Incidental Mutation 'R5377:Mlkl'
ID 425619
Institutional Source Beutler Lab
Gene Symbol Mlkl
Ensembl Gene ENSMUSG00000012519
Gene Name mixed lineage kinase domain-like
Synonyms 9130019I15Rik
MMRRC Submission 042845-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.087) question?
Stock # R5377 (G1)
Quality Score 225
Status Not validated
Chromosome 8
Chromosomal Location 112038429-112064809 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 112054569 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Aspartic acid at position 189 (E189D)
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: E189D

PolyPhen 2 Score 0.231 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000055521
Gene: ENSMUSG00000012519
AA Change: E189D

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: E189D

PolyPhen 2 Score 0.231 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000113718
Gene: ENSMUSG00000012519
AA Change: E189D

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
SMART Domains Protein: ENSMUSP00000114701
Gene: ENSMUSG00000012519

DomainStartEndE-ValueType
PDB:4BTF|A 9 176 1e-114 PDB
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.5%
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: 62 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2m G T 6: 121,622,212 (GRCm39) V372F probably benign Het
Adcy10 G A 1: 165,347,464 (GRCm39) C393Y probably damaging Het
Adgrg7 A C 16: 56,550,669 (GRCm39) I681S possibly damaging Het
Akap8l T C 17: 32,540,485 (GRCm39) probably benign Het
Akr1a1 A T 4: 116,497,092 (GRCm39) V156E probably damaging Het
Alk T G 17: 72,202,734 (GRCm39) D1167A probably damaging Het
Ankrd11 T C 8: 123,620,453 (GRCm39) probably null Het
Aspm T A 1: 139,385,221 (GRCm39) N288K probably damaging Het
Aspm A G 1: 139,398,133 (GRCm39) probably null Het
Asxl2 G A 12: 3,524,618 (GRCm39) probably null Het
Atp6v0a1 A G 11: 100,946,413 (GRCm39) H802R probably damaging Het
B4galnt1 A G 10: 127,007,691 (GRCm39) T531A possibly damaging Het
Cecr2 A G 6: 120,733,530 (GRCm39) N506D possibly damaging Het
Crebrf T C 17: 26,978,839 (GRCm39) V509A probably damaging Het
Cyp4f40 A T 17: 32,894,590 (GRCm39) I413F probably null Het
Defb12 C A 8: 19,164,342 (GRCm39) probably null Het
Dnah2 T C 11: 69,312,674 (GRCm39) E4297G probably damaging Het
Dpysl5 A T 5: 30,948,857 (GRCm39) N371Y probably damaging Het
Eef1d G T 15: 75,775,038 (GRCm39) T207N probably benign Het
Esrrb C T 12: 86,565,783 (GRCm39) Q416* probably null Het
Exd2 T C 12: 80,536,222 (GRCm39) L284P probably damaging Het
Fat3 T A 9: 16,287,739 (GRCm39) I595F probably benign Het
Gm9920 A G 15: 54,972,371 (GRCm39) probably benign Het
Hephl1 T C 9: 14,981,084 (GRCm39) K783E probably damaging Het
Irs2 A G 8: 11,055,277 (GRCm39) S1052P probably benign Het
Kctd18 T C 1: 58,002,252 (GRCm39) I192V probably benign Het
Lama3 A G 18: 12,586,803 (GRCm39) D722G probably damaging Het
Lepr T C 4: 101,672,216 (GRCm39) V1080A possibly damaging Het
Lpin1 C T 12: 16,613,656 (GRCm39) G504S probably damaging Het
Lrit2 A C 14: 36,791,140 (GRCm39) Q273P possibly damaging Het
Mttp C T 3: 137,810,790 (GRCm39) R608H probably benign Het
Nav2 T C 7: 49,238,908 (GRCm39) V2011A probably benign Het
Nos2 A T 11: 78,848,317 (GRCm39) I1075F probably benign Het
Npat A G 9: 53,461,336 (GRCm39) probably null Het
Nucks1 T C 1: 131,846,771 (GRCm39) F16L probably damaging Het
Nus1 T C 10: 52,305,309 (GRCm39) S150P possibly damaging Het
Odad1 C T 7: 45,591,506 (GRCm39) R257* probably null Het
Oga A T 19: 45,746,461 (GRCm39) Y779* probably null Het
Or4c123 G T 2: 89,127,506 (GRCm39) T36K probably damaging Het
Or8b35 A T 9: 37,903,908 (GRCm39) Y40F probably benign Het
Pclo A G 5: 14,731,367 (GRCm39) T3290A unknown Het
Pign A T 1: 105,585,537 (GRCm39) F4Y probably benign Het
Rfx4 A G 10: 84,696,406 (GRCm39) N233D possibly damaging Het
Rpgrip1 A T 14: 52,397,652 (GRCm39) M1325L possibly damaging Het
Rufy4 T C 1: 74,186,822 (GRCm39) C537R probably damaging Het
Scaf11 T A 15: 96,315,001 (GRCm39) H1227L possibly damaging Het
Sec31b G T 19: 44,507,076 (GRCm39) P840T probably damaging Het
Slc16a9 T A 10: 70,118,958 (GRCm39) L426I probably damaging Het
Slc22a30 G A 19: 8,321,757 (GRCm39) Q436* probably null Het
Slc34a1 T C 13: 23,996,575 (GRCm39) S27P probably damaging Het
Tacc1 A G 8: 25,672,299 (GRCm39) S310P possibly damaging Het
Tmem245 G A 4: 56,947,084 (GRCm39) R110C probably damaging Het
Trip12 T C 1: 84,735,152 (GRCm39) Y953C probably damaging Het
Trpm7 C A 2: 126,684,775 (GRCm39) probably null Het
Ush2a G A 1: 188,644,320 (GRCm39) V4561I probably benign Het
Vmn1r192 C T 13: 22,371,801 (GRCm39) V140I probably benign Het
Vmn2r66 A T 7: 84,656,026 (GRCm39) I330N probably damaging Het
Vmn2r99 T C 17: 19,599,531 (GRCm39) V405A probably damaging Het
Wdhd1 A C 14: 47,509,678 (GRCm39) V172G probably benign Het
Zfhx3 C T 8: 109,677,817 (GRCm39) R2956C possibly damaging Het
Zfp446 T C 7: 12,716,178 (GRCm39) L283P possibly damaging Het
Zfp82 T C 7: 29,756,591 (GRCm39) K164E 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
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
Predicted Primers PCR Primer
(F):5'- TTAACCCTTTAGAGCCTGACAC -3'
(R):5'- TGAGAAGCTGTAGCCAGGAC -3'

Sequencing Primer
(F):5'- TTTAGAGCCTGACACCCTCAC -3'
(R):5'- TGTAGCCAGGACCAGGTCTG -3'
Posted On 2016-08-04