Mutagenetix > Incidental Mutations

Incidental Mutation 'R4715:Map4k4'

353913

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

041982-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4715 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

39900913-40026310 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 40019564 bp

Zygosity

Heterozygous

Amino Acid Change

Valine to Isoleucine at position 1040 (V1040I)

Ref Sequence

ENSEMBL: ENSMUSP00000126961 (fasta)

Gene Model

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000163854
AA Change: V1040I

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

SMART Domains

Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: V1040I

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: V990I

SMART Domains

Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: V990I

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: ENSMUST00000191657

Predicted Effect

unknown
Transcript: ENSMUST00000192509
AA Change: V986I

SMART Domains

Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: V986I

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: ENSMUST00000192884

Predicted Effect

possibly damaging
Transcript: ENSMUST00000193682
AA Change: V973I

PolyPhen 2 Score 0.511 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: V973I

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

unknown
Transcript: ENSMUST00000195259
AA Change: V960I

SMART Domains

Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: V960I

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: V1024I

SMART Domains

Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: V1024I

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

probably damaging
Transcript: ENSMUST00000195860
AA Change: V1040I

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: V1040I

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

Meta Mutation Damage Score

0.1046

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 95.0%

Validation Efficiency

92% (86/93)

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: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc2	A	C	19: 43,816,882	E725A	possibly damaging	Het
Abcc5	G	T	16: 20,398,876	L362I	probably damaging	Het
Ammecr1l	C	T	18: 31,774,653	R179*	probably null	Het
Arap2	G	T	5: 62,749,094	T194K	probably benign	Het
Atf2	C	A	2: 73,823,300	V282F	probably damaging	Het
Atp1a1	T	C	3: 101,591,806	E159G	possibly damaging	Het
B4galt2	T	C	4: 117,877,179	S258G	possibly damaging	Het
Bptf	G	T	11: 107,047,181	H2695N	probably damaging	Het
Casq2	T	C	3: 102,110,244	V80A	probably benign	Het
Ccdc130	A	G	8: 84,263,874	I43T	probably damaging	Het
Cdc42ep3	G	A	17: 79,335,458	A11V	probably benign	Het
Cdh4	A	T	2: 179,780,467	H128L	probably benign	Het
Cdk5rap1	C	A	2: 154,361,835	*191L	probably null	Het
Cfdp1	G	A	8: 111,830,891	T206I	probably benign	Het
Cgn	C	A	3: 94,779,438	G185W	probably damaging	Het
Clpx	A	C	9: 65,312,114	R231S	possibly damaging	Het
Copg1	T	A	6: 87,912,286	L870*	probably null	Het
Cyp4a10	A	T	4: 115,525,338	D275V	probably benign	Het
Dip2a	T	C	10: 76,296,406	T504A	probably benign	Het
Dmxl2	A	C	9: 54,446,405		probably null	Het
Dnaaf5	A	T	5: 139,178,000	I671F	probably damaging	Het
Dnah14	A	G	1: 181,757,223	D3173G	probably damaging	Het
Dock2	T	C	11: 34,294,118	Y1074C	probably damaging	Het
Dthd1	A	C	5: 62,888,187	M765L	probably benign	Het
E2f3	A	C	13: 29,911,275	C220W	probably damaging	Het
Elf3	C	T	1: 135,257,752	S8N	probably damaging	Het
F2rl1	A	T	13: 95,513,267	V369E	probably damaging	Het
Fam214a	T	A	9: 75,012,968	W799R	probably damaging	Het
Fpr-rs7	C	T	17: 20,113,428	G267R	probably benign	Het
Ggact	A	T	14: 122,891,635	L56Q	possibly damaging	Het
Gm10698	A	T	9: 33,728,488		noncoding transcript	Het
Gm5546	T	C	3: 104,366,508		noncoding transcript	Het
Gm8267	A	G	14: 44,717,835	V243A	probably benign	Het
Gtf2h1	A	G	7: 46,815,412	T424A	possibly damaging	Het
Gucy1b2	A	G	14: 62,423,017	V140A	possibly damaging	Het
Htatip2	T	C	7: 49,770,844	L146P	probably damaging	Het
Htr1b	T	C	9: 81,631,510	D348G	possibly damaging	Het
Ifi205	T	C	1: 174,028,321	I48V	possibly damaging	Het
Igkv18-36	C	T	6: 69,992,591	R72K	probably damaging	Het
Kcnk7	T	C	19: 5,706,253	L169P	probably damaging	Het
Klf17	T	C	4: 117,760,536	D208G	probably benign	Het
Ltn1	A	G	16: 87,418,494	F418L	probably damaging	Het
Mark1	A	G	1: 184,912,132	V445A	probably benign	Het
Med11	T	C	11: 70,453,196	I114T	probably benign	Het
Moxd2	A	G	6: 40,887,247	V83A	probably damaging	Het
Mrpl33	A	G	5: 31,616,358		probably benign	Het
Mrps27	A	G	13: 99,414,815		probably null	Het
Nop58	T	C	1: 59,696,026	V75A	probably benign	Het
Olfr1290	A	C	2: 111,489,744	M138R	probably benign	Het
Olfr1339	T	C	4: 118,734,655	L42P	probably damaging	Het
Olfr136	A	C	17: 38,335,840	I228L	possibly damaging	Het
Olfr325	A	G	11: 58,581,429	D195G	probably damaging	Het
Olfr832	A	G	9: 18,945,446	H266R	probably benign	Het
Olfr844	C	A	9: 19,319,147	F210L	probably benign	Het
Pdzd2	G	T	15: 12,419,516	N263K	possibly damaging	Het
Podnl1	C	A	8: 84,126,061		probably benign	Het
Prkd3	G	T	17: 78,951,937	H864N	possibly damaging	Het
Ptprd	T	C	4: 76,107,333	T543A	probably benign	Het
Pum2	T	A	12: 8,747,272	I788N	probably damaging	Het
Ralgapa1	T	A	12: 55,693,458	N1328I	probably damaging	Het
Rhoc	T	C	3: 104,794,039	L193P	probably damaging	Het
Rif1	T	C	2: 52,073,139		probably benign	Het
Rspo2	A	T	15: 43,075,904	C163*	probably null	Het
Sco1	A	G	11: 67,056,599	Y204C	probably damaging	Het
Shc2	T	C	10: 79,622,379	K490R	probably benign	Het
Siglec1	T	C	2: 131,074,436	D1198G	probably damaging	Het
Slc25a18	T	C	6: 120,786,090	V31A	probably damaging	Het
Smpd5	A	T	15: 76,295,693	I112L	probably benign	Het
Synpr	CT	C	14: 13,285,198		probably null	Het
Tdrd9	T	G	12: 112,041,689	S988A	probably benign	Het
Tiam2	T	A	17: 3,454,168	F982I	probably damaging	Het
Tmc3	G	A	7: 83,622,396	V919I	probably benign	Het
Tmem200c	A	T	17: 68,840,470	D16V	probably damaging	Het
Tmem37	A	T	1: 120,068,205	D47E	probably damaging	Het
Top3a	T	A	11: 60,742,997	R733*	probably null	Het
Treh	T	C	9: 44,683,318	V8A	probably benign	Het
Trim17	A	C	11: 58,968,450		probably benign	Het
Ubash3b	T	C	9: 41,016,600	K471E	probably damaging	Het
Usp8	T	A	2: 126,729,222	L144Q	possibly damaging	Het
Wnk2	T	A	13: 49,147,232	M1L	unknown	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
R4304:Map4k4	UTSW	1	39973972	missense	possibly damaging	0.74
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
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'- GTGTGTGCCTCTGTTTCTCA -3'
(R):5'- AGTTTCATACAGCCCAGTAACT -3'

Sequencing Primer
(F):5'- TTGATGCACACAGATAGCTTGGC -3'
(R):5'- CTTAAACCTGACTCTAATGGAACTC -3'

Posted On

2015-10-21