Mutagenetix > Incidental Mutation

Incidental Mutation 'R1733:Mlkl'

199491

Institutional Source

Beutler Lab

Gene Symbol

Mlkl

Ensembl Gene

ENSMUSG00000012519

Gene Name

mixed lineage kinase domain-like

Synonyms

9130019I15Rik

MMRRC Submission

039765-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.105) question?

Stock #

R1733 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

111311797-111338177 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 111322748 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 248 (S248P)

Ref Sequence

ENSEMBL: ENSMUSP00000113718 (fasta)

Gene Model

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

AlphaFold

Q9D2Y4

Predicted Effect

probably damaging
Transcript: ENSMUST00000056157
AA Change: S248P

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

SMART Domains

Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: S248P

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: S248P

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

SMART Domains

Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: S248P

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: ENSMUST00000212417

Meta Mutation Damage Score

0.8982

Coding Region Coverage

1x: 97.5%
3x: 96.9%
10x: 95.2%
20x: 91.9%

Validation Efficiency

95% (95/100)

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamts19	T	G	18: 59,031,929	C1034W	probably damaging	Het
Agbl2	G	T	2: 90,810,745	K737N	probably damaging	Het
Aqp9	T	A	9: 71,112,342	I279F	possibly damaging	Het
Aspm	T	A	1: 139,457,117	N166K	probably benign	Het
Atp13a3	A	T	16: 30,357,266	I186N	probably benign	Het
Btaf1	A	T	19: 36,994,962	I1366L	probably benign	Het
Camk4	A	C	18: 33,078,021	K60Q	possibly damaging	Het
Card11	G	T	5: 140,906,633	Q226K	possibly damaging	Het
Ccdc187	T	C	2: 26,293,658	D110G	possibly damaging	Het
Col5a2	C	T	1: 45,407,032	R462Q	possibly damaging	Het
Cp	A	T	3: 19,968,219		probably benign	Het
Cpz	A	T	5: 35,517,758	V38E	probably damaging	Het
Cxcr6	G	A	9: 123,810,116	V68I	probably damaging	Het
Cyp2a22	C	A	7: 26,934,762	E322D	possibly damaging	Het
D130052B06Rik	C	T	11: 33,623,784	T127I	probably benign	Het
Daam2	T	A	17: 49,490,203	M185L	possibly damaging	Het
Dnaja3	G	A	16: 4,684,165	R11K	probably null	Het
Dnttip2	T	A	3: 122,276,748	S537R	probably benign	Het
Dock9	G	T	14: 121,626,880	H572Q	probably benign	Het
Dpp4	T	A	2: 62,372,869		probably null	Het
Enc1	T	G	13: 97,245,042	I20S	possibly damaging	Het
Ephb6	T	A	6: 41,619,720	H900Q	probably benign	Het
Ercc3	T	C	18: 32,267,165	V690A	possibly damaging	Het
Fam90a1a	C	T	8: 21,963,369	Q247*	probably null	Het
Fkbp10	G	A	11: 100,423,931	R423H	probably benign	Het
Fus	A	G	7: 127,981,545	M265V	probably benign	Het
Gas2l3	T	A	10: 89,414,265	K330N	probably damaging	Het
Gpam	T	G	19: 55,081,469	L410F	probably damaging	Het
Gpr37l1	A	T	1: 135,161,535	V264E	possibly damaging	Het
Grk6	A	T	13: 55,453,166		probably benign	Het
Gsto1	G	T	19: 47,855,235	V19F	probably damaging	Het
H1fnt	G	T	15: 98,256,135	Q378K	unknown	Het
Hgfac	G	A	5: 35,043,674	C194Y	probably damaging	Het
Hivep1	A	G	13: 42,157,931	N1216D	probably damaging	Het
Hrg	C	T	16: 22,951,247	A42V	probably damaging	Het
Irx4	A	G	13: 73,266,705	D136G	probably benign	Het
Kcnn3	G	T	3: 89,652,090	V556L	probably benign	Het
Klk8	T	C	7: 43,802,121	Y179H	possibly damaging	Het
Klrb1f	T	A	6: 129,054,359	L173*	probably null	Het
Kremen2	A	T	17: 23,743,399		probably null	Het
Krt25	A	T	11: 99,316,552	Y400*	probably null	Het
Lingo4	A	T	3: 94,403,178	R474S	probably benign	Het
Lnpep	T	C	17: 17,553,313	K599E	probably benign	Het
Mapk8ip3	A	T	17: 24,936,850	M2K	possibly damaging	Het
Mat2b	A	T	11: 40,680,077	S307T	probably benign	Het
Mcph1	C	A	8: 18,631,963	A372D	probably benign	Het
Mfsd6	T	A	1: 52,709,365	I114F	probably damaging	Het
Mmrn1	A	T	6: 60,977,101	T789S	probably benign	Het
Mphosph8	A	G	14: 56,693,459	Y735C	probably damaging	Het
Mrc1	T	A	2: 14,257,099	Y300N	probably damaging	Het
Mrps11	A	G	7: 78,792,712	H180R	probably damaging	Het
Msh4	T	C	3: 153,867,767	D556G	probably damaging	Het
Myh10	C	A	11: 68,802,296	D1472E	probably benign	Het
Myo16	T	C	8: 10,442,283	S742P	probably damaging	Het
Nlrp5-ps	C	T	7: 14,583,053		noncoding transcript	Het
Nrp1	C	T	8: 128,468,493	P477S	probably benign	Het
Olfr1278	T	C	2: 111,292,865	V199A	probably damaging	Het
Olfr1307	T	A	2: 111,945,280	M59L	probably benign	Het
Olfr64	T	C	7: 103,892,911	S275G	probably benign	Het
Olfr936	G	T	9: 39,047,382	H57N	unknown	Het
Oplah	G	T	15: 76,302,483	C665*	probably null	Het
Otogl	T	C	10: 107,783,712	T1696A	possibly damaging	Het
Pdzrn4	A	G	15: 92,401,974	I242V	probably benign	Het
Phgdh	G	A	3: 98,328,135	T141I	probably benign	Het
Pigv	T	C	4: 133,664,926	Y311C	probably damaging	Het
Pik3c2a	T	G	7: 116,418,520	M1L	possibly damaging	Het
Pitpnm1	A	T	19: 4,109,960	K760*	probably null	Het
Pnrc1	G	A	4: 33,246,438	H174Y	probably damaging	Het
Ptgis	A	G	2: 167,191,968		probably benign	Het
Ptpn4	T	C	1: 119,716,043		probably null	Het
Rin3	T	A	12: 102,369,330	L420*	probably null	Het
Sacs	T	G	14: 61,205,454	F1650V	probably damaging	Het
Sbno2	T	A	10: 80,058,508	N1081Y	possibly damaging	Het
Sema5b	C	T	16: 35,646,367	P213L	probably damaging	Het
Sharpin	T	C	15: 76,347,936	K240R	probably benign	Het
Skint6	T	A	4: 113,177,037		probably benign	Het
Slc4a2	A	G	5: 24,429,567	E68G	probably damaging	Het
Srcin1	C	T	11: 97,533,501	V634I	probably benign	Het
Srsf10	T	A	4: 135,863,165	F134I	possibly damaging	Het
Stab1	C	A	14: 31,145,303	G1700V	probably damaging	Het
Sun1	T	G	5: 139,230,789	C290W	possibly damaging	Het
Svs6	T	A	2: 164,317,657		probably benign	Het
Tmem8b	G	A	4: 43,690,228		probably null	Het
Usp49	A	G	17: 47,672,313	D81G	probably damaging	Het
Vmn1r215	T	A	13: 23,076,678	V296D	probably benign	Het
Vmn1r6	T	A	6: 57,002,622	S90T	probably damaging	Het
Wbp2	A	G	11: 116,083,883	F42L	probably benign	Het
Wdr20rt	C	T	12: 65,227,281	T333I	possibly damaging	Het
Zfp341	C	T	2: 154,641,378	A552V	probably benign	Het
Zfp607b	A	T	7: 27,692,524	H8L	possibly damaging	Het
Zfp758	G	T	17: 22,375,849	D439Y	probably damaging	Het
Zfp946	T	C	17: 22,453,557	Y46H	probably damaging	Het
Zic2	G	A	14: 122,478,947	E432K	probably damaging	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
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
R7052:Mlkl	UTSW	8	111319442	missense	possibly damaging	0.65
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'- TGTGGCTGACCTCCATGCTTAAATC -3'
(R):5'- CTGCCTCCAAGTTCATCTGGGAAG -3'

Sequencing Primer
(F):5'- TGACCTCCATGCTTAAATCGAAAAG -3'
(R):5'- GTTAGATTTACAGCCAAGCCTGTC -3'

Posted On

2014-05-23