Gene: MLKL

Basic information

Full name: mixed lineage kinase domain like pseudokinase
Ensembl: ENSG00000168404.13
Summary: This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to be inactive because it lacks several residues required for 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. Inhibitor studies and knockdown of this gene inhibited TNF-induced necrosis. High levels of this protein and RIP3 are associated with inflammatory bowel disease in children. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2015]
Annotation: Druggable target (Tier T4) Protein Kinase

Protein product

ENST00000308807.12 Primary ENSP00000308351.7 (6 phosphosites)
ENST00000306247.11

Phosphosites on the primary protein product

Tumor and normal comparison

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		Signed p-values
Data type	Meta P	BRCA	CCRCC	COAD	GBM	HNSCC	LSCC	LUAD	OV	PDAC	UCEC
RNA	0.22	-	6.9e-29	-	-	0.011	-3.6e-16	-4.1e-14	-	1.6e-6	-
protein	5.7e-49	-	2.1e-30	1.3e-26	-	3.7e-11	0.45	0.02	-0.062	1.6e-12	4.9e-6

* P-values are from Wilcoxon rank sum test and can be clicked to show the box plots. Positive values mean higher abundance in tumor. BRCA and GBM do not have normal samples.

mRNA expression at gene level

Protein expression

* Mild outlier: filled circle; Extreme outlier: empty circle.

Phenotype and mutation association

Manhattan plot summarizing associations of phenotypes and mutations across all cohorts and omics data types

* Data points of significant associations above and below the dotted lines can be hovered to show the phenotype.

Associations of the protein abundance of MLKL with phenotypes and mutations

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			Signed p-values
Phenotype		Meta P	BRCA	CCRCC	COAD	GBM	HNSCC	LSCC	LUAD	OV	PDAC	UCEC
	HALLMARK_INTERFERON_GAMMA_RESPONSE	1.7e-65	2.2e-16	0.084	0.089	2.2e-16	2.2e-16	2.2e-16	8.7e-6	2.0e-4	3e-7	6.7e-6
	HALLMARK_IL6_JAK_STAT3_SIGNALING	3.5e-65	2.2e-16	0.069	0.013	2.2e-16	2.2e-16	2.2e-16	2.0e-5	2.2e-5	4.1e-7	1.4e-3
	HALLMARK_ALLOGRAFT_REJECTION	1.2e-61	2.2e-16	0.16	0.15	2.2e-16	2.2e-16	2.2e-16	2.0e-5	5.6e-6	1.9e-5	2.9e-4
	ESTIMATE: ImmuneScore	1.3e-59	2.2e-16	0.1	0.19	2.2e-16	2.2e-16	2.2e-16	1.8e-4	2.1e-6	3.0e-4	2.9e-4
	HALLMARK_COMPLEMENT	3.9e-58	2.2e-16	0.4	0.096	2.2e-16	4.2e-12	2.2e-16	8.6e-6	3.8e-7	4.1e-4	2.1e-4
	HALLMARK_INFLAMMATORY_RESPONSE	3.9e-57	2.2e-16	0.055	0.11	2.2e-16	1.3e-10	2.2e-16	1.8e-4	1.3e-6	4.5e-5	1.8e-3
	xcell: immune score	2e-55	2.2e-16	0.099	0.24	2.2e-16	2.2e-16	2.2e-16	8.6e-3	3.2e-5	2.4e-4	5.0e-4
	HALLMARK_IL2_STAT5_SIGNALING	1.4e-52	2.2e-16	0.077	0.48	2.2e-16	3.8e-9	2.2e-16	4.7e-5	2.4e-7	5.1e-3	1.2e-3
	HALLMARK_INTERFERON_ALPHA_RESPONSE	2.1e-51	2.2e-16	0.12	0.077	4.4e-8	1.1e-8	2.2e-16	7.6e-5	1.2e-3	1.1e-6	3.1e-6
	PROGENy: NFkB	1.4e-47	2.2e-16	0.021	0.026	2.2e-16	1.2e-3	2.4e-11	1.2e-4	2.2e-4	4.3e-7	0.018

Showing 1 to 10 of 256 rows

* P-values could be from test for Spearman correlation, Wilcoxon rank sum test, Jonckheere-Terpstra trend test or Cox regression depending on the data type. P-values for individual cohorts can be clicked to show the data plots. The matrix icons in each row can be clicked to show a heatmap summary of associations across all cohorts and omics. The rows in the table can be expanded to show results from other omics.

PERT-P100-PRM_DMSO
PERT-P100-PRM_VORINOSTAT
PERT-PSP_ANTI_CD3
PERT-PSP_EGF
PERT-PSP_IGF_1
PERT-PSP_INSULIN
PERT-PSP_NOCODAZOLE
PERT-PSP_UV
Clinical: BMI
Clinical: progression_free_survival
chromosomal instability
cibersort: T cell regulatory (Tregs)
cibersort: Monocyte
cibersort: Macrophage M0
cibersort: Macrophage M1
cibersort: Macrophage M2
cibersort: Myeloid dendritic cell activated
cibersort: Mast cell activated
cibersort: Mast cell resting
cibersort: Neutrophil
xcell: Myeloid dendritic cell activated
xcell: B cell
xcell: T cell CD4+ (non-regulatory)
xcell: T cell CD4+ central memory
xcell: T cell CD4+ effector memory
xcell: T cell CD8+ effector memory
xcell: Myeloid dendritic cell
xcell: Endothelial cell
xcell: Cancer associated fibroblast
xcell: Macrophage M1
xcell: Macrophage M2
xcell: B cell naive
xcell: Neutrophil
xcell: NK cell
xcell: T cell gamma delta
xcell: T cell CD4+ Th2
xcell: T cell regulatory (Tregs)
xcell: immune score
xcell: stroma score
xcell: microenvironment score
ESTIMATE: ImmuneScore
PROGENy: EGFR
PROGENy: Estrogen
PROGENy: JAK-STAT
PROGENy: NFkB
PROGENy: TGFb
PROGENy: TNFa
PROGENy: VEGF
PROGENy: WNT
HALLMARK_TNFA_SIGNALING_VIA_NFKB
HALLMARK_CHOLESTEROL_HOMEOSTASIS
HALLMARK_MITOTIC_SPINDLE
HALLMARK_WNT_BETA_CATENIN_SIGNALING
HALLMARK_G2M_CHECKPOINT
HALLMARK_NOTCH_SIGNALING
HALLMARK_ADIPOGENESIS
HALLMARK_ESTROGEN_RESPONSE_EARLY
HALLMARK_ESTROGEN_RESPONSE_LATE
HALLMARK_MYOGENESIS
HALLMARK_PROTEIN_SECRETION
HALLMARK_INTERFERON_GAMMA_RESPONSE
HALLMARK_APICAL_JUNCTION
HALLMARK_PI3K_AKT_MTOR_SIGNALING
HALLMARK_MTORC1_SIGNALING
HALLMARK_MYC_TARGETS_V1
HALLMARK_MYC_TARGETS_V2
HALLMARK_XENOBIOTIC_METABOLISM
HALLMARK_FATTY_ACID_METABOLISM
HALLMARK_OXIDATIVE_PHOSPHORYLATION
HALLMARK_P53_PATHWAY
HALLMARK_UV_RESPONSE_UP
HALLMARK_UV_RESPONSE_DN
HALLMARK_IL2_STAT5_SIGNALING
HALLMARK_BILE_ACID_METABOLISM
HALLMARK_KRAS_SIGNALING_UP
HALLMARK_KRAS_SIGNALING_DN
DISEASE-PSP_Alzheimer's_disease
KINASE-PSP_Akt1/AKT1
KINASE-PSP_AMPKA1/PRKAA1
KINASE-PSP_AurB/AURKB
KINASE-PSP_CDK5
KINASE-PSP_ERK1/MAPK3
KINASE-PSP_ERK2/MAPK1
KINASE-PSP_GSK3B
KINASE-PSP_JNK1/MAPK8
KINASE-PSP_MAPKAPK2
KINASE-PSP_P38A/MAPK14
KINASE-PSP_p90RSK/RPS6KA1
KINASE-PSP_PAK1
KINASE-PSP_PKACA/PRKACA
PATH-NP_PROLACTIN_PATHWAY
PATH-NP_TIE2_PATHWAY
PATH-NP_TSLP_PATHWAY
PATH-WP_PI3K-Akt_Signaling_Pathway
PERT-P100-DIA_EPZ-5687
PERT-P100-DIA_SEMAGACESTAT
PERT-P100-DIA_STAUROSPORINE
PERT-P100-DIA_VORINOSTAT
PERT-PSP_SII_ANGIOTENSIN_2
Clinical: Sex
Clinical: Age
Clinical: Path_Stage_pN
Clinical: Stage
Clinical: Tumor_Size_cm
Clinical: Path_Stage_pT
Clinical: Histologic_Grade
Clinical: Tobacco_smoking_history
Clinical: Tumor_necrosis
Clinical: overall_survival
mutation burden
cibersort: B cell naive
cibersort: B cell memory
cibersort: B cell plasma
cibersort: T cell CD8+
cibersort: T cell CD4+ naive
cibersort: T cell CD4+ memory resting
cibersort: T cell CD4+ memory activated
cibersort: T cell follicular helper
cibersort: T cell gamma delta
cibersort: NK cell resting
cibersort: NK cell activated
cibersort: Myeloid dendritic cell resting
cibersort: Eosinophil
xcell: T cell CD4+ memory
xcell: T cell CD4+ naive
xcell: T cell CD8+ naive
xcell: T cell CD8+
xcell: T cell CD8+ central memory
xcell: Class-switched memory B cell
xcell: Common lymphoid progenitor
xcell: Common myeloid progenitor
xcell: Eosinophil
xcell: Granulocyte-monocyte progenitor
xcell: Hematopoietic stem cell
xcell: Macrophage
xcell: Mast cell
xcell: B cell memory
xcell: Monocyte
xcell: T cell NK
xcell: Plasmacytoid dendritic cell
xcell: B cell plasma
xcell: T cell CD4+ Th1
ESTIMATE: StromalScore
ESTIMATE: ESTIMATEScore
PROGENy: Androgen
PROGENy: Hypoxia
PROGENy: MAPK
PROGENy: p53
PROGENy: PI3K
PROGENy: Trail
HALLMARK_HYPOXIA
HALLMARK_TGF_BETA_SIGNALING
HALLMARK_IL6_JAK_STAT3_SIGNALING
HALLMARK_DNA_REPAIR
HALLMARK_APOPTOSIS
HALLMARK_ANDROGEN_RESPONSE
HALLMARK_INTERFERON_ALPHA_RESPONSE
HALLMARK_APICAL_SURFACE
HALLMARK_HEDGEHOG_SIGNALING
HALLMARK_COMPLEMENT
HALLMARK_UNFOLDED_PROTEIN_RESPONSE
HALLMARK_E2F_TARGETS
HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION
HALLMARK_INFLAMMATORY_RESPONSE
HALLMARK_GLYCOLYSIS
HALLMARK_REACTIVE_OXYGEN_SPECIES_PATHWAY
HALLMARK_ANGIOGENESIS
HALLMARK_HEME_METABOLISM
HALLMARK_COAGULATION
HALLMARK_PEROXISOME
HALLMARK_ALLOGRAFT_REJECTION
HALLMARK_SPERMATOGENESIS
HALLMARK_PANCREAS_BETA_CELLS
KINASE-PSP_CAMK2A
KINASE-PSP_CDK1
KINASE-PSP_CDK2
KINASE-PSP_Chk1/CHEK1
KINASE-PSP_CK2A1/CSNK2A1
KINASE-PSP_mTOR/MTOR
KINASE-PSP_PKCA/PRKCA
KINASE-PSP_PKCD/PRKCD
KINASE-PSP_PLK1
KINASE-PSP_PRKD1
KINASE-PSP_RSK2/RPS6KA3
PATH-NP_EGFR1_PATHWAY
PATH-NP_IL33_PATHWAY
PATH-NP_LEPTIN_PATHWAY
PERT-PSP_PHORBOL_ESTER
SBS1 (clock-like)
SBS10a (POLE mutation)
SBS10b (POLE mutation)
SBS13 (APOBEC activity)
SBS14 (POLE mutation and defective DNA mismatch repair)
SBS15 (defective DNA mismatch repair)
SBS2 (APOBEC activity)
SBS20 (POLD1 mutation and defective DNA mismatch repair)
SBS24 (aflatoxin exposure)
SBS26 (defective DNA mismatch repair)
SBS28 (unknown)
SBS3 (HRD)
SBS31 (platinum chemotherapy)
SBS4 (smoking)
SBS40 (unknown)
SBS42 (haloalkane exposure)
SBS44 (defective DNA mismatch repair)
SBS5 (unknown)
SBS6 (defective DNA mismatch repair)
SBS7a (UVR)
SBS7b (UVR)
TP53 mutation
KRAS mutation
PTEN mutation
CDKN2A mutation
PIK3CA mutation
RNF43 mutation
ARID1A mutation
CASP8 mutation
EGFR mutation
PIK3R1 mutation
RPL22 mutation
SETD1B mutation
UPF3A mutation
ACVR2A mutation
ANO10 mutation
APC mutation
ATRX mutation
B2M mutation
BAP1 mutation
BMPR2 mutation
CTCF mutation
CTNNB1 mutation
ESRP1 mutation
FAT1 mutation
GATA3 mutation
INPPL1 mutation
KDM5C mutation
KEAP1 mutation
LMAN1 mutation
MAP3K1 mutation
MXRA8 mutation
NOTCH1 mutation
PBRM1 mutation
PTX4 mutation
RB1 mutation
SETD2 mutation
SLC3A2 mutation
SMAD4 mutation
SOX9 mutation
STK11 mutation
TBC1D23 mutation
TCF7L2 mutation
VHL mutation
ZFP36L2 mutation
ZNF540 mutation
Tumor Purity (WGS)
Tumor Purity (ABSOLUTE)

Cis-association

Associations between omics data of MLKL

* The numbers are Spearman correlation coefficients and can be clicked to show the scatter plots. The color and size of the circles correlate with the coefficients.

Trans-association

Associations of the protein abundance of MLKL and the protein abundance of other genes

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			Signed p-values
Gene		Meta P	BRCA	CCRCC	COAD	GBM	HNSCC	LSCC	LUAD	OV	PDAC	UCEC
No matching records found

* P-values are from test for Spearman correlation. P-values for individual cohorts can be clicked to show the data plots. The matrix icons in each row can be clicked to show a heatmap summary of associations across all cohorts and omics. The rows in the table can be expanded to show results from other omics.

Gene set enrichment analysis

Submit genes and the common logarithm of the p-values of their association with to WebGestalt.

Gene: MLKL

Basic information

Protein product

Phosphosites on the primary protein product

Tumor and normal comparison

mRNA expression at gene level

Protein expression

Phenotype and mutation association

Phenotype List

Cis-association

Trans-association

Gene set enrichment analysis