Incidental Mutation 'IGL02965:Mlkl'
ID 365520
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Mlkl
Ensembl Gene ENSMUSG00000012519
Gene Name mixed lineage kinase domain-like
Synonyms 9130019I15Rik
Accession Numbers
Essential gene? Probably non essential (E-score: 0.087) question?
Stock # IGL02965
Quality Score
Status
Chromosome 8
Chromosomal Location 112038429-112064809 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 112058469 bp (GRCm39)
Zygosity Heterozygous
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]
AlphaFold Q9D2Y4
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: 110,071,439 (GRCm39) K1471R probably benign Het
Add1 A G 5: 34,777,467 (GRCm39) S77G probably damaging Het
Atm G T 9: 53,364,863 (GRCm39) N2642K probably damaging Het
Atp6v0a2 T A 5: 124,767,267 (GRCm39) M10K possibly damaging Het
Btd T A 14: 31,389,193 (GRCm39) S305T probably damaging Het
Cmya5 C T 13: 93,229,065 (GRCm39) V2008I probably benign Het
Cpd T G 11: 76,681,814 (GRCm39) probably benign Het
Dis3l A G 9: 64,217,766 (GRCm39) F772L probably damaging Het
Dlg5 A T 14: 24,222,091 (GRCm39) I517N probably damaging Het
Fig4 G A 10: 41,161,661 (GRCm39) T34M probably damaging Het
Flna C T X: 73,270,816 (GRCm39) V2235I probably damaging Het
Flot2 T C 11: 77,950,031 (GRCm39) I371T possibly damaging Het
Fsip2 G A 2: 82,813,398 (GRCm39) S3239N probably benign Het
Gbp3 A G 3: 142,273,343 (GRCm39) I297V probably benign Het
Gcnt3 T C 9: 69,942,235 (GRCm39) E111G probably benign Het
Gdi1 G T X: 73,351,331 (GRCm39) A148S probably benign Het
Heatr5b G A 17: 79,060,502 (GRCm39) H2058Y probably benign Het
Hsp90aa1 A G 12: 110,662,113 (GRCm39) M1T probably null Het
Il22b A G 10: 118,130,762 (GRCm39) S45P probably damaging Het
Inppl1 C A 7: 101,477,478 (GRCm39) V715F possibly damaging Het
Kansl1 T C 11: 104,225,991 (GRCm39) Y975C probably damaging Het
Kif18b A G 11: 102,807,338 (GRCm39) probably benign Het
Krt40 T A 11: 99,432,492 (GRCm39) R175W probably damaging Het
Map3k19 T C 1: 127,751,803 (GRCm39) D516G probably damaging Het
Mfsd3 A G 15: 76,587,352 (GRCm39) H345R probably benign Het
Mtnr1a A T 8: 45,522,419 (GRCm39) N58I probably damaging Het
Nsmf T C 2: 24,951,774 (GRCm39) V499A probably damaging Het
Nudt6 A G 3: 37,473,655 (GRCm39) L22P probably damaging Het
Nxf7 T G X: 134,490,159 (GRCm39) E35A probably damaging Het
Or11h23 A C 14: 50,948,653 (GRCm39) I289L probably damaging Het
Paf1 T C 7: 28,095,629 (GRCm39) probably null Het
Pcdhb11 G T 18: 37,557,021 (GRCm39) V784L probably benign Het
Pglyrp2 T C 17: 32,637,560 (GRCm39) D156G probably benign Het
Pnpt1 A G 11: 29,106,939 (GRCm39) D670G probably damaging Het
Polr1b T A 2: 128,967,443 (GRCm39) H945Q probably benign Het
Ptk6 C T 2: 180,840,861 (GRCm39) probably benign Het
Rftn1 C T 17: 50,362,280 (GRCm39) E273K probably benign Het
Rnf125 A G 18: 21,116,168 (GRCm39) I117V probably benign Het
Robo4 A G 9: 37,321,765 (GRCm39) K742R possibly damaging Het
Sez6l T C 5: 112,623,440 (GRCm39) E37G probably damaging Het
Skint4 A T 4: 111,993,218 (GRCm39) I306L probably benign Het
Sntb1 A T 15: 55,506,081 (GRCm39) Y497* probably null Het
Snx27 C A 3: 94,489,733 (GRCm39) V42L probably damaging Het
Sorbs1 T A 19: 40,365,187 (GRCm39) T199S probably benign Het
Sorcs2 A G 5: 36,235,301 (GRCm39) Y72H probably benign Het
Spef2 G T 15: 9,725,192 (GRCm39) probably benign Het
Sucla2 G T 14: 73,816,871 (GRCm39) V204L probably benign Het
Tescl C A 7: 24,033,098 (GRCm39) V76F probably damaging Het
Tnxb T A 17: 34,928,628 (GRCm39) Y2681N possibly damaging Het
Usp42 T C 5: 143,713,769 (GRCm39) T2A probably damaging Het
Vdac3-ps1 T A 13: 18,205,431 (GRCm39) noncoding transcript Het
Wapl T A 14: 34,461,181 (GRCm39) probably benign Het
Other mutations in Mlkl
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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
Posted On 2015-12-18