Mutagenetix > Incidental Mutation

Incidental Mutation 'R7052:Mlkl'

547660

Institutional Source

Beutler Lab

Gene Symbol

Mlkl

Ensembl Gene

ENSMUSG00000012519

Gene Name

mixed lineage kinase domain-like

Synonyms

9130019I15Rik

MMRRC Submission

Accession Numbers

Is this an essential gene?

Probably non essential (E-score: 0.086) question?

Stock #

R7052 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

111311797-111338177 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 111319442 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Leucine at position 312 (S312L)

Ref Sequence

ENSEMBL: ENSMUSP00000055521 (fasta)

Gene Model

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

AlphaFold

Q9D2Y4

PDB Structure

Structure of MLKL [X-RAY DIFFRACTION]
Crystal structure of the mouse MLKL kinase-like domain [X-RAY DIFFRACTION]
Crystal structure of the mouse RIP3-MLKL complex [X-RAY DIFFRACTION]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000056157
AA Change: S312L

PolyPhen 2 Score 0.655 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: S312L

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 benign
Transcript: ENSMUST00000120432
AA Change: S312L

PolyPhen 2 Score 0.448 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: S312L

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

Validation Efficiency

100% (63/63)

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: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc9	C	T	6: 142,658,535	R658H	probably benign	Het
Als2cl	C	T	9: 110,898,083	R906C	probably damaging	Het
Asb8	T	C	15: 98,136,401	H91R	probably damaging	Het
Atp8b3	C	T	10: 80,520,024	E1285K	probably benign	Het
Bves	G	A	10: 45,346,290	R172H	possibly damaging	Het
C6	A	T	15: 4,733,695	N59I	probably damaging	Het
Capn15	A	T	17: 25,961,750	V782D	probably damaging	Het
Ccdc18	T	C	5: 108,161,688	L383S	probably benign	Het
Coro6	C	A	11: 77,466,230	N119K	probably benign	Het
Cps1	T	A	1: 67,198,410	D1023E	probably damaging	Het
Dctn1	T	A	6: 83,195,280		probably null	Het
Ero1l	T	A	14: 45,306,583	K55*	probably null	Het
Fam209	G	A	2: 172,472,831	G80D	possibly damaging	Het
Fam71d	C	T	12: 78,719,402	T315I	probably benign	Het
Fam89b	G	A	19: 5,729,248	R94C	probably damaging	Het
Fut1	A	G	7: 45,619,757	*323W	probably null	Het
Gm47985	T	A	1: 151,183,139	F177Y	possibly damaging	Het
Gm8251	T	A	1: 44,057,306	Y1544F	possibly damaging	Het
Gstm7	T	A	3: 107,931,317	D37V	probably damaging	Het
H2-Aa	T	A	17: 34,284,510	S38C	possibly damaging	Het
Ighg2c	T	C	12: 113,288,723	T70A		Het
Ino80	A	G	2: 119,426,587		probably null	Het
Irf8	C	T	8: 120,739,842	R9W	probably damaging	Het
Kcnt2	A	G	1: 140,383,047	N197S	probably damaging	Het
Kif11	T	A	19: 37,384,592	C86*	probably null	Het
Lonp1	A	T	17: 56,626,549	F109I	probably benign	Het
Mroh9	T	A	1: 163,038,956	Q706L	possibly damaging	Het
Mtmr7	T	C	8: 40,555,833	H315R	possibly damaging	Het
Myh7b	G	C	2: 155,614,133	R146P	probably damaging	Het
Naip5	A	G	13: 100,222,347	Y794H	probably benign	Het
Nup153	A	T	13: 46,687,473	N886K	probably benign	Het
Nup205	A	G	6: 35,215,142	R1047G	possibly damaging	Het
Olfr1487	T	A	19: 13,619,626	S155T	probably benign	Het
Olfr768	T	C	10: 129,093,875	Y33C	probably damaging	Het
Oog3	A	T	4: 144,160,457	L31Q	probably damaging	Het
Palmd	T	C	3: 116,923,363	N495S	probably benign	Het
Patj	A	G	4: 98,677,260	Q1070R	probably benign	Het
Pax1	G	A	2: 147,365,904	R232H	probably damaging	Het
Pcdhb1	A	G	18: 37,266,529	N511S	probably damaging	Het
Pigs	C	T	11: 78,341,385	L448F	probably damaging	Het
Pih1d2	A	G	9: 50,621,777	Y235C	probably damaging	Het
Pkd2l2	T	A	18: 34,425,159	I297K	possibly damaging	Het
Pou2f1	C	T	1: 165,915,115	V82I	possibly damaging	Het
Pramel1	T	C	4: 143,396,504	L17P	probably damaging	Het
Riok1	C	T	13: 38,037,015		probably benign	Het
Scg3	C	A	9: 75,661,382	E358*	probably null	Het
Siglec15	T	C	18: 78,048,731	E85G	probably damaging	Het
Snx20	T	C	8: 88,629,978	H70R	probably benign	Het
Spi1	T	A	2: 91,113,340	S76R	probably damaging	Het
Stat5a	T	C	11: 100,879,285	S463P	probably damaging	Het
Svs2	A	G	2: 164,238,206	I13T	unknown	Het
Tmem132e	T	C	11: 82,437,363	S406P	probably damaging	Het
Top1mt	T	C	15: 75,668,711	N237S	possibly damaging	Het
Trav6d-4	G	A	14: 52,753,596	V30M	possibly damaging	Het
Trp73	A	T	4: 154,064,683	M217K	probably damaging	Het
Vmn1r58	A	G	7: 5,411,135	I32T	probably benign	Het
Vmn1r9	T	C	6: 57,071,411	M157T	probably benign	Het
Vmn2r100	C	T	17: 19,531,294	S533F	possibly damaging	Het
Vmn2r112	T	A	17: 22,602,526	M160K	probably benign	Het
Vps13d	C	A	4: 145,163,344	A597S	probably benign	Het
Zfp27	AATCCGCTTGTGCA	AA	7: 29,895,021		probably benign	Het

Other mutations in Mlkl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00089:Mlkl	APN	8	111319428	nonsense	probably null
IGL01376:Mlkl	APN	8	111319747	missense	probably damaging	1.00
IGL02801:Mlkl	APN	8	111316432	missense	probably benign	0.18
IGL02965:Mlkl	APN	8	111331837	missense	probably benign	0.31
IGL03121:Mlkl	APN	8	111314980	missense	probably damaging	1.00
Ghoulish	UTSW	8	111322748	missense	probably damaging	1.00
mecro	UTSW	8	111319716	critical splice donor site	probably null
necro	UTSW	8	111312100	intron	probably benign
secro	UTSW	8	111315567	intron	probably benign
R0133:Mlkl	UTSW	8	111327948	missense	probably damaging	1.00
R0230:Mlkl	UTSW	8	111315062	missense	probably benign	0.07
R0387:Mlkl	UTSW	8	111333350	missense	probably damaging	1.00
R0497:Mlkl	UTSW	8	111327873	missense	probably damaging	1.00
R0735:Mlkl	UTSW	8	111327801	unclassified	probably benign
R1733:Mlkl	UTSW	8	111322748	missense	probably damaging	1.00
R1761:Mlkl	UTSW	8	111333723	missense	possibly damaging	0.81
R1911:Mlkl	UTSW	8	111312100	intron	probably benign
R2057:Mlkl	UTSW	8	111333610	missense	probably benign	0.07
R2921:Mlkl	UTSW	8	111316447	missense	probably benign	0.02
R3745:Mlkl	UTSW	8	111315567	intron	probably benign
R4760:Mlkl	UTSW	8	111319716	critical splice donor site	probably null
R5377:Mlkl	UTSW	8	111327937	missense	probably benign	0.23
R7155:Mlkl	UTSW	8	111319403	missense	probably damaging	1.00
R7459:Mlkl	UTSW	8	111333530	missense	probably benign	0.36
R7728:Mlkl	UTSW	8	111333619	missense	probably damaging	1.00
R8036:Mlkl	UTSW	8	111333454	missense	probably damaging	1.00
R8064:Mlkl	UTSW	8	111312068	missense	probably benign	0.38
R9088:Mlkl	UTSW	8	111322733	missense
R9152:Mlkl	UTSW	8	111319771	missense	probably damaging	1.00
R9275:Mlkl	UTSW	8	111316423	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- GACCCAGTTCTAAAACCCTAGG -3'
(R):5'- GATCTCAGAGATGATGGGACGTC -3'

Sequencing Primer
(F):5'- AGTTCTAAAACCCTAGGTGAGAAC -3'
(R):5'- AGAAGCCCCCGAGTGGTTTC -3'

Posted On

2019-05-13