UTSW	1	40,001,377 (GRCm39)	missense	probably damaging	1.00
R5844:Map4k4	UTSW	1	40,039,036 (GRCm39)	splice site	probably benign
R5952:Map4k4	UTSW	1	40,039,082 (GRCm39)	unclassified	probably benign
R6111:Map4k4	UTSW	1	40,050,822 (GRCm39)	missense	probably benign	0.00
R6125:Map4k4	UTSW	1	40,043,125 (GRCm39)	missense	possibly damaging	0.77
R6838:Map4k4	UTSW	1	40,015,882 (GRCm39)	missense	probably damaging	1.00
R6927:Map4k4	UTSW	1	40,050,842 (GRCm39)	missense	probably benign	0.00
R7008:Map4k4	UTSW	1	40,028,131 (GRCm39)	missense	probably benign	0.44
R7164:Map4k4	UTSW	1	40,013,132 (GRCm39)	missense	possibly damaging	0.74
R7195:Map4k4	UTSW	1	40,058,829 (GRCm39)	missense	possibly damaging	0.93
R7352:Map4k4	UTSW	1	40,001,387 (GRCm39)	missense	unknown
R7589:Map4k4	UTSW	1	40,060,251 (GRCm39)	nonsense	probably null
R7816:Map4k4	UTSW	1	40,053,368 (GRCm39)	missense	possibly damaging	0.53
R7869:Map4k4	UTSW	1	40,013,204 (GRCm39)	missense	unknown
R8013:Map4k4	UTSW	1	40,001,372 (GRCm39)	missense	unknown
R8145:Map4k4	UTSW	1	40,039,694 (GRCm39)	missense
R8154:Map4k4	UTSW	1	40,060,302 (GRCm39)	nonsense	probably null
R8254:Map4k4	UTSW	1	40,045,835 (GRCm39)	missense	probably damaging	0.99
R8266:Map4k4	UTSW	1	40,050,813 (GRCm39)	missense	possibly damaging	0.53
R8375:Map4k4	UTSW	1	40,063,801 (GRCm39)	missense	possibly damaging	0.73
R8487:Map4k4	UTSW	1	40,028,136 (GRCm39)	missense	probably damaging	1.00
R8699:Map4k4	UTSW	1	40,015,910 (GRCm39)	missense	unknown
R8726:Map4k4	UTSW	1	40,043,142 (GRCm39)	missense	possibly damaging	0.95
R8907:Map4k4	UTSW	1	40,058,770 (GRCm39)	missense	probably damaging	0.97
R8956:Map4k4	UTSW	1	40,039,840 (GRCm39)	missense	probably benign	0.11
R8963:Map4k4	UTSW	1	40,039,740 (GRCm39)	missense	probably damaging	1.00
R9091:Map4k4	UTSW	1	40,042,923 (GRCm39)	missense	probably benign	0.02
R9234:Map4k4	UTSW	1	40,029,261 (GRCm39)	missense	unknown
R9270:Map4k4	UTSW	1	40,042,923 (GRCm39)	missense	probably benign	0.02
R9438:Map4k4	UTSW	1	40,045,952 (GRCm39)	missense	probably damaging	0.99
R9689:Map4k4	UTSW	1	40,058,722 (GRCm39)	missense	possibly damaging	0.95
R9771:Map4k4	UTSW	1	40,025,877 (GRCm39)	missense	unknown

Predicted Primers

PCR Primer
(F):5'- ATGGTTTTCAGGCTCGTCAC -3'
(R):5'- AGCATCCAGTGGTCTTGCTC -3'

Sequencing Primer
(F):5'- CAGGCTCGTCACCAGTATTTTTGAG -3'
(R):5'- CAAGTGTGCAGGAAAGCCC -3'

Posted On

2015-01-11