Mutagenetix > Incidental Mutation

Incidental Mutation 'R0588:Map4k4'

55828

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

038778-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0588 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

39940073-40065470 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 40044024 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Lysine at position 556 (Q556K)

Ref Sequence

ENSEMBL: ENSMUSP00000141862 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000163854] [ENSMUST00000168431] [ENSMUST00000191964] [ENSMUST00000192509] [ENSMUST00000195259] [ENSMUST00000195636] [ENSMUST00000195860] [ENSMUST00000193682]

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000163854
AA Change: Q687K

PolyPhen 2 Score 0.820 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: Q687K

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: Q641K

SMART Domains

Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: Q641K

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: ENSMUST00000191865
AA Change: Q44K

Predicted Effect

possibly damaging
Transcript: ENSMUST00000191964
AA Change: Q195K

PolyPhen 2 Score 0.926 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000141235
Gene: ENSMUSG00000026074
AA Change: Q195K

Domain	Start	End	E-Value	Type
low complexity region	4	28	N/A	INTRINSIC
SCOP:d1i7qa_	35	139	7e-3	SMART
low complexity region	195	206	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000192194

Predicted Effect

unknown
Transcript: ENSMUST00000192355
AA Change: Q197K

Predicted Effect

unknown
Transcript: ENSMUST00000192509
AA Change: Q633K

SMART Domains

Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: Q633K

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: ENSMUST00000195259
AA Change: Q610K

SMART Domains

Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: Q610K

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: ENSMUST00000195636
AA Change: Q610K

SMART Domains

Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: Q610K

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

possibly damaging
Transcript: ENSMUST00000195860
AA Change: Q687K

PolyPhen 2 Score 0.820 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: Q687K

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

possibly damaging
Transcript: ENSMUST00000193682
AA Change: Q556K

PolyPhen 2 Score 0.931 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: Q556K

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: ENSMUST00000195356

Meta Mutation Damage Score

0.0700

Coding Region Coverage

1x: 99.4%
3x: 98.8%
10x: 97.4%
20x: 94.8%

Validation Efficiency

100% (25/25)

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: 24 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc9	T	A	6: 142,548,787 (GRCm39)	K1299*	probably null	Het
Adamts2	G	T	11: 50,667,491 (GRCm39)	W476C	probably damaging	Het
Ankrd13c	T	C	3: 157,711,454 (GRCm39)	F525L	probably damaging	Het
Arg1	T	C	10: 24,796,522 (GRCm39)	S102G	probably damaging	Het
Atp2a3	A	T	11: 72,863,850 (GRCm39)	D192V	possibly damaging	Het
Cabin1	T	C	10: 75,581,171 (GRCm39)	E385G	possibly damaging	Het
Cacna1h	A	T	17: 25,606,538 (GRCm39)	D1020E	probably damaging	Het
Calcb	C	T	7: 114,319,361 (GRCm39)	H48Y	probably benign	Het
Crtc1	A	G	8: 70,892,199 (GRCm39)	S4P	probably damaging	Het
Dcaf6	A	G	1: 165,247,792 (GRCm39)	I147T	possibly damaging	Het
Ears2	T	C	7: 121,643,514 (GRCm39)		probably benign	Het
Fas	T	C	19: 34,304,540 (GRCm39)	V267A	probably damaging	Het
Fus	T	C	7: 127,584,746 (GRCm39)	L84P	probably damaging	Het
Fyb1	T	C	15: 6,609,940 (GRCm39)	V171A	probably benign	Het
Gdap2	T	A	3: 100,077,317 (GRCm39)	M1K	probably null	Het
Gprc5b	T	A	7: 118,583,218 (GRCm39)	Q217L	probably benign	Het
Lrrc69	A	G	4: 14,704,001 (GRCm39)	I273T	possibly damaging	Het
Npy6r	T	A	18: 44,408,888 (GRCm39)	V103E	possibly damaging	Het
Or5b24	A	G	19: 12,912,111 (GRCm39)	Y3C	probably benign	Het
Shisa9	A	G	16: 12,085,638 (GRCm39)	T416A	probably damaging	Het
Slc26a9	C	A	1: 131,681,749 (GRCm39)		probably benign	Het
Sostdc1	G	T	12: 36,367,020 (GRCm39)		probably benign	Het
St18	T	A	1: 6,887,962 (GRCm39)	F510L	probably damaging	Het
Zdhhc7	A	G	8: 120,810,106 (GRCm39)		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
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
R2987:Map4k4	UTSW	1	40,025,925 (GRCm39)	missense	probably damaging	1.00
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'- CCCGCTTCAGTCCAAACATGACTTC -3'
(R):5'- CTGATCAATAACGCTGCTGCTGC -3'

Sequencing Primer
(F):5'- TGACTTCAGCATGACAGGACTG -3'
(R):5'- tgtgtgtgtgagtgtgagtg -3'

Posted On

2013-07-11