Mutagenetix > Incidental Mutation

Incidental Mutation 'R0387:Mlkl'

31353

Institutional Source

Beutler Lab

Gene Symbol

Mlkl

Ensembl Gene

ENSMUSG00000012519

Gene Name

mixed lineage kinase domain-like

Synonyms

9130019I15Rik

MMRRC Submission

038593-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.115) question?

Stock #

R0387 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

111311797-111338177 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 111333350 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Lysine at position 135 (E135K)

Ref Sequence

ENSEMBL: ENSMUSP00000113718 (fasta)

Gene Model

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

AlphaFold

Q9D2Y4

Predicted Effect

probably damaging
Transcript: ENSMUST00000056157
AA Change: E135K

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: E135K

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 damaging
Transcript: ENSMUST00000120432
AA Change: E135K

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: E135K

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 damaging
Transcript: ENSMUST00000145862
AA Change: E143K

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000114701
Gene: ENSMUSG00000012519
AA Change: E143K

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

Meta Mutation Damage Score

0.1058

Coding Region Coverage

1x: 98.9%
3x: 97.7%
10x: 94.2%
20x: 85.0%

Validation Efficiency

99% (77/78)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca15	T	G	7: 120,332,852 (GRCm38)		probably null	Het
Abcc9	T	A	6: 142,639,504 (GRCm38)	K825*	probably null	Het
Afp	T	C	5: 90,497,291 (GRCm38)	C189R	probably damaging	Het
Akap9	T	C	5: 3,951,678 (GRCm38)		probably benign	Het
Alpk3	A	T	7: 81,104,227 (GRCm38)	T1652S	possibly damaging	Het
Atg4b	C	A	1: 93,786,556 (GRCm38)	Q354K	probably benign	Het
Atxn2	T	C	5: 121,802,143 (GRCm38)	S388P	possibly damaging	Het
C2cd3	T	A	7: 100,422,507 (GRCm38)		probably benign	Het
Cacna2d2	C	A	9: 107,513,881 (GRCm38)	T403K	probably damaging	Het
Cap2	C	T	13: 46,560,516 (GRCm38)	H79Y	probably damaging	Het
Car10	G	T	11: 93,583,021 (GRCm38)		probably null	Het
Ccno	T	C	13: 112,989,867 (GRCm38)	L290P	probably damaging	Het
Cfap69	T	C	5: 5,589,303 (GRCm38)	K624E	probably damaging	Het
Ctnna3	A	G	10: 64,586,130 (GRCm38)	M568V	probably benign	Het
Cyp1b1	C	A	17: 79,713,774 (GRCm38)	V180L	probably benign	Het
Cyp2u1	G	T	3: 131,295,552 (GRCm38)		probably null	Het
Dcp1a	T	C	14: 30,519,679 (GRCm38)		probably null	Het
Dnm1	C	T	2: 32,320,581 (GRCm38)	G1S	possibly damaging	Het
Dnmt1	A	G	9: 20,918,213 (GRCm38)	L698P	probably damaging	Het
Dock10	C	A	1: 80,540,276 (GRCm38)	C1327F	probably damaging	Het
Dph3b-ps	A	G	13: 106,546,855 (GRCm38)		noncoding transcript	Het
Dpyd	G	A	3: 119,427,226 (GRCm38)	D949N	probably benign	Het
Dync2li1	A	G	17: 84,655,340 (GRCm38)	K345E	possibly damaging	Het
Eml2	T	A	7: 19,182,259 (GRCm38)		probably null	Het
Exoc7	A	G	11: 116,294,401 (GRCm38)		probably benign	Het
Faah	A	T	4: 116,005,692 (GRCm38)	C113*	probably null	Het
Fcf1	T	A	12: 84,973,002 (GRCm38)	D16E	probably benign	Het
Fcgbp	T	C	7: 28,091,454 (GRCm38)		probably benign	Het
Ghr	A	G	15: 3,319,891 (GRCm38)	S602P	probably benign	Het
Gm10334	A	G	6: 41,443,369 (GRCm38)	I141T	possibly damaging	Het
Gm5114	T	C	7: 39,408,809 (GRCm38)	D462G	probably benign	Het
Gm8186	T	A	17: 26,099,026 (GRCm38)	S66C	probably damaging	Het
Gorab	C	T	1: 163,396,834 (GRCm38)	V133M	probably benign	Het
Gria1	G	A	11: 57,309,884 (GRCm38)		probably null	Het
Grik1	T	A	16: 88,034,350 (GRCm38)		probably benign	Het
Gtf3c1	A	G	7: 125,681,104 (GRCm38)	L378P	probably damaging	Het
Htr5b	A	T	1: 121,527,546 (GRCm38)	V215D	probably damaging	Het
Htra1	A	G	7: 130,979,478 (GRCm38)	T319A	probably damaging	Het
Idh2	C	T	7: 80,098,257 (GRCm38)	A232T	probably damaging	Het
Klrb1a	A	C	6: 128,609,734 (GRCm38)	H189Q	possibly damaging	Het
Lhfp	A	G	3: 53,043,328 (GRCm38)	T8A	probably benign	Het
Ly75	T	A	2: 60,306,404 (GRCm38)	Y1493F	probably benign	Het
Mfsd5	T	C	15: 102,281,096 (GRCm38)	I301T	possibly damaging	Het
Mrgprx2	A	C	7: 48,499,160 (GRCm38)	M1R	probably null	Het
Mroh2a	G	C	1: 88,246,042 (GRCm38)	A871P	probably damaging	Het
Mtbp	A	G	15: 55,611,029 (GRCm38)	I280V	possibly damaging	Het
Myo5c	A	T	9: 75,285,021 (GRCm38)		probably benign	Het
Nos3	A	G	5: 24,367,585 (GRCm38)	K174R	probably damaging	Het
Oas2	A	T	5: 120,745,672 (GRCm38)		probably benign	Het
Olfr889	T	A	9: 38,115,770 (GRCm38)		probably null	Het
Pi4kb	G	C	3: 94,984,740 (GRCm38)	E256Q	probably benign	Het
Pik3c2a	T	A	7: 116,373,744 (GRCm38)	I739F	probably damaging	Het
Pla2r1	T	A	2: 60,432,601 (GRCm38)	K1031N	probably benign	Het
Plk4	A	T	3: 40,812,884 (GRCm38)		probably benign	Het
Polq	T	C	16: 37,029,430 (GRCm38)	C349R	probably damaging	Het
Polq	G	T	16: 37,089,317 (GRCm38)	E2354D	probably damaging	Het
Prss22	A	G	17: 23,993,929 (GRCm38)	L278P	probably damaging	Het
Ptprk	G	A	10: 28,354,629 (GRCm38)	V239I	possibly damaging	Het
Raph1	T	G	1: 60,510,496 (GRCm38)		probably benign	Het
Rif1	GCCACCA	GCCA	2: 52,110,324 (GRCm38)		probably benign	Het
Ripor3	C	T	2: 167,983,772 (GRCm38)	W755*	probably null	Het
Rnd3	G	T	2: 51,148,231 (GRCm38)	D77E	probably damaging	Het
Ryr1	T	C	7: 29,083,367 (GRCm38)		probably benign	Het
Serpinb1a	C	T	13: 32,848,738 (GRCm38)	V63I	probably benign	Het
Six1	T	G	12: 73,046,041 (GRCm38)	Y129S	probably damaging	Het
Spata31d1a	G	A	13: 59,703,501 (GRCm38)	T271I	probably damaging	Het
Stab1	T	C	14: 31,148,101 (GRCm38)	D1387G	probably benign	Het
Stra6	T	A	9: 58,153,183 (GRCm38)	M625K	probably benign	Het
Syne1	T	C	10: 5,351,029 (GRCm38)	S900G	probably benign	Het
Tdpoz4	A	C	3: 93,796,700 (GRCm38)	K101N	probably benign	Het
Tigd2	T	C	6: 59,211,158 (GRCm38)	Y337H	probably benign	Het
Tnxb	A	G	17: 34,683,574 (GRCm38)	I1134V	probably benign	Het
Tspyl5	A	G	15: 33,686,935 (GRCm38)	I288T	probably damaging	Het
Ulk1	A	G	5: 110,788,797 (GRCm38)	V61A	possibly damaging	Het
Xxylt1	A	G	16: 30,957,376 (GRCm38)	Y381H	probably benign	Het
Zcchc9	T	A	13: 91,800,947 (GRCm38)	M12L	probably benign	Het
Zfp106	T	C	2: 120,528,472 (GRCm38)		probably null	Het
Zfp74	T	A	7: 29,934,754 (GRCm38)	T510S	probably benign	Het
Zfp808	A	G	13: 62,169,478 (GRCm38)	T14A	probably damaging	Het

Other mutations in Mlkl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00089:Mlkl	APN	8	111,319,428 (GRCm38)	nonsense	probably null
IGL01376:Mlkl	APN	8	111,319,747 (GRCm38)	missense	probably damaging	1.00
IGL02801:Mlkl	APN	8	111,316,432 (GRCm38)	missense	probably benign	0.18
IGL02965:Mlkl	APN	8	111,331,837 (GRCm38)	missense	probably benign	0.31
IGL03121:Mlkl	APN	8	111,314,980 (GRCm38)	missense	probably damaging	1.00
Ghoulish	UTSW	8	111,322,748 (GRCm38)	missense	probably damaging	1.00
mecro	UTSW	8	111,319,716 (GRCm38)	critical splice donor site	probably null
necro	UTSW	8	111,312,100 (GRCm38)	intron	probably benign
secro	UTSW	8	111,315,567 (GRCm38)	intron	probably benign
R0133:Mlkl	UTSW	8	111,327,948 (GRCm38)	missense	probably damaging	1.00
R0230:Mlkl	UTSW	8	111,315,062 (GRCm38)	missense	probably benign	0.07
R0497:Mlkl	UTSW	8	111,327,873 (GRCm38)	missense	probably damaging	1.00
R0735:Mlkl	UTSW	8	111,327,801 (GRCm38)	unclassified	probably benign
R1733:Mlkl	UTSW	8	111,322,748 (GRCm38)	missense	probably damaging	1.00
R1761:Mlkl	UTSW	8	111,333,723 (GRCm38)	missense	possibly damaging	0.81
R1911:Mlkl	UTSW	8	111,312,100 (GRCm38)	intron	probably benign
R2057:Mlkl	UTSW	8	111,333,610 (GRCm38)	missense	probably benign	0.07
R2921:Mlkl	UTSW	8	111,316,447 (GRCm38)	missense	probably benign	0.02
R3745:Mlkl	UTSW	8	111,315,567 (GRCm38)	intron	probably benign
R4760:Mlkl	UTSW	8	111,319,716 (GRCm38)	critical splice donor site	probably null
R5377:Mlkl	UTSW	8	111,327,937 (GRCm38)	missense	probably benign	0.23
R7052:Mlkl	UTSW	8	111,319,442 (GRCm38)	missense	possibly damaging	0.65
R7155:Mlkl	UTSW	8	111,319,403 (GRCm38)	missense	probably damaging	1.00
R7459:Mlkl	UTSW	8	111,333,530 (GRCm38)	missense	probably benign	0.36
R7728:Mlkl	UTSW	8	111,333,619 (GRCm38)	missense	probably damaging	1.00
R8036:Mlkl	UTSW	8	111,333,454 (GRCm38)	missense	probably damaging	1.00
R8064:Mlkl	UTSW	8	111,312,068 (GRCm38)	missense	probably benign	0.38
R9088:Mlkl	UTSW	8	111,322,733 (GRCm38)	missense
R9152:Mlkl	UTSW	8	111,319,771 (GRCm38)	missense	probably damaging	1.00
R9275:Mlkl	UTSW	8	111,316,423 (GRCm38)	missense	probably benign	0.07

Predicted Primers

PCR Primer
(F):5'- GCAGGTAGCAACATGTCCCCTATTC -3'
(R):5'- TGAAGTCCTGAAGGAGGCTAACCAG -3'

Sequencing Primer
(F):5'- ACAGCAGGATTTCTGAATCACAAG -3'
(R):5'- GCTAACCAGCAGATAGAAAAGTTC -3'

Posted On

2013-04-24