Incidental Mutation 'IGL02965:Mlkl'
ID365520
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Mlkl
Ensembl Gene ENSMUSG00000012519
Gene Namemixed lineage kinase domain-like
Synonyms9130019I15Rik
Accession Numbers
Is this an essential gene? Probably non essential (E-score: 0.074) question?
Stock #IGL02965
Quality Score
Status
Chromosome8
Chromosomal Location111311797-111338177 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to T at 111331837 bp
ZygosityHeterozygous
Amino Acid Change Isoleucine to Asparagine at position 162 (I162N)
Ref Sequence ENSEMBL: ENSMUSP00000113718 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000056157] [ENSMUST00000120432] [ENSMUST00000145862]
Predicted Effect probably benign
Transcript: ENSMUST00000056157
AA Change: I162N

PolyPhen 2 Score 0.307 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: I162N

DomainStartEndE-ValueType
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: I162N

PolyPhen 2 Score 0.307 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: I162N

DomainStartEndE-ValueType
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: I170N

PolyPhen 2 Score 0.275 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000114701
Gene: ENSMUSG00000012519
AA Change: I170N

DomainStartEndE-ValueType
PDB:4BTF|A 9 176 1e-114 PDB
Coding Region Coverage
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: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca6 T C 11: 110,180,613 K1471R probably benign Het
Add1 A G 5: 34,620,123 S77G probably damaging Het
Atm G T 9: 53,453,563 N2642K probably damaging Het
Atp6v0a2 T A 5: 124,629,202 M10K possibly damaging Het
Btd T A 14: 31,667,236 S305T probably damaging Het
Cmya5 C T 13: 93,092,557 V2008I probably benign Het
Cpd T G 11: 76,790,988 probably benign Het
Dis3l A G 9: 64,310,484 F772L probably damaging Het
Dlg5 A T 14: 24,172,023 I517N probably damaging Het
Fig4 G A 10: 41,285,665 T34M probably damaging Het
Flna C T X: 74,227,210 V2235I probably damaging Het
Flot2 T C 11: 78,059,205 I371T possibly damaging Het
Fsip2 G A 2: 82,983,054 S3239N probably benign Het
Gbp3 A G 3: 142,567,582 I297V probably benign Het
Gcnt3 T C 9: 70,034,953 E111G probably benign Het
Gdi1 G T X: 74,307,725 A148S probably benign Het
Heatr5b G A 17: 78,753,073 H2058Y probably benign Het
Hsp90aa1 A G 12: 110,695,679 M1T probably null Het
Iltifb A G 10: 118,294,857 S45P probably damaging Het
Inppl1 C A 7: 101,828,271 V715F possibly damaging Het
Kansl1 T C 11: 104,335,165 Y975C probably damaging Het
Kif18b A G 11: 102,916,512 probably benign Het
Krt40 T A 11: 99,541,666 R175W probably damaging Het
Map3k19 T C 1: 127,824,066 D516G probably damaging Het
Mfsd3 A G 15: 76,703,152 H345R probably benign Het
Mtnr1a A T 8: 45,069,382 N58I probably damaging Het
Nsmf T C 2: 25,061,762 V499A probably damaging Het
Nudt6 A G 3: 37,419,506 L22P probably damaging Het
Nxf7 T G X: 135,589,410 E35A probably damaging Het
Olfr748 A C 14: 50,711,196 I289L probably damaging Het
Paf1 T C 7: 28,396,204 probably null Het
Pcdhb11 G T 18: 37,423,968 V784L probably benign Het
Pglyrp2 T C 17: 32,418,586 D156G probably benign Het
Pnpt1 A G 11: 29,156,939 D670G probably damaging Het
Polr1b T A 2: 129,125,523 H945Q probably benign Het
Ptk6 C T 2: 181,199,068 probably benign Het
Rftn1 C T 17: 50,055,252 E273K probably benign Het
Rnf125 A G 18: 20,983,111 I117V probably benign Het
Robo4 A G 9: 37,410,469 K742R possibly damaging Het
Sez6l T C 5: 112,475,574 E37G probably damaging Het
Skint4 A T 4: 112,136,021 I306L probably benign Het
Sntb1 A T 15: 55,642,685 Y497* probably null Het
Snx27 C A 3: 94,582,426 V42L probably damaging Het
Sorbs1 T A 19: 40,376,743 T199S probably benign Het
Sorcs2 A G 5: 36,077,957 Y72H probably benign Het
Spef2 G T 15: 9,725,106 probably benign Het
Sucla2 G T 14: 73,579,431 V204L probably benign Het
Tescl C A 7: 24,333,673 V76F probably damaging Het
Tnxb T A 17: 34,709,654 Y2681N possibly damaging Het
Usp42 T C 5: 143,728,014 T2A probably damaging Het
Vdac3-ps1 T A 13: 18,030,846 noncoding transcript Het
Wapl T A 14: 34,739,224 probably benign Het
Other mutations in Mlkl
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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
Posted On2015-12-18