Mutagenetix > Incidental Mutation

Incidental Mutation 'R1634:Map3k5'

172996

Institutional Source

Beutler Lab

Gene Symbol

Map3k5

Ensembl Gene

ENSMUSG00000071369

Gene Name

mitogen-activated protein kinase kinase kinase 5

Synonyms

ASK, ASK1, 7420452D20Rik, Mekk5

MMRRC Submission

039671-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1634 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

19934472-20142753 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 20136911 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 1259 (V1259A)

Ref Sequence

ENSEMBL: ENSMUSP00000112864 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000095806] [ENSMUST00000120259]

AlphaFold

O35099

Predicted Effect

possibly damaging
Transcript: ENSMUST00000095806
AA Change: V1267A

PolyPhen 2 Score 0.641 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000093485
Gene: ENSMUSG00000071369
AA Change: V1267A

Domain	Start	End	E-Value	Type
low complexity region	26	43	N/A	INTRINSIC
low complexity region	44	58	N/A	INTRINSIC
low complexity region	80	99	N/A	INTRINSIC
Pfam:DUF4071	172	552	2.1e-162	PFAM
S_TKc	687	945	8.08e-92	SMART
low complexity region	1195	1207	N/A	INTRINSIC
low complexity region	1225	1238	N/A	INTRINSIC
coiled coil region	1251	1292	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000120259
AA Change: V1259A

PolyPhen 2 Score 0.641 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000112864
Gene: ENSMUSG00000071369
AA Change: V1259A

Domain	Start	End	E-Value	Type
low complexity region	26	43	N/A	INTRINSIC
low complexity region	44	58	N/A	INTRINSIC
low complexity region	80	99	N/A	INTRINSIC
Pfam:DUF4071	172	544	1.7e-156	PFAM
S_TKc	679	937	8.08e-92	SMART
low complexity region	1187	1199	N/A	INTRINSIC
low complexity region	1217	1230	N/A	INTRINSIC
coiled coil region	1243	1284	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142726

Meta Mutation Damage Score

0.0590

Coding Region Coverage

1x: 99.0%
3x: 98.2%
10x: 95.7%
20x: 90.4%

Validation Efficiency

97% (67/69)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutant mice are overtly normal, however apoptosis abnormalities are evident in cultured cells and after induced heart damage. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam2	A	T	14: 66,057,731	F222I	probably damaging	Het
Adam34	A	T	8: 43,652,090	C173S	possibly damaging	Het
Ahi1	T	C	10: 20,965,693	V293A	probably damaging	Het
AI182371	A	T	2: 35,086,485	Y223N	probably damaging	Het
Armc4	A	G	18: 7,286,688	L181P	probably damaging	Het
Asmt	C	A	X: 170,675,829	F181L	probably damaging	Het
Axin1	T	A	17: 26,187,991	H519Q	probably damaging	Het
Cdc5l	A	T	17: 45,404,706	V660E	probably damaging	Het
Cep152	C	T	2: 125,583,889	R852H	probably benign	Het
Cpne4	T	C	9: 104,989,579	V230A	possibly damaging	Het
Cttnbp2	A	T	6: 18,408,657	N988K	probably benign	Het
D430041D05Rik	A	G	2: 104,221,211	I767T	probably damaging	Het
Dgki	A	G	6: 36,915,490	M851T	probably benign	Het
Dnah8	T	C	17: 30,713,098		probably null	Het
Dscaml1	A	G	9: 45,672,749	E504G	probably damaging	Het
Dzank1	G	A	2: 144,481,669	A618V	probably benign	Het
Fam189b	A	C	3: 89,188,094	Y511S	probably damaging	Het
Fat2	T	A	11: 55,267,684	S3403C	probably damaging	Het
Fat2	C	T	11: 55,284,719	V1723I	probably benign	Het
Flt1	A	T	5: 147,676,430	F334I	probably damaging	Het
Galnt12	G	T	4: 47,108,585		probably null	Het
Gzmc	T	C	14: 56,232,280	I188V	possibly damaging	Het
Herc1	T	C	9: 66,473,538	S3566P	possibly damaging	Het
Hoxb4	C	A	11: 96,320,273		probably benign	Het
Idh3b	C	T	2: 130,281,745	V141I	probably benign	Het
Kif24	A	G	4: 41,393,529	S1249P	probably benign	Het
Leo1	T	C	9: 75,466,260	Y656H	possibly damaging	Het
Map3k20	G	A	2: 72,410,177	W339*	probably null	Het
Masp2	A	G	4: 148,614,355	D631G	probably damaging	Het
Mink1	T	C	11: 70,608,880	S713P	probably benign	Het
Mpp7	A	T	18: 7,350,984	V571E	possibly damaging	Het
Nell1	A	G	7: 50,848,558	D574G	possibly damaging	Het
Obscn	T	C	11: 59,076,896	Y392C	probably damaging	Het
Olfml2a	A	T	2: 38,960,219	Y649F	probably benign	Het
Olfr1295	T	C	2: 111,565,346	M33V	probably benign	Het
Olfr161	A	G	16: 3,593,209	D271G	probably benign	Het
Prkcg	A	G	7: 3,323,470	D484G	probably damaging	Het
Rab27a	T	C	9: 73,075,569		probably null	Het
Rapgef6	TG	TGG	11: 54,546,397		probably null	Het
Rgl1	C	T	1: 152,524,772	R624H	probably damaging	Het
Ric8b	G	A	10: 84,970,748	G159D	probably damaging	Het
Sbno2	C	A	10: 80,060,634	A880S	possibly damaging	Het
Scn9a	A	G	2: 66,488,017	S1477P	probably damaging	Het
Sec22a	T	C	16: 35,318,873		probably benign	Het
Snx14	T	C	9: 88,385,739	I714M	probably benign	Het
Snx14	T	C	9: 88,407,490		probably benign	Het
Sphk2	T	A	7: 45,711,540	T347S	probably benign	Het
Spns1	C	T	7: 126,371,171		probably benign	Het
Susd2	A	G	10: 75,637,555	V675A	probably benign	Het
Sytl2	A	T	7: 90,395,182	D566V	probably damaging	Het
Tcf25	T	A	8: 123,397,091	I464N	possibly damaging	Het
Tex261	A	T	6: 83,775,022	I49N	possibly damaging	Het
Tjp1	A	G	7: 65,302,952	F1545L	possibly damaging	Het
Tmem176b	A	G	6: 48,834,566	S216P	probably damaging	Het
Topaz1	C	T	9: 122,780,675		probably benign	Het
Tra2a	C	T	6: 49,250,957		probably benign	Het
Ttn	A	G	2: 76,722,782	F22794S	possibly damaging	Het
Uox	G	A	3: 146,612,383	W93*	probably null	Het
Zan	A	T	5: 137,412,790		probably benign	Het
Zfp106	G	A	2: 120,533,677	R750*	probably null	Het
Zfp638	A	T	6: 83,979,912		probably null	Het

Other mutations in Map3k5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00569:Map3k5	APN	10	19935044	missense	possibly damaging	0.73
IGL00978:Map3k5	APN	10	20141567	missense	probably damaging	1.00
IGL01470:Map3k5	APN	10	20118187	missense	possibly damaging	0.89
IGL01992:Map3k5	APN	10	20029133	nonsense	probably null
IGL02479:Map3k5	APN	10	20056484	missense	probably damaging	1.00
IGL02728:Map3k5	APN	10	20118292	missense	possibly damaging	0.71
IGL02812:Map3k5	APN	10	20025036	missense	probably damaging	1.00
IGL03104:Map3k5	APN	10	20132055	missense	probably benign
P0033:Map3k5	UTSW	10	20132213	splice site	probably benign
PIT4434001:Map3k5	UTSW	10	20026257	missense	probably damaging	0.98
R0284:Map3k5	UTSW	10	20000613	missense	probably damaging	0.99
R1103:Map3k5	UTSW	10	20023676	missense	probably benign	0.00
R1172:Map3k5	UTSW	10	20056648	intron	probably benign
R1250:Map3k5	UTSW	10	20110775	missense	possibly damaging	0.73
R1493:Map3k5	UTSW	10	20029113	missense	probably damaging	1.00
R1693:Map3k5	UTSW	10	20104242	missense	probably damaging	1.00
R1713:Map3k5	UTSW	10	20110847	missense	possibly damaging	0.79
R1832:Map3k5	UTSW	10	20099560	missense	probably damaging	1.00
R1844:Map3k5	UTSW	10	20104163	missense	probably benign	0.33
R1869:Map3k5	UTSW	10	20132109	nonsense	probably null
R2156:Map3k5	UTSW	10	20024937	missense	probably damaging	1.00
R2214:Map3k5	UTSW	10	20026289	critical splice donor site	probably null
R2221:Map3k5	UTSW	10	20067920	missense	possibly damaging	0.96
R2223:Map3k5	UTSW	10	20067920	missense	possibly damaging	0.96
R2249:Map3k5	UTSW	10	20127697	missense	probably damaging	0.99
R2418:Map3k5	UTSW	10	20110857	missense	probably benign	0.02
R2513:Map3k5	UTSW	10	20094455	missense	possibly damaging	0.92
R3014:Map3k5	UTSW	10	20094429	missense	probably damaging	1.00
R3770:Map3k5	UTSW	10	20025019	missense	probably damaging	0.99
R3814:Map3k5	UTSW	10	20026190	missense	probably damaging	0.99
R3814:Map3k5	UTSW	10	20140680	missense	probably damaging	0.99
R4706:Map3k5	UTSW	10	20058938	missense	probably damaging	1.00
R4749:Map3k5	UTSW	10	20132052	missense	probably benign	0.42
R4903:Map3k5	UTSW	10	20118489	missense	probably null	1.00
R4958:Map3k5	UTSW	10	20023789	missense	possibly damaging	0.79
R5065:Map3k5	UTSW	10	20082467	missense	probably damaging	1.00
R5210:Map3k5	UTSW	10	20024901	missense	possibly damaging	0.82
R5245:Map3k5	UTSW	10	20140691	missense	probably benign	0.00
R5304:Map3k5	UTSW	10	20108238	missense	probably benign	0.13
R5428:Map3k5	UTSW	10	20023653	missense	possibly damaging	0.93
R5566:Map3k5	UTSW	10	20110719	missense	probably damaging	1.00
R5914:Map3k5	UTSW	10	20104255	missense	probably benign	0.24
R6155:Map3k5	UTSW	10	20118441	missense	probably benign	0.01
R6161:Map3k5	UTSW	10	20000575	missense	probably damaging	0.98
R6191:Map3k5	UTSW	10	20023669	missense	probably damaging	0.99
R6251:Map3k5	UTSW	10	20138260	splice site	probably null
R6800:Map3k5	UTSW	10	20141580	makesense	probably null
R7304:Map3k5	UTSW	10	20099555	missense	probably damaging	1.00
R7722:Map3k5	UTSW	10	20132145	missense	probably benign	0.04
R8058:Map3k5	UTSW	10	20132114	missense	probably damaging	0.99
R8207:Map3k5	UTSW	10	20110866	frame shift	probably null
R8827:Map3k5	UTSW	10	20026257	missense	probably damaging	0.98
R8977:Map3k5	UTSW	10	20079254	missense	possibly damaging	0.88
R9490:Map3k5	UTSW	10	20132051	missense	probably benign
R9570:Map3k5	UTSW	10	20000568	missense	probably benign	0.02
R9784:Map3k5	UTSW	10	19935066	missense	probably damaging	1.00
RF024:Map3k5	UTSW	10	20100172	missense	probably damaging	1.00
X0017:Map3k5	UTSW	10	20118434	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- CAGACACATGCCAGACAGTGTGAG -3'
(R):5'- GCTGCCCATGAAGCTCTAACCC -3'

Sequencing Primer
(F):5'- AGGTAGCCTGACCTAAGTTAGTCC -3'
(R):5'- TGAAGCTCTAACCCACAGC -3'

Posted On

2014-04-24