Incidental Mutation 'IGL03121:Mlkl'
ID 409978
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 # IGL03121
Quality Score
Status
Chromosome 8
Chromosomal Location 112038429-112064809 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 112041612 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Tryptophan at position 443 (R443W)
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: R443W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: R443W

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 damaging
Transcript: ENSMUST00000120432
AA Change: R443W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: R443W

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 noncoding transcript
Transcript: ENSMUST00000135710
Predicted Effect noncoding transcript
Transcript: ENSMUST00000212417
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: 32 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700012B09Rik A G 9: 14,672,946 (GRCm39) S4P possibly damaging Het
A2m A G 6: 121,618,265 (GRCm39) N186S probably benign Het
Afg2a T C 3: 37,518,800 (GRCm39) I778T probably damaging Het
Ago1 T C 4: 126,353,796 (GRCm39) K261R probably benign Het
Alas1 G A 9: 106,124,113 (GRCm39) P15L probably damaging Het
Aox1 G A 1: 58,398,113 (GRCm39) V1285M probably damaging Het
Brd8 A T 18: 34,739,740 (GRCm39) F678I probably damaging Het
Col27a1 T A 4: 63,143,446 (GRCm39) M378K probably benign Het
Dpy19l4 C A 4: 11,303,334 (GRCm39) V196F probably damaging Het
Dst G T 1: 34,256,884 (GRCm39) probably benign Het
Hsd17b1 T A 11: 100,970,870 (GRCm39) Y275* probably null Het
Kdm3b A G 18: 34,928,762 (GRCm39) E171G probably damaging Het
Klc1 T C 12: 111,748,076 (GRCm39) probably benign Het
Mov10 A T 3: 104,708,318 (GRCm39) V477E probably benign Het
Nacad A G 11: 6,550,933 (GRCm39) S753P probably damaging Het
Ncapd2 A C 6: 125,150,575 (GRCm39) M842R probably benign Het
Nkd2 C A 13: 73,969,498 (GRCm39) A311S probably benign Het
Nrg1 A G 8: 32,314,608 (GRCm39) probably benign Het
Or4f6 A G 2: 111,838,953 (GRCm39) Y193H probably benign Het
Or6c68 A G 10: 129,158,037 (GRCm39) I182V probably benign Het
Pde6h A G 6: 136,936,280 (GRCm39) S8G probably null Het
Pik3c2b A G 1: 133,007,483 (GRCm39) K616E probably benign Het
Pnpt1 A T 11: 29,082,845 (GRCm39) R54S probably benign Het
Pramel38 T C 5: 94,368,912 (GRCm39) V469A possibly damaging Het
Rttn A G 18: 88,993,875 (GRCm39) D184G probably damaging Het
Skint5 T A 4: 113,574,284 (GRCm39) I756F unknown Het
Slc24a2 T C 4: 87,145,143 (GRCm39) T304A probably benign Het
Stk3 A T 15: 35,099,572 (GRCm39) probably benign Het
Trim69 A G 2: 121,998,128 (GRCm39) I33M probably benign Het
Ube2q2 A T 9: 55,102,323 (GRCm39) probably benign Het
Vmn1r67 T A 7: 10,181,394 (GRCm39) N158K probably benign Het
Wipi2 G A 5: 142,648,857 (GRCm39) E252K 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
IGL02965:Mlkl APN 8 112,058,469 (GRCm39) missense probably benign 0.31
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 2016-08-02