Mutagenetix > Incidental Mutation

Incidental Mutation 'R7164:Map4k4'

557772

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7164 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

39900913-40026310 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 39973972 bp (GRCm38)

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]

AlphaFold

no structure available at present

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: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

Validation Efficiency

100% (59/59)

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: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610037L13Rik	C	A	4: 107,894,890	D155E	not run	Het
4932415D10Rik	G	A	10: 82,286,229	T3649I	probably damaging	Het
Actn2	G	A	13: 12,278,961	H558Y	probably damaging	Het
Akap9	G	C	5: 4,060,364	E3022D	probably damaging	Het
Anapc2	C	T	2: 25,284,999	R710C	probably damaging	Het
Bcl6	G	A	16: 23,966,226	R675*	probably null	Het
Carmil3	A	G	14: 55,501,282	E844G	probably damaging	Het
Cdk17	T	G	10: 93,232,481	S367A	probably benign	Het
Cfap206	T	A	4: 34,719,656	M253L	probably benign	Het
Chd3	T	G	11: 69,362,306	K228Q	probably damaging	Het
Cit	T	A	5: 115,985,787	I1503N	possibly damaging	Het
Csn1s1	A	G	5: 87,674,228	N119S	possibly damaging	Het
Degs1	A	G	1: 182,279,125	S226P	probably damaging	Het
Espl1	T	C	15: 102,313,203	W976R	probably damaging	Het
Fbxl4	C	T	4: 22,386,218	P275L	probably benign	Het
Flnb	A	G	14: 7,915,944		probably null	Het
Gm996	T	A	2: 25,578,567	H444L	possibly damaging	Het
Gnptab	T	A	10: 88,434,070	Y878*	probably null	Het
Gpr89	A	T	3: 96,871,398	M453K	probably benign	Het
Igsf5	A	T	16: 96,372,848	Q26L	possibly damaging	Het
Inpp5e	T	A	2: 26,407,983	D202V	possibly damaging	Het
Itga3	C	T	11: 95,052,479	V931M	possibly damaging	Het
Kcnab3	T	C	11: 69,331,358		probably null	Het
Klk4	T	C	7: 43,881,698	I17T	possibly damaging	Het
Lrrc73	T	C	17: 46,256,243	L206P	probably damaging	Het
Manba	A	T	3: 135,542,388	N346I	probably damaging	Het
Map4k5	T	C	12: 69,830,436	T312A	probably benign	Het
Masp2	A	G	4: 148,610,115		probably null	Het
Mast1	T	C	8: 84,935,304	D63G	possibly damaging	Het
Mtf2	T	A	5: 108,093,369	S254T	possibly damaging	Het
Myo16	A	T	8: 10,569,585	T1379S	unknown	Het
Myo5a	A	G	9: 75,180,153	E1097G	probably benign	Het
Nat1	T	C	8: 67,491,677	V238A	possibly damaging	Het
Nhlrc2	A	G	19: 56,592,499	D493G	probably damaging	Het
Olfr1165-ps	T	C	2: 88,101,832	K52E	probably damaging	Het
Olfr1331	C	T	4: 118,869,725	P315S	probably benign	Het
Olfr1462	A	T	19: 13,190,906	M80L	probably benign	Het
Olfr291	A	G	7: 84,857,043	I227V	possibly damaging	Het
Olfr50	T	C	2: 36,793,697	S154P	probably benign	Het
Olfr919	A	G	9: 38,698,219	I49T	possibly damaging	Het
Pcsk5	C	T	19: 17,451,985	C1543Y	probably damaging	Het
Pde4d	A	G	13: 109,032,688	D88G	probably benign	Het
Pld5	A	T	1: 176,213,621	M1K	probably null	Het
Prmt6	A	G	3: 110,250,364	M203T	probably benign	Het
Prr14l	A	T	5: 32,829,166	V995D	probably damaging	Het
Psg18	T	C	7: 18,350,937	E199G	possibly damaging	Het
Pth1r	A	G	9: 110,723,747	I439T	possibly damaging	Het
Ptprc	T	A	1: 138,117,862	I87F	probably benign	Het
Slc44a1	T	C	4: 53,528,711	S154P	probably benign	Het
Slco1c1	T	A	6: 141,542,129	Y192*	probably null	Het
Spag16	A	G	1: 70,724,866	H615R	possibly damaging	Het
Tas2r114	G	A	6: 131,689,765	A100V	possibly damaging	Het
U2af1l4	T	C	7: 30,565,119	S103P	probably benign	Het
Usp10	T	C	8: 119,942,108	S383P	probably damaging	Het
Vmn2r113	A	G	17: 22,948,163	R505G	probably benign	Het
Vmn2r75	A	C	7: 86,165,384	D300E	probably damaging	Het
Zfp318	T	A	17: 46,397,306		probably null	Het
Zfp318	T	C	17: 46,405,939	V999A	probably damaging	Het
Zfp324	A	T	7: 12,968,883	H58L	probably damaging	Het
Zfp707	A	G	15: 75,975,118	E339G	possibly 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
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
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
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
R8699:Map4k4	UTSW	1	39976750	missense	unknown
R8726:Map4k4	UTSW	1	40003982	missense	possibly damaging	0.95
R8907:Map4k4	UTSW	1	40019610	missense	probably damaging	0.97
R8956:Map4k4	UTSW	1	40000680	missense	probably benign	0.11
R8963:Map4k4	UTSW	1	40000580	missense	probably damaging	1.00
R9091:Map4k4	UTSW	1	40003763	missense	probably benign	0.02
R9234:Map4k4	UTSW	1	39990101	missense	unknown
R9270:Map4k4	UTSW	1	40003763	missense	probably benign	0.02
R9438:Map4k4	UTSW	1	40006792	missense	probably damaging	0.99
R9689:Map4k4	UTSW	1	40019562	missense	possibly damaging	0.95
R9771:Map4k4	UTSW	1	39986717	missense	unknown

Predicted Primers

PCR Primer
(F):5'- GATGGTCAGACTTGTTACGTCC -3'
(R):5'- GAAGCTGCTGTCCCTTTGTC -3'

Sequencing Primer
(F):5'- CCTTCTCCCGTGGTCATATTCAGAAG -3'
(R):5'- GCTGTCCCTTTGTCTTTGTTTC -3'

Posted On

2019-06-26