Incidental Mutation 'R8036:Mlkl'
ID 618250
Institutional Source Beutler Lab
Gene Symbol Mlkl
Ensembl Gene ENSMUSG00000012519
Gene Name mixed lineage kinase domain-like
Synonyms 9130019I15Rik
MMRRC Submission 067473-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.087) question?
Stock # R8036 (G1)
Quality Score 225.009
Status Validated
Chromosome 8
Chromosomal Location 112038429-112064809 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 112060086 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Glutamic Acid at position 100 (V100E)
Ref Sequence ENSEMBL: ENSMUSP00000055521 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000056157] [ENSMUST00000120432] [ENSMUST00000145862]
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 damaging
Transcript: ENSMUST00000056157
AA Change: V100E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: V100E

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: V100E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: V100E

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 damaging
Transcript: ENSMUST00000145862
AA Change: V108E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000114701
Gene: ENSMUSG00000012519
AA Change: V108E

DomainStartEndE-ValueType
PDB:4BTF|A 9 176 1e-114 PDB
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 100% (53/53)
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: 54 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc3 A G 11: 94,236,818 (GRCm39) V1473A possibly damaging Het
Akap9 T A 5: 4,120,397 (GRCm39) C3604* probably null Het
Alas1 A G 9: 106,112,721 (GRCm39) I545T probably benign Het
Anpep A C 7: 79,491,646 (GRCm39) D118E probably benign Het
Arhgef17 A T 7: 100,579,062 (GRCm39) S629T probably damaging Het
Arid2 C T 15: 96,266,625 (GRCm39) R558C probably damaging Het
Camk2n1 A G 4: 138,184,056 (GRCm39) D65G probably damaging Het
Ccdc177 T C 12: 80,804,897 (GRCm39) N459S unknown Het
Cenpe ACTCTCT ACTCT 3: 134,945,609 (GRCm39) probably null Het
Crb1 T C 1: 139,165,122 (GRCm39) I1062V probably benign Het
Decr2 A G 17: 26,301,962 (GRCm39) L256P probably damaging Het
Dhx37 T C 5: 125,501,739 (GRCm39) M507V probably benign Het
Disp1 A G 1: 182,870,803 (GRCm39) I539T probably damaging Het
Dqx1 T A 6: 83,036,788 (GRCm39) V264E probably damaging Het
Enpp4 A G 17: 44,413,136 (GRCm39) S133P possibly damaging Het
Fam149a T C 8: 45,802,048 (GRCm39) T476A probably benign Het
Fam20b A G 1: 156,533,407 (GRCm39) W70R probably damaging Het
Fbxl13 T A 5: 21,728,566 (GRCm39) N508Y probably damaging Het
Fjx1 A G 2: 102,280,720 (GRCm39) L405P probably damaging Het
Fn1 G A 1: 71,629,310 (GRCm39) Q2399* probably null Het
Foxa2 G C 2: 147,885,909 (GRCm39) T308S probably benign Het
Gatad1 T C 5: 3,693,540 (GRCm39) R210G probably benign Het
Gm10521 A G 1: 171,723,752 (GRCm39) D21G unknown Het
Gstcd C T 3: 132,787,868 (GRCm39) V277M probably damaging Het
Herpud1 A G 8: 95,119,014 (GRCm39) E256G probably damaging Het
Idh2 TCCCAGG T 7: 79,748,079 (GRCm39) probably benign Het
Kctd13 A G 7: 126,528,414 (GRCm39) D63G possibly damaging Het
Lamp3 C A 16: 19,519,809 (GRCm39) D125Y probably damaging Het
Luzp2 A G 7: 54,724,823 (GRCm39) D128G probably damaging Het
Lyve1 A G 7: 110,458,649 (GRCm39) C105R probably damaging Het
Muc5b T C 7: 141,421,478 (GRCm39) S4323P possibly damaging Het
Myoz3 T G 18: 60,713,922 (GRCm39) probably null Het
Nlrp9c T A 7: 26,070,864 (GRCm39) N906Y possibly damaging Het
Odad1 A G 7: 45,592,276 (GRCm39) D352G probably benign Het
Or10x4 A G 1: 174,219,382 (GRCm39) H249R probably damaging Het
Or51f23 A T 7: 102,452,763 (GRCm39) H26L possibly damaging Het
Or8b49 T C 9: 38,506,186 (GRCm39) F223S probably benign Het
Or8w1 C T 2: 87,465,847 (GRCm39) M81I probably benign Het
Pcsk9 G A 4: 106,311,536 (GRCm39) H232Y possibly damaging Het
Plec A G 15: 76,063,380 (GRCm39) I2230T possibly damaging Het
Pou2f3 T A 9: 43,058,205 (GRCm39) T47S probably damaging Het
Rab8a A T 8: 72,928,439 (GRCm39) I106F probably damaging Het
Relch A T 1: 105,605,902 (GRCm39) I181F probably damaging Het
Ros1 A T 10: 52,041,439 (GRCm39) S295T probably benign Het
Sh3yl1 T A 12: 30,992,098 (GRCm39) N222K possibly damaging Het
Slc6a9 C T 4: 117,725,083 (GRCm39) A559V possibly damaging Het
Spata20 T G 11: 94,369,963 (GRCm39) I778L probably benign Het
Taar1 A T 10: 23,797,033 (GRCm39) T244S probably benign Het
Tmem229b C A 12: 79,011,862 (GRCm39) C23F probably damaging Het
Ttll4 A G 1: 74,718,389 (GRCm39) Y80C probably benign Het
Ube2m G A 7: 12,769,566 (GRCm39) T176I probably benign Het
Zfp790 G A 7: 29,528,346 (GRCm39) A344T possibly damaging Het
Zfp90 G A 8: 107,145,760 (GRCm39) V31M probably benign Het
Zswim4 C T 8: 84,949,918 (GRCm39) R659Q 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
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
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
Predicted Primers PCR Primer
(F):5'- ACCAAAGTGAAGCTAGGATGCTC -3'
(R):5'- TACAGCCTCTCCAGAGACTC -3'

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