Mutagenetix > Incidental Mutation

Incidental Mutation 'R5297:Map4k4'

405448

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

042880-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5297 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

39900913-40026310 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 39962217 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Phenylalanine at position 55 (V55F)

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: V55F

SMART Domains

Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: V55F

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: V55F

SMART Domains

Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: V55F

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

probably damaging
Transcript: ENSMUST00000191761
AA Change: V55F

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000141332
Gene: ENSMUSG00000026074
AA Change: V55F

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: V55F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: V55F

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: V55F

SMART Domains

Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: V55F

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

probably damaging
Transcript: ENSMUST00000195259
AA Change: V55F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: V55F

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

probably damaging
Transcript: ENSMUST00000195636
AA Change: V55F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: V55F

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: V55F

SMART Domains

Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: V55F

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: 99.4%
3x: 98.7%
10x: 97.4%
20x: 95.6%

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: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acbd6	G	T	1: 155,587,458	A135S	probably benign	Het
Agbl4	A	G	4: 111,566,698	K307R	possibly damaging	Het
AI481877	A	G	4: 59,047,543	W1359R	probably benign	Het
Akna	T	C	4: 63,381,846	E653G	possibly damaging	Het
Arhgap26	T	C	18: 39,121,888	Y273H	probably damaging	Het
Atg14	G	A	14: 47,568,199	R70C	probably damaging	Het
Atp1a1	C	T	3: 101,591,127	V250M	possibly damaging	Het
Cacna1c	T	G	6: 118,742,361	D215A	probably damaging	Het
Cadps	T	A	14: 12,822,345	N132Y	probably damaging	Het
Casp6	T	C	3: 129,910,555	F97L	possibly damaging	Het
Ckap2l	T	C	2: 129,285,370	N296S	possibly damaging	Het
Col6a4	T	C	9: 106,074,867	K611E	probably benign	Het
Copa	A	G	1: 172,113,108	H696R	probably damaging	Het
Cyp2a4	T	A	7: 26,312,204	N283K	probably benign	Het
Dcc	C	T	18: 71,378,738	V869I	probably benign	Het
Efemp1	G	T	11: 28,867,868	G116C	probably damaging	Het
F830045P16Rik	T	C	2: 129,460,553	E373G	probably benign	Het
Fbxo9	T	C	9: 78,086,279	T318A	probably benign	Het
Gipr	A	G	7: 19,157,544	W403R	probably damaging	Het
Gm10093	A	G	17: 78,492,758	S393G	probably benign	Het
Gm12794	T	A	4: 101,941,151	D106E	possibly damaging	Het
Gm4787	G	C	12: 81,377,830	T518S	probably benign	Het
Golgb1	G	A	16: 36,875,616		probably benign	Het
Herc3	T	C	6: 58,856,641	L171P	probably damaging	Het
Il5ra	A	G	6: 106,738,134	I221T	probably benign	Het
Itgb2	A	G	10: 77,564,667	I705V	probably damaging	Het
Mast1	A	G	8: 84,913,318		probably null	Het
Mitf	G	T	6: 97,994,430	G186V	probably benign	Het
Mtpn	C	T	6: 35,512,290	D100N	probably benign	Het
Nrcam	T	C	12: 44,544,784	F204L	probably damaging	Het
Olfr1	AGCGGTCGTAGGC	AGC	11: 73,395,654		probably null	Het
Olfr1111	T	C	2: 87,150,449	I71V	probably benign	Het
Olfr1510	A	G	14: 52,410,218	L218P	probably damaging	Het
Olfr248	A	G	1: 174,391,200	M44V	probably benign	Het
Olfr381	A	T	11: 73,486,389	V145E	probably damaging	Het
Olfr446	T	C	6: 42,927,437	S69P	probably benign	Het
Olfr503	A	T	7: 108,545,404	N291I	probably damaging	Het
Pclo	A	T	5: 14,676,249		probably benign	Het
Pik3ca	T	A	3: 32,450,053	Y631N	probably damaging	Het
Ptk2b	T	C	14: 66,172,517	D462G	probably benign	Het
Rnf19a	A	G	15: 36,247,778	S427P	probably damaging	Het
Scn3a	T	A	2: 65,469,034	Y1376F	possibly damaging	Het
Spem1	A	G	11: 69,820,927	Y304H	probably damaging	Het
Stk38l	C	A	6: 146,775,655	Y450*	probably null	Het
Stx19	A	G	16: 62,821,974	E51G	probably damaging	Het
Ttc41	C	G	10: 86,776,579	Q1239E	probably benign	Het
Tuba3a	C	T	6: 125,281,340	R229H	probably damaging	Het
Utp18	A	T	11: 93,876,089	V264D	probably damaging	Het
V1rd19	T	C	7: 24,003,289	V60A	probably damaging	Het
Virma	T	G	4: 11,494,819	V40G	probably damaging	Het
Vmn1r160	C	T	7: 22,871,290	Q23*	probably null	Het
Vmn2r13	T	C	5: 109,191,939	I57V	probably benign	Het
Vmn2r26	T	A	6: 124,061,873	F802L	probably damaging	Het
Vmn2r61	A	G	7: 42,260,222	D57G	probably benign	Het
Vps13c	A	G	9: 67,878,131	N260S	probably damaging	Het
Xirp1	C	A	9: 120,019,602	A72S	probably damaging	Het
Zfp212	T	C	6: 47,929,077	V190A	probably benign	Het
Zfp703	C	T	8: 26,979,205	P299L	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
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
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
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'- CCGTTGTTCTATTATGAGCATGC -3'
(R):5'- TGGCCAAAGATGACATCACTCC -3'

Sequencing Primer
(F):5'- CTATTATGAGCATGCACTTAAAAGC -3'
(R):5'- AACTCAAGTCGCCTGGC -3'

Posted On

2016-07-22