Mutagenetix > Incidental Mutation

Incidental Mutation 'R2057:Mlkl'

228270

Institutional Source

Beutler Lab

Gene Symbol

Mlkl

Ensembl Gene

ENSMUSG00000012519

Gene Name

mixed lineage kinase domain-like

Synonyms

9130019I15Rik

MMRRC Submission

040062-MU

Accession Numbers

Essential gene?

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

Stock #

R2057 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

112038429-112064809 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 112060242 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Arginine at position 48 (Q48R)

Ref Sequence

ENSEMBL: ENSMUSP00000113718 (fasta)

Gene Model

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

AlphaFold

Q9D2Y4

Predicted Effect

probably benign
Transcript: ENSMUST00000056157
AA Change: Q48R

PolyPhen 2 Score 0.069 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: Q48R

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: Q48R

PolyPhen 2 Score 0.069 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: Q48R

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

probably benign
Transcript: ENSMUST00000145862
AA Change: Q56R

PolyPhen 2 Score 0.016 (Sensitivity: 0.95; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000114701
Gene: ENSMUSG00000012519
AA Change: Q56R

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

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.4%
20x: 95.5%

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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc2	A	G	19: 43,806,477 (GRCm39)	K764E	probably damaging	Het
Abcg2	T	C	6: 58,667,525 (GRCm39)	V129A	probably benign	Het
Adgrf5	A	G	17: 43,739,477 (GRCm39)	Y72C	possibly damaging	Het
Ago1	C	T	4: 126,337,021 (GRCm39)	R228H	probably damaging	Het
Ano1	A	G	7: 144,201,789 (GRCm39)	V334A	probably damaging	Het
Apob	A	T	12: 8,052,164 (GRCm39)	R1202*	probably null	Het
Arfgap3	G	T	15: 83,194,501 (GRCm39)	D389E	probably benign	Het
Atf6b	A	T	17: 34,867,549 (GRCm39)		probably null	Het
Atoh8	T	C	6: 72,212,112 (GRCm39)	K13E	probably damaging	Het
Bicral	G	T	17: 47,135,814 (GRCm39)	N465K	possibly damaging	Het
Bves	T	A	10: 45,219,231 (GRCm39)	Y110N	probably damaging	Het
C4b	A	G	17: 34,947,594 (GRCm39)	Y1695H	probably damaging	Het
Cage1	A	G	13: 38,207,356 (GRCm39)	V163A	probably benign	Het
Canx	T	C	11: 50,195,252 (GRCm39)	N272S	probably damaging	Het
Caskin1	G	T	17: 24,715,433 (GRCm39)	G93V	probably damaging	Het
Cd34	T	C	1: 194,641,450 (GRCm39)	V292A	probably damaging	Het
Cd84	A	G	1: 171,700,317 (GRCm39)	T145A	possibly damaging	Het
Cdh16	C	A	8: 105,348,597 (GRCm39)	G144*	probably null	Het
Chaf1b	T	A	16: 93,691,795 (GRCm39)	H280Q	probably damaging	Het
Chpf2	G	A	5: 24,796,220 (GRCm39)	G389R	probably damaging	Het
Crb1	T	C	1: 139,242,488 (GRCm39)	Y330C	probably damaging	Het
Cux2	A	T	5: 122,007,567 (GRCm39)	V698E	probably benign	Het
Dhtkd1	A	G	2: 5,947,430 (GRCm39)	V18A	unknown	Het
Dmbt1	G	A	7: 130,707,900 (GRCm39)	A1381T	possibly damaging	Het
Enpp1	C	G	10: 24,536,090 (GRCm39)	A437P	probably damaging	Het
Fat2	C	T	11: 55,172,686 (GRCm39)	V2676I	possibly damaging	Het
Fzd2	A	G	11: 102,496,759 (GRCm39)	D401G	probably damaging	Het
Gcm2	T	C	13: 41,263,430 (GRCm39)	M1V	probably null	Het
Gnai3	C	T	3: 108,019,812 (GRCm39)	V233I	probably benign	Het
Golim4	T	A	3: 75,802,194 (GRCm39)	D366V	possibly damaging	Het
Grin1	T	A	2: 25,206,832 (GRCm39)	T110S	probably damaging	Het
Grin2a	A	G	16: 9,487,608 (GRCm39)	V430A	probably benign	Het
Gstp3	G	A	19: 4,109,282 (GRCm39)	T5I	probably damaging	Het
Il17rb	T	A	14: 29,719,111 (GRCm39)	M324L	probably benign	Het
Jmy	A	G	13: 93,596,211 (GRCm39)	Y473H	probably damaging	Het
Khdc1b	A	G	1: 21,454,534 (GRCm39)	D79G	probably benign	Het
Kremen2	T	C	17: 23,961,691 (GRCm39)	E272G	possibly damaging	Het
Lmo7	G	C	14: 102,124,614 (GRCm39)	A358P	probably damaging	Het
Mdh1b	T	C	1: 63,760,741 (GRCm39)	I107V	probably benign	Het
Myh2	G	A	11: 67,079,665 (GRCm39)		probably null	Het
Naip1	T	A	13: 100,562,081 (GRCm39)	Q1028L	probably damaging	Het
Ncald	T	A	15: 37,397,423 (GRCm39)	I86F	possibly damaging	Het
Nid1	A	C	13: 13,675,058 (GRCm39)	H926P	probably benign	Het
Nlrp9a	T	A	7: 26,256,787 (GRCm39)	I46K	possibly damaging	Het
Or1p1	A	G	11: 74,179,652 (GRCm39)	Y60C	probably damaging	Het
Or9r3	A	T	10: 129,947,859 (GRCm39)	S267T	probably benign	Het
Pak1	T	A	7: 97,557,004 (GRCm39)		probably null	Het
Parpbp	T	A	10: 87,960,824 (GRCm39)	M221L	probably benign	Het
Pde12	T	C	14: 26,390,035 (GRCm39)	I225V	probably benign	Het
Phf19	G	T	2: 34,789,620 (GRCm39)	R367S	probably benign	Het
Plcl2	A	G	17: 50,975,139 (GRCm39)		probably null	Het
Plxnb1	A	T	9: 108,938,294 (GRCm39)	I1283F	possibly damaging	Het
Pramel6	T	A	2: 87,339,059 (GRCm39)	N86K	possibly damaging	Het
Prkdc	A	G	16: 15,545,469 (GRCm39)	T1862A	probably benign	Het
Prpf40a	A	T	2: 53,034,851 (GRCm39)	I779K	probably damaging	Het
Prss3b	G	A	6: 41,009,315 (GRCm39)	T173I	probably benign	Het
Ptpn20	A	T	14: 33,352,942 (GRCm39)	E227V	probably damaging	Het
Rad54b	C	T	4: 11,606,088 (GRCm39)	R499C	probably benign	Het
Rarg	C	A	15: 102,147,939 (GRCm39)	A291S	probably damaging	Het
Rnf169	A	T	7: 99,574,615 (GRCm39)	L660Q	probably damaging	Het
Scn4a	A	G	11: 106,226,550 (GRCm39)	V670A	probably damaging	Het
Serpinb9c	A	T	13: 33,340,854 (GRCm39)	C81*	probably null	Het
Sik1	A	G	17: 32,067,771 (GRCm39)	S435P	probably benign	Het
Slc35g2	G	A	9: 100,435,329 (GRCm39)	A114V	probably damaging	Het
Slc7a14	A	T	3: 31,291,645 (GRCm39)	V211E	probably damaging	Het
Snrpn	A	T	7: 59,637,204 (GRCm39)	H37Q	possibly damaging	Het
Spock3	T	A	8: 63,698,204 (GRCm39)	C185*	probably null	Het
Tbc1d4	A	G	14: 101,714,591 (GRCm39)	S627P	probably damaging	Het
Tgoln1	T	C	6: 72,592,653 (GRCm39)	T276A	probably benign	Het
Tmem176b	G	A	6: 48,813,267 (GRCm39)	T64I	probably damaging	Het
Tnpo2	T	C	8: 85,776,742 (GRCm39)	L483P	probably damaging	Het
Tpte	T	A	8: 22,808,355 (GRCm39)	D163E	probably benign	Het
Trim36	A	T	18: 46,329,229 (GRCm39)	D70E	probably benign	Het
Umodl1	G	A	17: 31,227,740 (GRCm39)		probably null	Het
Wdr90	T	C	17: 26,074,173 (GRCm39)	T691A	probably benign	Het
Zdhhc8	A	G	16: 18,046,210 (GRCm39)	S118P	probably damaging	Het
Zfp438	T	C	18: 5,214,085 (GRCm39)	E291G	probably benign	Het
Zfp879	C	T	11: 50,723,428 (GRCm39)	E543K	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
R1761:Mlkl	UTSW	8	112,060,355 (GRCm39)	missense	possibly damaging	0.81
R1911:Mlkl	UTSW	8	112,038,732 (GRCm39)	intron	probably benign
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'- GATAAACCTGAAGCAGCAGC -3'
(R):5'- ACAGGGGATTGTGGTATTTCAAC -3'

Sequencing Primer
(F):5'- AGCTCCTCCCAGACGTC -3'
(R):5'- GGTATTTCAACCAGTCTATGCATC -3'

Posted On

2014-09-17