Mutagenetix > Incidental Mutation

Incidental Mutation 'R4760:Mlkl'

356813

Institutional Source

Beutler Lab

Gene Symbol

Mlkl

Ensembl Gene

ENSMUSG00000012519

Gene Name

mixed lineage kinase domain-like

Synonyms

9130019I15Rik

MMRRC Submission

041974-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.075) question?

Stock #

R4760 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

112038429-112064809 bp(-) (GRCm39)

Type of Mutation

critical splice donor site (1 bp from exon)

DNA Base Change (assembly)

C to G at 112046348 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000113718 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056157] [ENSMUST00000120432]

AlphaFold

Q9D2Y4

Predicted Effect

probably null
Transcript: ENSMUST00000056157

SMART Domains

Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519

Domain	Start	End	E-Value	Type
low complexity region	109	115	N/A	INTRINSIC
Pfam:Pkinase_Tyr	195	448	2.7e-41	PFAM
Pfam:Pkinase	200	450	2.1e-30	PFAM
Pfam:Kinase-like	270	438	1.6e-7	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000120432

SMART Domains

Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519

Domain	Start	End	E-Value	Type
low complexity region	109	115	N/A	INTRINSIC
Pfam:Pkinase_Tyr	195	453	3.3e-42	PFAM
Pfam:Pkinase	196	453	1.4e-33	PFAM
Pfam:Kinase-like	270	438	8.9e-8	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135710

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000212417

Meta Mutation Damage Score

0.9487

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.4%

Validation Efficiency

98% (90/92)

MGI Phenotype

FUNCTION: This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to lack protein kinase activity. This protein plays a critical role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process, via interaction with receptor-interacting protein 3 (Rip3), which is a key signaling molecule in necroptosis pathway. Knockout of this gene in mice showed that it is essential for necroptosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit imapired macrophage and mouse embryonic fibroblast necroptosis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A530053G22Rik	A	G	6: 60,379,086 (GRCm39)		noncoding transcript	Het
Abcc2	A	T	19: 43,798,920 (GRCm39)	Y512F	probably benign	Het
Adgrb1	T	A	15: 74,443,312 (GRCm39)	I51N	probably damaging	Het
Adhfe1	A	G	1: 9,633,748 (GRCm39)	Y332C	probably damaging	Het
Ambn	C	T	5: 88,615,566 (GRCm39)	L317F	probably damaging	Het
Amn1	T	C	6: 149,086,611 (GRCm39)	Y17C	probably benign	Het
Apoa5	T	C	9: 46,181,593 (GRCm39)	V223A	probably damaging	Het
Best3	A	T	10: 116,860,699 (GRCm39)	H653L	probably benign	Het
Btnl2	C	A	17: 34,582,169 (GRCm39)	S245Y	probably damaging	Het
Camk1d	A	G	2: 5,366,867 (GRCm39)	L116P	probably damaging	Het
Catsperg2	T	A	7: 29,405,060 (GRCm39)	D698V	probably damaging	Het
Cd33	T	C	7: 43,178,919 (GRCm39)	T307A	probably benign	Het
Cdk8	C	T	5: 146,229,476 (GRCm39)	S230L	probably benign	Het
Cfap69	C	T	5: 5,696,939 (GRCm39)	C119Y	probably damaging	Het
Chat	T	C	14: 32,175,694 (GRCm39)	N122S	probably benign	Het
Col20a1	A	T	2: 180,626,196 (GRCm39)		probably benign	Het
Cyp2j9	A	T	4: 96,457,028 (GRCm39)	L481Q	probably damaging	Het
Dab1	A	C	4: 104,589,342 (GRCm39)	S550R	probably damaging	Het
Dlgap2	A	C	8: 14,823,380 (GRCm39)	Q533P	probably damaging	Het
Eif4g3	A	T	4: 137,811,629 (GRCm39)	Q31L	possibly damaging	Het
Ets2	G	A	16: 95,520,087 (GRCm39)	V438M	probably damaging	Het
Eva1c	G	A	16: 90,701,138 (GRCm39)	D258N	probably benign	Het
Fastkd2	A	G	1: 63,785,045 (GRCm39)	H477R	probably benign	Het
Fga	T	G	3: 82,938,821 (GRCm39)	S399A	probably benign	Het
Fmo4	T	A	1: 162,637,396 (GRCm39)	E32V	probably damaging	Het
Gm7204	T	A	16: 48,039,051 (GRCm39)		noncoding transcript	Het
Gpi-ps	G	A	8: 5,690,473 (GRCm39)		noncoding transcript	Het
Hhipl1	A	G	12: 108,286,336 (GRCm39)	I548V	probably damaging	Het
Hsfy2	T	C	1: 56,676,349 (GRCm39)	T63A	probably benign	Het
Igf2r	A	G	17: 12,922,352 (GRCm39)	V1254A	possibly damaging	Het
Ighv8-4	A	T	12: 114,987,667 (GRCm39)	D110E	probably damaging	Het
Igkv14-130	T	C	6: 67,768,446 (GRCm39)	S101P	probably benign	Het
Igkv9-120	G	T	6: 68,027,351 (GRCm39)	R88S	possibly damaging	Het
Ipo5	T	C	14: 121,179,054 (GRCm39)	V779A	probably benign	Het
Itpr1	C	T	6: 108,326,593 (GRCm39)	T105I	probably benign	Het
Kalrn	T	C	16: 34,018,857 (GRCm39)	M670V	probably damaging	Het
Kdm8	T	A	7: 125,054,431 (GRCm39)		probably null	Het
Kics2	T	C	10: 121,575,912 (GRCm39)	V11A	probably damaging	Het
L3hypdh	T	C	12: 72,124,016 (GRCm39)	I281V	probably benign	Het
Lins1	T	G	7: 66,364,435 (GRCm39)		probably benign	Het
Map4k5	T	A	12: 69,871,372 (GRCm39)	I517L	possibly damaging	Het
Marchf2	G	T	17: 33,928,890 (GRCm39)	T2K	probably damaging	Het
Mllt1	A	G	17: 57,209,630 (GRCm39)	M160T	probably benign	Het
Mmp15	G	A	8: 96,094,824 (GRCm39)	A233T	possibly damaging	Het
Moxd2	C	A	6: 40,868,537 (GRCm39)	T23N	probably benign	Het
Nop53	C	A	7: 15,676,812 (GRCm39)	K100N	probably benign	Het
Nrg1	C	A	8: 32,408,228 (GRCm39)	E2*	probably null	Het
Or52u1	T	A	7: 104,237,696 (GRCm39)	H228Q	probably benign	Het
Pank4	A	G	4: 155,059,091 (GRCm39)	D408G	possibly damaging	Het
Pcdhb10	T	C	18: 37,544,995 (GRCm39)	W24R	probably benign	Het
Pcm1	C	T	8: 41,740,775 (GRCm39)	T968I	probably damaging	Het
Pkib	G	T	10: 57,584,246 (GRCm39)	M19I	probably benign	Het
Ppy	A	G	11: 101,991,345 (GRCm39)		probably null	Het
Pramel21	G	A	4: 143,343,801 (GRCm39)	R367K	probably benign	Het
Prdx3	A	C	19: 60,861,621 (GRCm39)	C39W	possibly damaging	Het
Qrfpr	T	G	3: 36,276,073 (GRCm39)	N106H	probably benign	Het
Rai14	G	A	15: 10,575,776 (GRCm39)	T394M	possibly damaging	Het
Ralgapa2	A	T	2: 146,188,669 (GRCm39)	L1371Q	probably benign	Het
Rbm12	A	G	2: 155,939,048 (GRCm39)	L408P	probably damaging	Het
Rdx	T	C	9: 51,977,174 (GRCm39)	I141T	probably benign	Het
Reep1	T	A	6: 71,684,985 (GRCm39)	V11E	possibly damaging	Het
Relch	T	A	1: 105,649,030 (GRCm39)	M723K	probably benign	Het
Sall4	A	G	2: 168,592,347 (GRCm39)	S936P	probably damaging	Het
Serac1	A	G	17: 6,102,065 (GRCm39)	M403T	possibly damaging	Het
Shroom3	G	T	5: 93,090,945 (GRCm39)	V1151F	probably damaging	Het
Slc35g2	T	G	9: 100,435,549 (GRCm39)	I41L	probably benign	Het
Slc39a12	G	A	2: 14,405,134 (GRCm39)	S242N	probably benign	Het
Slc9a2	T	A	1: 40,801,076 (GRCm39)	D535E	probably damaging	Het
Spata31d1a	G	T	13: 59,849,459 (GRCm39)	P890T	probably damaging	Het
Sync	A	G	4: 129,187,232 (GRCm39)	Q88R	probably benign	Het
Tdrp	A	G	8: 14,024,527 (GRCm39)		probably benign	Het
Tg	G	T	15: 66,565,168 (GRCm39)	C1170F	probably damaging	Het
Tnks	A	T	8: 35,318,937 (GRCm39)	D781E	probably benign	Het
Tnp2	T	A	16: 10,606,207 (GRCm39)	T87S	possibly damaging	Het
Tpp2	T	C	1: 44,010,875 (GRCm39)	V554A	probably benign	Het
Traf3ip2	T	C	10: 39,521,735 (GRCm39)	I431T	probably damaging	Het
Trav9d-4	A	T	14: 53,221,258 (GRCm39)	H84L	probably damaging	Het
Vmn2r42	T	A	7: 8,187,276 (GRCm39)	Y782F	probably damaging	Het
Vwf	T	C	6: 125,547,567 (GRCm39)	S231P	probably damaging	Het
Wdr83os	A	G	8: 85,808,496 (GRCm39)	S83G	probably damaging	Het
Wdr91	T	A	6: 34,885,234 (GRCm39)	Q109L	probably damaging	Het
Znrf4	A	G	17: 56,818,864 (GRCm39)	C148R	possibly damaging	Het

Other mutations in Mlkl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00089:Mlkl	APN	8	112,046,060 (GRCm39)	nonsense	probably null
IGL01376:Mlkl	APN	8	112,046,379 (GRCm39)	missense	probably damaging	1.00
IGL02801:Mlkl	APN	8	112,043,064 (GRCm39)	missense	probably benign	0.18
IGL02965:Mlkl	APN	8	112,058,469 (GRCm39)	missense	probably benign	0.31
IGL03121:Mlkl	APN	8	112,041,612 (GRCm39)	missense	probably damaging	1.00
Ghoulish	UTSW	8	112,049,380 (GRCm39)	missense	probably damaging	1.00
mecro	UTSW	8	112,046,348 (GRCm39)	critical splice donor site	probably null
necro	UTSW	8	112,038,732 (GRCm39)	intron	probably benign
secro	UTSW	8	112,042,199 (GRCm39)	intron	probably benign
R0133:Mlkl	UTSW	8	112,054,580 (GRCm39)	missense	probably damaging	1.00
R0230:Mlkl	UTSW	8	112,041,694 (GRCm39)	missense	probably benign	0.07
R0387:Mlkl	UTSW	8	112,059,982 (GRCm39)	missense	probably damaging	1.00
R0497:Mlkl	UTSW	8	112,054,505 (GRCm39)	missense	probably damaging	1.00
R0735:Mlkl	UTSW	8	112,054,433 (GRCm39)	unclassified	probably benign
R1733:Mlkl	UTSW	8	112,049,380 (GRCm39)	missense	probably damaging	1.00
R1761:Mlkl	UTSW	8	112,060,355 (GRCm39)	missense	possibly damaging	0.81
R1911:Mlkl	UTSW	8	112,038,732 (GRCm39)	intron	probably benign
R2057:Mlkl	UTSW	8	112,060,242 (GRCm39)	missense	probably benign	0.07
R2921:Mlkl	UTSW	8	112,043,079 (GRCm39)	missense	probably benign	0.02
R3745:Mlkl	UTSW	8	112,042,199 (GRCm39)	intron	probably benign
R5377:Mlkl	UTSW	8	112,054,569 (GRCm39)	missense	probably benign	0.23
R7052:Mlkl	UTSW	8	112,046,074 (GRCm39)	missense	possibly damaging	0.65
R7155:Mlkl	UTSW	8	112,046,035 (GRCm39)	missense	probably damaging	1.00
R7459:Mlkl	UTSW	8	112,060,162 (GRCm39)	missense	probably benign	0.36
R7728:Mlkl	UTSW	8	112,060,251 (GRCm39)	missense	probably damaging	1.00
R8036:Mlkl	UTSW	8	112,060,086 (GRCm39)	missense	probably damaging	1.00
R8064:Mlkl	UTSW	8	112,038,700 (GRCm39)	missense	probably benign	0.38
R9088:Mlkl	UTSW	8	112,049,365 (GRCm39)	missense
R9152:Mlkl	UTSW	8	112,046,403 (GRCm39)	missense	probably damaging	1.00
R9275:Mlkl	UTSW	8	112,043,055 (GRCm39)	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- ATGGGATCGCGAGACATTCTAG -3'
(R):5'- TGGGGCTGGATCTTTACAATACC -3'

Sequencing Primer
(F):5'- TGGCGATCTGTGGGCAAC -3'
(R):5'- GCTGGATCTTTACAATACCTTGCTTC -3'

Posted On

2015-11-11