Incidental Mutation 'R8064:Mlkl'
ID 619907
Institutional Source Beutler Lab
Gene Symbol Mlkl
Ensembl Gene ENSMUSG00000012519
Gene Name mixed lineage kinase domain-like
Synonyms 9130019I15Rik
MMRRC Submission 067500-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.087) question?
Stock # R8064 (G1)
Quality Score 225.009
Status Not validated
Chromosome 8
Chromosomal Location 112038429-112064809 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 112038700 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Valine at position 459 (E459V)
Ref Sequence ENSEMBL: ENSMUSP00000055521 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000056157] [ENSMUST00000120432]
AlphaFold Q9D2Y4
PDB Structure Structure of MLKL [X-RAY DIFFRACTION]
Crystal structure of the mouse MLKL kinase-like domain [X-RAY DIFFRACTION]
Crystal structure of the mouse RIP3-MLKL complex [X-RAY DIFFRACTION]
Predicted Effect probably benign
Transcript: ENSMUST00000056157
AA Change: E459V

PolyPhen 2 Score 0.380 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: E459V

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: E451V

PolyPhen 2 Score 0.398 (Sensitivity: 0.89; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: E451V

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
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: 46 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam3 A T 8: 25,171,566 (GRCm39) V755D probably benign Het
Adgrb3 A T 1: 25,459,637 (GRCm39) probably null Het
Anapc2 T C 2: 25,166,418 (GRCm39) V395A probably benign Het
Apol11b A G 15: 77,519,417 (GRCm39) V221A not run Het
Arhgef28 T A 13: 98,115,002 (GRCm39) Y616F probably benign Het
Brdt C A 5: 107,525,862 (GRCm39) S905* probably null Het
Ccdc54 T A 16: 50,410,327 (GRCm39) H313L probably benign Het
Chuk A G 19: 44,071,115 (GRCm39) L530P probably damaging Het
Csl A T 10: 99,594,407 (GRCm39) N219K probably damaging Het
Cyp2j5 A G 4: 96,546,948 (GRCm39) S189P probably damaging Het
Cyp4a14 A T 4: 115,352,155 (GRCm39) C86S probably benign Het
Dgkg TCTCCT TCT 16: 22,399,344 (GRCm39) probably null Het
F11 C T 8: 45,698,810 (GRCm39) G445S probably benign Het
Fer T A 17: 64,214,418 (GRCm39) I117N probably benign Het
Gpat3 A T 5: 101,039,522 (GRCm39) I290F probably benign Het
H2-M10.2 C T 17: 36,595,442 (GRCm39) V283M probably damaging Het
Hpse G A 5: 100,836,766 (GRCm39) P408S probably benign Het
Hyou1 T A 9: 44,296,882 (GRCm39) N515K possibly damaging Het
Idh1 A G 1: 65,205,338 (GRCm39) L209P probably damaging Het
Igkv16-104 A T 6: 68,402,875 (GRCm39) Y56F possibly damaging Het
Ins2 A G 7: 142,232,553 (GRCm39) L77P probably benign Het
Kcnn2 A T 18: 45,692,426 (GRCm39) M1L probably benign Het
Kdm3b A T 18: 34,946,460 (GRCm39) probably null Het
Lysmd4 T C 7: 66,873,398 (GRCm39) F11S probably damaging Het
Macf1 T A 4: 123,353,167 (GRCm39) D3625V possibly damaging Het
Nsd3 A T 8: 26,190,698 (GRCm39) K210* probably null Het
Or10ag57 C T 2: 87,218,853 (GRCm39) T268I probably benign Het
Or10q1b T C 19: 13,682,386 (GRCm39) F65S probably damaging Het
Or52n4 T A 7: 104,294,561 (GRCm39) Q6L probably benign Het
Pcsk5 T C 19: 17,692,225 (GRCm39) N153S probably damaging Het
Rac3 T A 11: 120,614,401 (GRCm39) V182E probably benign Het
Ripk3 T G 14: 56,025,383 (GRCm39) E60D possibly damaging Het
Sacs T A 14: 61,429,624 (GRCm39) I561N possibly damaging Het
Smad7 A G 18: 75,527,153 (GRCm39) Y333C probably damaging Het
Snhg11 T G 2: 158,218,121 (GRCm39) M1R probably null Het
Sp100 C T 1: 85,608,860 (GRCm39) R330* probably null Het
Spen T C 4: 141,203,011 (GRCm39) K1872R possibly damaging Het
Spon1 T A 7: 113,635,856 (GRCm39) I690N probably damaging Het
Taok1 G A 11: 77,440,130 (GRCm39) R626* probably null Het
Tecta C T 9: 42,306,251 (GRCm39) G59D possibly damaging Het
Tmem8b T C 4: 43,690,139 (GRCm39) F399S probably damaging Het
Trank1 C T 9: 111,181,144 (GRCm39) Q389* probably null Het
Vmn1r33 G T 6: 66,588,911 (GRCm39) S214R probably benign Het
Vmn2r25 A T 6: 123,800,581 (GRCm39) L587* probably null Het
Vps35l T C 7: 118,353,147 (GRCm39) I238T probably damaging Het
Zfp335 G A 2: 164,749,620 (GRCm39) T259I probably damaging 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
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
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
Predicted Primers PCR Primer
(F):5'- GGCTACATGGTGAGATCCCATC -3'
(R):5'- ACAAGCTGCTGATCCAGGTC -3'

Sequencing Primer
(F):5'- CCCAGCAATAAGTTGATGC -3'
(R):5'- GGTTATAGGCACGTACCATCATGC -3'
Posted On 2020-01-23