Mutagenetix > Incidental Mutation

Incidental Mutation 'R1761:Mlkl'

192778

Institutional Source

Beutler Lab

Gene Symbol

Mlkl

Ensembl Gene

ENSMUSG00000012519

Gene Name

mixed lineage kinase domain-like

Synonyms

9130019I15Rik

MMRRC Submission

039793-MU

Accession Numbers

Essential gene?

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

Stock #

R1761 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

112038429-112064809 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 112060355 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Phenylalanine at position 18 (L18F)

Ref Sequence

ENSEMBL: ENSMUSP00000114701 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056157] [ENSMUST00000120432] [ENSMUST00000145862]

AlphaFold

Q9D2Y4

Predicted Effect

probably benign
Transcript: ENSMUST00000056157
AA Change: L10F

PolyPhen 2 Score 0.155 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: L10F

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: L10F

PolyPhen 2 Score 0.155 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: L10F

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

possibly damaging
Transcript: ENSMUST00000145862
AA Change: L18F

PolyPhen 2 Score 0.812 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000114701
Gene: ENSMUSG00000012519
AA Change: L18F

Domain	Start	End	E-Value	Type
PDB:4BTF\|A	9	176	1e-114	PDB

Coding Region Coverage

1x: 97.5%
3x: 96.9%
10x: 95.4%
20x: 92.9%

Validation Efficiency

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abi3bp	C	T	16: 56,488,672 (GRCm39)	H1268Y	possibly damaging	Het
Acan	T	A	7: 78,743,833 (GRCm39)	Y621*	probably null	Het
Aig1	T	C	10: 13,566,328 (GRCm39)	Y152C	probably damaging	Het
Arhgap33	C	T	7: 30,232,488 (GRCm39)		probably null	Het
Bcl6	G	T	16: 23,796,292 (GRCm39)	A45D	probably damaging	Het
Cbx5	T	C	15: 103,121,607 (GRCm39)	D10G	possibly damaging	Het
Ccdc191	A	G	16: 43,763,873 (GRCm39)	I445V	probably benign	Het
Cdk4	T	A	10: 126,900,546 (GRCm39)		probably benign	Het
Chil6	A	G	3: 106,301,654 (GRCm39)	F149L	probably damaging	Het
Cntn5	T	C	9: 10,172,059 (GRCm39)	T42A	probably benign	Het
Cpn2	A	T	16: 30,079,014 (GRCm39)	I229N	probably damaging	Het
Cpne8	A	G	15: 90,532,821 (GRCm39)	V62A	probably damaging	Het
Cr2	A	G	1: 194,837,431 (GRCm39)		probably null	Het
Crnn	A	T	3: 93,055,958 (GRCm39)	H248L	probably benign	Het
Csn1s1	A	G	5: 87,826,894 (GRCm39)	S254G	probably benign	Het
Cubn	A	G	2: 13,494,128 (GRCm39)		probably null	Het
Dnah8	A	G	17: 30,998,890 (GRCm39)	N3525S	probably damaging	Het
Dpp3	A	G	19: 4,971,177 (GRCm39)	L220P	probably benign	Het
Fam110a	T	C	2: 151,812,125 (GRCm39)	E215G	probably benign	Het
Fam20a	A	T	11: 109,568,664 (GRCm39)	N287K	probably damaging	Het
Fat4	T	C	3: 38,941,638 (GRCm39)	V177A	possibly damaging	Het
Fzd8	C	T	18: 9,213,643 (GRCm39)	R242C	probably damaging	Het
Gimap5	A	T	6: 48,730,195 (GRCm39)	Q255L	probably damaging	Het
Gm4787	A	G	12: 81,423,950 (GRCm39)	L736S	probably benign	Het
Gmeb1	G	A	4: 131,962,198 (GRCm39)	Q154*	probably null	Het
Gpr156	T	C	16: 37,807,929 (GRCm39)	L192P	probably damaging	Het
Gpr179	A	C	11: 97,225,932 (GRCm39)	S2074R	probably benign	Het
Hddc2	G	T	10: 31,202,135 (GRCm39)	D161Y	probably damaging	Het
Hlcs	T	C	16: 94,068,866 (GRCm39)	D265G	probably benign	Het
Hspg2	A	T	4: 137,241,984 (GRCm39)	I573F	possibly damaging	Het
Il1b	T	C	2: 129,207,101 (GRCm39)	K220E	probably damaging	Het
Il5	T	C	11: 53,614,557 (GRCm39)	I66T	probably damaging	Het
Irf6	G	A	1: 192,851,609 (GRCm39)	R400H	probably damaging	Het
Klra1	A	T	6: 130,349,836 (GRCm39)	Y201N	probably damaging	Het
Lmf2	A	G	15: 89,236,916 (GRCm39)	V442A	possibly damaging	Het
Mcm2	T	C	6: 88,866,770 (GRCm39)	I412M	possibly damaging	Het
Mug2	C	A	6: 122,051,664 (GRCm39)	H949N	probably benign	Het
Nf1	T	C	11: 79,275,091 (GRCm39)	F51L	probably damaging	Het
Or52j3	T	G	7: 102,836,325 (GRCm39)	C172W	probably damaging	Het
Or7d10	A	T	9: 19,832,445 (GRCm39)	*313C	probably null	Het
Or8k18	T	G	2: 86,085,383 (GRCm39)	Y218S	probably damaging	Het
P3h2	T	C	16: 25,803,800 (GRCm39)	E322G	probably damaging	Het
Pramel21	T	C	4: 143,342,438 (GRCm39)	Y182H	probably benign	Het
Psmg2	CTTCAGTT	CTTCAGTTCAGTT	18: 67,779,095 (GRCm39)		probably null	Het
Ptdss1	T	C	13: 67,104,476 (GRCm39)	V116A	possibly damaging	Het
Ranbp2	T	C	10: 58,321,563 (GRCm39)	V2620A	probably benign	Het
Robo2	A	G	16: 73,831,912 (GRCm39)	V256A	probably damaging	Het
Scg3	T	A	9: 75,584,040 (GRCm39)	I154F	probably damaging	Het
Scgn	A	T	13: 24,143,689 (GRCm39)	F225Y	probably damaging	Het
Sec61b	T	C	4: 47,480,137 (GRCm39)	C58R	possibly damaging	Het
Slc25a46	G	T	18: 31,740,315 (GRCm39)	Q96K	possibly damaging	Het
Spmip6	G	A	4: 41,507,223 (GRCm39)	P109L	probably damaging	Het
Sptb	A	G	12: 76,659,382 (GRCm39)	F1173L	probably damaging	Het
Srcap	T	A	7: 127,134,017 (GRCm39)	C893S	probably damaging	Het
Tet3	T	C	6: 83,380,641 (GRCm39)	E509G	probably damaging	Het
Timm10b	C	T	7: 105,332,915 (GRCm39)	R897*	probably null	Het
Tln2	C	T	9: 67,193,796 (GRCm39)	A1773T	probably benign	Het
Tom1	T	C	8: 75,778,179 (GRCm39)	V87A	probably benign	Het
Tti1	T	C	2: 157,849,617 (GRCm39)	I541V	probably benign	Het
Ttn	A	T	2: 76,641,587 (GRCm39)	L5176Q	possibly damaging	Het
Tubb1	A	G	2: 174,298,689 (GRCm39)	S124G	probably benign	Het
Vgll3	A	T	16: 65,636,614 (GRCm39)	D310V	probably damaging	Het
Vmac	A	G	17: 57,022,788 (GRCm39)	L74P	probably damaging	Het
Zbtb1	A	T	12: 76,432,595 (GRCm39)	K194*	probably null	Het
Zfp429	A	G	13: 67,544,195 (GRCm39)	M76T	probably benign	Het
Zfp808	T	A	13: 62,319,460 (GRCm39)	C230S	possibly damaging	Het
Zfp980	A	G	4: 145,428,612 (GRCm39)	Y447C	probably damaging	Het
Zfp985	A	G	4: 147,668,502 (GRCm39)	T457A	probably benign	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
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
R4760:Mlkl	UTSW	8	112,046,348 (GRCm39)	critical splice donor site	probably null
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'- TGGCTGACATCTGAAACGGTATTCC -3'
(R):5'- TGTGGCACACCTCAAACTGTCTC -3'

Sequencing Primer
(F):5'- CCAAATATGGGACTTCTTGCTG -3'
(R):5'- AAACTGTCTCTGTCTTGCACG -3'

Posted On

2014-05-23