Mutagenetix > Incidental Mutation

Incidental Mutation 'R6232:Map3k12'

504708

Institutional Source

Beutler Lab

Gene Symbol

Map3k12

Ensembl Gene

ENSMUSG00000023050

Gene Name

mitogen-activated protein kinase kinase kinase 12

Synonyms

MUK, DLK, Zpk

MMRRC Submission

044360-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6232 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

102406079-102425311 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 102412081 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 328 (S328P)

Ref Sequence

ENSEMBL: ENSMUSP00000127629 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000023812] [ENSMUST00000077037] [ENSMUST00000078404] [ENSMUST00000096145] [ENSMUST00000108838] [ENSMUST00000165174] [ENSMUST00000169377] [ENSMUST00000171565] [ENSMUST00000169367] [ENSMUST00000229854] [ENSMUST00000229618] [ENSMUST00000169162]

AlphaFold

Q60700

Predicted Effect

probably damaging
Transcript: ENSMUST00000023812
AA Change: S328P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000023812
Gene: ENSMUSG00000023050
AA Change: S328P

Domain	Start	End	E-Value	Type
low complexity region	54	75	N/A	INTRINSIC
Pfam:Pkinase	158	397	3.3e-59	PFAM
Pfam:Pkinase_Tyr	159	397	2.7e-62	PFAM
coiled coil region	447	501	N/A	INTRINSIC
low complexity region	559	577	N/A	INTRINSIC
low complexity region	599	617	N/A	INTRINSIC
low complexity region	640	663	N/A	INTRINSIC
low complexity region	664	678	N/A	INTRINSIC
low complexity region	691	727	N/A	INTRINSIC
low complexity region	751	764	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000077037

SMART Domains

Protein: ENSMUSP00000076294
Gene: ENSMUSG00000056851

Domain	Start	End	E-Value	Type
KH	12	80	5.96e-15	SMART
KH	96	167	2.48e-12	SMART
KH	283	353	5.19e-15	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000078404

SMART Domains

Protein: ENSMUSP00000077509
Gene: ENSMUSG00000056851

Domain	Start	End	E-Value	Type
KH	12	80	5.96e-15	SMART
KH	96	167	2.48e-12	SMART
KH	270	340	5.19e-15	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000096145

SMART Domains

Protein: ENSMUSP00000093859
Gene: ENSMUSG00000071586

Domain	Start	End	E-Value	Type
low complexity region	29	37	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000108838

SMART Domains

Protein: ENSMUSP00000104466
Gene: ENSMUSG00000056851

Domain	Start	End	E-Value	Type
KH	12	80	5.96e-15	SMART
KH	96	167	2.48e-12	SMART
KH	252	322	5.19e-15	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000164343

Predicted Effect

probably benign
Transcript: ENSMUST00000165174

Predicted Effect

probably damaging
Transcript: ENSMUST00000169377
AA Change: S328P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000133209
Gene: ENSMUSG00000023050
AA Change: S328P

Domain	Start	End	E-Value	Type
low complexity region	54	75	N/A	INTRINSIC
Pfam:Pkinase	159	397	1.2e-58	PFAM
Pfam:Pkinase_Tyr	160	397	3.7e-62	PFAM
coiled coil region	447	501	N/A	INTRINSIC
low complexity region	559	577	N/A	INTRINSIC
low complexity region	599	617	N/A	INTRINSIC
low complexity region	640	663	N/A	INTRINSIC
low complexity region	664	678	N/A	INTRINSIC
low complexity region	691	727	N/A	INTRINSIC
low complexity region	751	764	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000171565
AA Change: S328P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000127629
Gene: ENSMUSG00000023050
AA Change: S328P

Domain	Start	End	E-Value	Type
low complexity region	54	75	N/A	INTRINSIC
Pfam:Pkinase	158	397	3.3e-59	PFAM
Pfam:Pkinase_Tyr	159	397	2.7e-62	PFAM
coiled coil region	447	501	N/A	INTRINSIC
low complexity region	559	577	N/A	INTRINSIC
low complexity region	599	617	N/A	INTRINSIC
low complexity region	640	663	N/A	INTRINSIC
low complexity region	664	678	N/A	INTRINSIC
low complexity region	691	727	N/A	INTRINSIC
low complexity region	751	764	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000169367

Predicted Effect

probably benign
Transcript: ENSMUST00000229854

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000229822

Predicted Effect

probably benign
Transcript: ENSMUST00000229618

Predicted Effect

probably benign
Transcript: ENSMUST00000169162

Meta Mutation Damage Score

0.9694

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.5%
20x: 95.7%

Validation Efficiency

94% (64/68)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the serine/threonine protein kinase family. This kinase contains a leucine-zipper domain and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulated by membrane depolarization via calcineurin. This kinase forms heterodimers with leucine zipper containing transcription factors, such as cAMP responsive element binding protein (CREB) and MYC, and thus may play a regulatory role in PKA or retinoic acid induced neuronal differentiation. Alternatively spliced transcript variants encoding different proteins have been described.[provided by RefSeq, Jul 2010]
PHENOTYPE: Mice homozygous for a gene-trapped allele lack the brain anterior commissure. Mice homozygous for a knock-out allele exhibit postnatal lethality and abnormal axon growth and radial migration of neocortical pyramidal neurons. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsl5	T	C	19: 55,268,933 (GRCm39)	V198A	possibly damaging	Het
Adam34l	T	G	8: 44,078,949 (GRCm39)	N425T	probably benign	Het
Adgra2	A	T	8: 27,609,193 (GRCm39)	M805L	probably benign	Het
Arhgap39	T	C	15: 76,620,712 (GRCm39)	S630G	probably damaging	Het
Bcl3	T	A	7: 19,546,409 (GRCm39)	N142I	probably damaging	Het
Cfap210	C	T	2: 69,602,398 (GRCm39)	E338K	possibly damaging	Het
Chuk	A	T	19: 44,085,431 (GRCm39)	D238E	probably benign	Het
Cnga4	T	G	7: 105,056,906 (GRCm39)	Y336*	probably null	Het
Cyp2j8	A	T	4: 96,395,427 (GRCm39)	L66Q	possibly damaging	Het
Dnase1l1	C	T	X: 73,320,644 (GRCm39)		probably null	Homo
Dst	T	A	1: 34,227,253 (GRCm39)	D1290E	probably damaging	Het
Dysf	T	C	6: 84,075,235 (GRCm39)	I583T	probably benign	Het
Eif1ad13	A	T	12: 87,762,351 (GRCm39)	R24*	probably null	Het
Fbxl2	T	A	9: 113,815,516 (GRCm39)	D249V	probably damaging	Het
Fbxo30	A	T	10: 11,165,602 (GRCm39)	Y108F	possibly damaging	Het
Fibin	G	T	2: 110,193,041 (GRCm39)	H34N	probably damaging	Het
Gabrr1	A	G	4: 33,161,632 (GRCm39)	I319V	probably benign	Het
Gfm1	G	T	3: 67,375,215 (GRCm39)	L559F	possibly damaging	Het
Gm5134	T	A	10: 75,821,859 (GRCm39)	L231Q	possibly damaging	Het
Grm5	A	G	7: 87,251,638 (GRCm39)		probably benign	Het
Hbs1l	T	A	10: 21,183,657 (GRCm39)		probably null	Het
Hsf5	C	G	11: 87,508,120 (GRCm39)	T8S	probably benign	Het
Hspa4	C	T	11: 53,153,766 (GRCm39)	E702K	probably benign	Het
Inpp4b	A	G	8: 82,678,813 (GRCm39)	Q281R	probably damaging	Het
Krt40	G	A	11: 99,433,920 (GRCm39)	A22V	possibly damaging	Het
Ldlrap1	C	T	4: 134,486,345 (GRCm39)	R38Q	possibly damaging	Het
Lepr	A	G	4: 101,671,588 (GRCm39)		probably null	Het
Mrpl2	T	C	17: 46,958,356 (GRCm39)	V46A	probably benign	Het
Muc16	A	T	9: 18,568,294 (GRCm39)	N1408K	unknown	Het
Myh7	T	A	14: 55,226,753 (GRCm39)	Q366L	probably benign	Het
Nbeal2	A	G	9: 110,467,802 (GRCm39)	V462A	probably damaging	Het
Nradd	G	T	9: 110,450,655 (GRCm39)	T174N	probably damaging	Het
Nup155	T	C	15: 8,138,963 (GRCm39)	S12P	probably benign	Het
Obscn	C	A	11: 58,943,337 (GRCm39)	E4832*	probably null	Het
Opn3	G	A	1: 175,490,669 (GRCm39)	R331W	probably damaging	Het
Or2ag15	A	T	7: 106,340,761 (GRCm39)	C127S	probably damaging	Het
Or2w3	T	A	11: 58,556,757 (GRCm39)	V124E	possibly damaging	Het
Or4a66	G	T	2: 88,531,161 (GRCm39)	H171N	probably benign	Het
Or52ae9	T	A	7: 103,389,661 (GRCm39)	H262L	probably damaging	Het
Or5b120	G	A	19: 13,480,427 (GRCm39)	C240Y	probably damaging	Het
Or6b2	T	C	1: 92,408,305 (GRCm39)	I13V	probably benign	Het
Phip	A	G	9: 82,785,234 (GRCm39)	V827A	probably benign	Het
Phldb1	G	A	9: 44,607,414 (GRCm39)	R1264W	probably damaging	Het
Pibf1	T	G	14: 99,424,014 (GRCm39)	I529S	probably benign	Het
Pkp1	T	A	1: 135,814,599 (GRCm39)	I241F	probably benign	Het
Pla2g4f	G	T	2: 120,132,702 (GRCm39)	D711E	possibly damaging	Het
Pold1	A	G	7: 44,190,266 (GRCm39)		probably null	Het
Pold2	T	C	11: 5,823,691 (GRCm39)	S287G	probably benign	Het
Prg4	T	C	1: 150,331,567 (GRCm39)		probably benign	Het
Prl8a1	T	C	13: 27,759,557 (GRCm39)	E160G	possibly damaging	Het
Rfc4	C	T	16: 22,932,840 (GRCm39)		probably benign	Het
Robo3	T	G	9: 37,332,225 (GRCm39)	Y891S	probably damaging	Het
Rsf1	ATGGCG	ATGGCGACGGTGGCG	7: 97,229,111 (GRCm39)		probably benign	Homo
Rsph14	G	A	10: 74,797,520 (GRCm39)	R156W	probably benign	Het
Sec61a1	T	C	6: 88,482,150 (GRCm39)	Y457C	probably benign	Het
Sec63	T	A	10: 42,704,861 (GRCm39)		probably null	Het
Spen	T	C	4: 141,244,333 (GRCm39)	E234G	unknown	Het
Sphkap	T	A	1: 83,258,200 (GRCm39)	E181V	probably damaging	Het
Stau2	C	T	1: 16,445,035 (GRCm39)	A298T	probably benign	Het
Tbc1d2	C	T	4: 46,629,912 (GRCm39)	G252R	probably benign	Het
Tbc1d23	T	C	16: 56,990,796 (GRCm39)	I661V	probably benign	Het
Thoc6	A	C	17: 23,889,295 (GRCm39)		probably null	Het
Trpv1	T	A	11: 73,141,636 (GRCm39)	M553K	possibly damaging	Het
Ttn	T	C	2: 76,641,579 (GRCm39)	I11760V	probably benign	Het
Vmn1r61	G	A	7: 5,613,850 (GRCm39)	H155Y	probably damaging	Het
Vmn2r41	A	G	7: 8,153,214 (GRCm39)		probably null	Het
Vmn2r74	A	G	7: 85,607,498 (GRCm39)	I75T	possibly damaging	Het
Wwp2	C	A	8: 108,232,977 (GRCm39)	T205K	probably benign	Het
Zfp1003	A	T	2: 177,546,195 (GRCm39)	T40S	probably benign	Het
Zfp747	C	T	7: 126,973,306 (GRCm39)	G288D	probably damaging	Het
Zfp871	CCACAC	CC	17: 32,994,494 (GRCm39)		probably null	Het
Zfp953	G	A	13: 67,491,161 (GRCm39)	L264F	possibly damaging	Het

Other mutations in Map3k12

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01615:Map3k12	APN	15	102,412,186 (GRCm39)	missense	probably damaging	1.00
IGL01713:Map3k12	APN	15	102,410,756 (GRCm39)	missense	probably damaging	1.00
IGL01720:Map3k12	APN	15	102,410,621 (GRCm39)	unclassified	probably benign
IGL02262:Map3k12	APN	15	102,410,510 (GRCm39)	missense	probably damaging	1.00
IGL02670:Map3k12	APN	15	102,411,981 (GRCm39)	missense	probably benign	0.09
IGL03004:Map3k12	APN	15	102,412,631 (GRCm39)	missense	possibly damaging	0.96
IGL03369:Map3k12	APN	15	102,410,514 (GRCm39)	missense	possibly damaging	0.47
react	UTSW	15	102,413,837 (GRCm39)	missense	probably damaging	1.00
R0894:Map3k12	UTSW	15	102,410,613 (GRCm39)	missense	probably damaging	1.00
R0918:Map3k12	UTSW	15	102,412,287 (GRCm39)	missense	probably damaging	0.99
R1547:Map3k12	UTSW	15	102,412,287 (GRCm39)	missense	probably damaging	1.00
R1844:Map3k12	UTSW	15	102,411,970 (GRCm39)	missense	probably damaging	1.00
R1880:Map3k12	UTSW	15	102,410,499 (GRCm39)	critical splice donor site	probably null
R2292:Map3k12	UTSW	15	102,408,574 (GRCm39)	missense	probably damaging	0.96
R4397:Map3k12	UTSW	15	102,409,694 (GRCm39)	missense	probably benign	0.44
R4406:Map3k12	UTSW	15	102,413,837 (GRCm39)	missense	probably damaging	1.00
R4407:Map3k12	UTSW	15	102,413,837 (GRCm39)	missense	probably damaging	1.00
R4408:Map3k12	UTSW	15	102,413,837 (GRCm39)	missense	probably damaging	1.00
R4731:Map3k12	UTSW	15	102,409,717 (GRCm39)	missense	probably benign	0.28
R5074:Map3k12	UTSW	15	102,410,267 (GRCm39)	critical splice donor site	probably null
R5605:Map3k12	UTSW	15	102,412,300 (GRCm39)	missense	probably benign	0.17
R5848:Map3k12	UTSW	15	102,412,670 (GRCm39)	missense	possibly damaging	0.66
R6901:Map3k12	UTSW	15	102,409,065 (GRCm39)	missense	possibly damaging	0.65
R6901:Map3k12	UTSW	15	102,409,064 (GRCm39)	missense	possibly damaging	0.95
R6946:Map3k12	UTSW	15	102,413,569 (GRCm39)	missense	possibly damaging	0.89
R7291:Map3k12	UTSW	15	102,410,601 (GRCm39)	missense	probably damaging	1.00
R7874:Map3k12	UTSW	15	102,409,077 (GRCm39)	missense	possibly damaging	0.91
R8331:Map3k12	UTSW	15	102,410,766 (GRCm39)	nonsense	probably null
R8460:Map3k12	UTSW	15	102,410,032 (GRCm39)	missense	probably damaging	1.00
R8784:Map3k12	UTSW	15	102,413,797 (GRCm39)	missense	possibly damaging	0.51

Predicted Primers

PCR Primer
(F):5'- ACATCTGAGCCTAGATGTCTTG -3'
(R):5'- AGCACCAAGATGTCCTTTGC -3'

Sequencing Primer
(F):5'- CATCTGAGCCTAGATGTCTTGAGTTC -3'
(R):5'- CCTTTGCAGGAACAGTAGCC -3'

Posted On

2018-02-28