Browse CFLAR

Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location -
Domain PF01335 Death effector domain
Function

Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity.

> Gene Ontology
 
Biological Process GO:0000768 syncytium formation by plasma membrane fusion
GO:0003012 muscle system process
GO:0006949 syncytium formation
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007517 muscle organ development
GO:0007519 skeletal muscle tissue development
GO:0007520 myoblast fusion
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0010830 regulation of myotube differentiation
GO:0010832 negative regulation of myotube differentiation
GO:0010927 cellular component assembly involved in morphogenesis
GO:0010939 regulation of necrotic cell death
GO:0014706 striated muscle tissue development
GO:0014732 skeletal muscle atrophy
GO:0014841 skeletal muscle satellite cell proliferation
GO:0014842 regulation of skeletal muscle satellite cell proliferation
GO:0014855 striated muscle cell proliferation
GO:0014856 skeletal muscle cell proliferation
GO:0014857 regulation of skeletal muscle cell proliferation
GO:0014866 skeletal myofibril assembly
GO:0014888 striated muscle adaptation
GO:0014889 muscle atrophy
GO:0014891 striated muscle atrophy
GO:0014902 myotube differentiation
GO:0030239 myofibril assembly
GO:0031032 actomyosin structure organization
GO:0031099 regeneration
GO:0033002 muscle cell proliferation
GO:0034242 negative regulation of syncytium formation by plasma membrane fusion
GO:0042246 tissue regeneration
GO:0042692 muscle cell differentiation
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043403 skeletal muscle tissue regeneration
GO:0043500 muscle adaptation
GO:0043501 skeletal muscle adaptation
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051146 striated muscle cell differentiation
GO:0051147 regulation of muscle cell differentiation
GO:0051148 negative regulation of muscle cell differentiation
GO:0051153 regulation of striated muscle cell differentiation
GO:0051154 negative regulation of striated muscle cell differentiation
GO:0055001 muscle cell development
GO:0055002 striated muscle cell development
GO:0060142 regulation of syncytium formation by plasma membrane fusion
GO:0060537 muscle tissue development
GO:0060538 skeletal muscle organ development
GO:0060544 regulation of necroptotic process
GO:0070265 necrotic cell death
GO:0070266 necroptotic process
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097194 execution phase of apoptosis
GO:0097300 programmed necrotic cell death
GO:1901739 regulation of myoblast fusion
GO:1901740 negative regulation of myoblast fusion
GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:2001233 regulation of apoptotic signaling pathway
GO:2001234 negative regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
Molecular Function GO:0002020 protease binding
GO:0004175 endopeptidase activity
GO:0004197 cysteine-type endopeptidase activity
GO:0005123 death receptor binding
GO:0005126 cytokine receptor binding
GO:0008047 enzyme activator activity
GO:0008234 cysteine-type peptidase activity
GO:0032813 tumor necrosis factor receptor superfamily binding
GO:0097153 cysteine-type endopeptidase activity involved in apoptotic process
GO:0097200 cysteine-type endopeptidase activity involved in execution phase of apoptosis
Cellular Component GO:0031264 death-inducing signaling complex
GO:0031265 CD95 death-inducing signaling complex
GO:0044445 cytosolic part
GO:0045121 membrane raft
GO:0097342 ripoptosome
GO:0098589 membrane region
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG hsa04064 NF-kappa B signaling pathway
hsa04140 Regulation of autophagy
hsa04210 Apoptosis
hsa04668 TNF signaling pathway
Reactome R-HSA-109581: Apoptosis
R-HSA-5218900: CASP8 activity is inhibited
R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-73887: Death Receptor Signalling
R-HSA-69416: Dimerization of procaspase-8
R-HSA-140534: Ligand-dependent caspase activation
R-HSA-5357801: Programmed Cell Death
R-HSA-5213460: RIPK1-mediated regulated necrosis
R-HSA-5218859: Regulated Necrosis
R-HSA-3371378: Regulation by c-FLIP
R-HSA-5675482: Regulation of necroptotic cell death
R-HSA-162582: Signal Transduction
R-HSA-75158: TRAIL signaling
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CFLAR and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CFLAR and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28494239Endemic Burkitt LymphomaInhibit immunityOur systematic approach uncovered key mechanisms by which EBV oncoproteins activate the PI3K/AKT pathway and evade tumor suppressor responses. LMP1-induced cFLIP was found to be critical for LCL defense against TNFα-mediated programmed cell death, whereas EBV-induced BATF/IRF4 were critical for BIM suppression and MYC induction in LCLs.
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CFLAR in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.98; FDR: 0.02000 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CFLAR in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1140.635
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.3160.873
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0290.983
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1430.625
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3920.872
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1740.956
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0580.893
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.1030.954
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0110.996
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3490.861
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9180.758
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1180.0884
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CFLAR in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277311.1011.10.0181
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.1011.10.0286
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CFLAR. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CFLAR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CFLAR.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CFLAR. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CFLAR expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CFLAR and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCFLAR
NameCASP8 and FADD-like apoptosis regulator
Aliases CASH; Casper; CLARP; FLAME; FLIP; I-FLICE; MRIT; c-FLIP; CASP8AP1; FLAME-1; FLAME1; c-FLIPL; c-FLIPR; c-FLIP ......
Chromosomal Location2q33-q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CFLAR collected from DrugBank database.
> Drugs from DrugBank database
 

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