The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. However, the encoded protein lacks caspase activity and appears to be itself cleaved into two peptides by caspase-8. Several transcript variants encoding different isoforms have been found for this gene, and partial evidence for several more variants exists. [provided by RefSe... See more...

Aliases for CFLAR Gene

Aliases for CFLAR Gene

  • CASP8 And FADD Like Apoptosis Regulator 2 3 5
  • CASP8 And FADD-Like Apoptosis Regulator 2 3 4
  • Caspase-Like Apoptosis Regulatory Protein 3 4
  • Cellular FLICE-Like Inhibitory Protein 3 4
  • FADD-Like Antiapoptotic Molecule 1 3 4
  • MACH-Related Inducer Of Toxicity 3 4
  • Caspase-Eight-Related Protein 3 4
  • Inhibitor Of FLICE 3 4
  • Caspase Homolog 3 4
  • CASP8AP1 3 4
  • FLAME-1 3 4
  • I-FLICE 3 4
  • Casper 3 4
  • C-FLIP 3 4
  • CLARP 3 4
  • CASH 3 4
  • MRIT 3 4
  • Testis Secretory Sperm-Binding Protein Li 233m 3
  • Caspase-Related Inducer Of Apoptosis 3
  • Usurpin Beta 3
  • C-FLIPL 3
  • C-FLIPR 3
  • C-FLIPS 3
  • Usurpin 4
  • FLAME1 3
  • FLAME 3
  • CFLIP 3
  • FLIP 3

External Ids for CFLAR Gene

Previous HGNC Symbols for CFLAR Gene

  • CASP8AP1

Previous GeneCards Identifiers for CFLAR Gene

  • GC02P200197
  • GC02P200705
  • GC02P201944
  • GC02P202183
  • GC02P201806
  • GC02P201689
  • GC02P201980
  • GC02P193832

Summaries for CFLAR Gene

Entrez Gene Summary for CFLAR Gene

  • The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. However, the encoded protein lacks caspase activity and appears to be itself cleaved into two peptides by caspase-8. Several transcript variants encoding different isoforms have been found for this gene, and partial evidence for several more variants exists. [provided by RefSeq, Feb 2011]

CIViC Summary for CFLAR Gene

GeneCards Summary for CFLAR Gene

CFLAR (CASP8 And FADD Like Apoptosis Regulator) is a Protein Coding gene. Diseases associated with CFLAR include Cerebral Arteriopathy, Autosomal Dominant, With Subcortical Infarcts And Leukoencephalopathy, Type 1 and Colon Adenocarcinoma. Among its related pathways are Apoptosis and survival Caspase cascade and CDK-mediated phosphorylation and removal of Cdc6. Gene Ontology (GO) annotations related to this gene include cysteine-type peptidase activity. An important paralog of this gene is CASP8.

UniProtKB/Swiss-Prot Summary for CFLAR Gene

  • 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 Wiki entry for CFLAR Gene

Additional gene information for CFLAR Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CFLAR Gene

Genomics for CFLAR Gene

GeneHancer (GH) Regulatory Elements for CFLAR Gene

Promoters and enhancers for CFLAR Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CFLAR on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CFLAR

Top Transcription factor binding sites by QIAGEN in the CFLAR gene promoter:
  • p53
  • STAT1
  • TBP

Genomic Locations for CFLAR Gene

Genomic Locations for CFLAR Gene
chr2:201,116,154-201,176,687
(GRCh38/hg38)
Size:
60,534 bases
Orientation:
Plus strand
chr2:201,980,827-202,041,410
(GRCh37/hg19)
Size:
60,584 bases
Orientation:
Plus strand

Genomic View for CFLAR Gene

Genes around CFLAR on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CFLAR Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CFLAR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CFLAR Gene

Proteins for CFLAR Gene

  • Protein details for CFLAR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15519-CFLAR_HUMAN
    Recommended name:
    CASP8 and FADD-like apoptosis regulator
    Protein Accession:
    O15519
    Secondary Accessions:
    • B4DJE0
    • B7Z9F9
    • O14673
    • O14674
    • O14675
    • O15137
    • O15138
    • O15356
    • O15510
    • O43618
    • O43619
    • O43620
    • O60458
    • O60459
    • Q53TS6
    • Q54AF1
    • Q96TE4
    • Q9UEW1

    Protein attributes for CFLAR Gene

    Size:
    480 amino acids
    Molecular mass:
    55344 Da
    Quaternary structure:
    • TNFRSF6 stimulation triggers recruitment to the death-inducing signaling complex (DISC) formed by TNFRSF6, FADD and CASP8 (PubMed:9880531). A proteolytic fragment (p43) stays associated with the DISC (PubMed:9880531). Also interacts with FADD, CASP8, CASP3, TRAF1, TRAF2 and Bcl-X(L) (in vitro) (PubMed:9326610, PubMed:9208847). Interacts with RIPK1 (By similarity) (PubMed:9326610, PubMed:9208847, PubMed:9880531).
    • (Microbial infection) Interacts with HBV protein X.
    Miscellaneous:
    • [Isoform 9]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Three dimensional structures from OCA and Proteopedia for CFLAR Gene

neXtProt entry for CFLAR Gene

Post-translational modifications for CFLAR Gene

  • Proteolytically processed by CASP8 generating subunit p43 and p12.
  • Ubiquitination at Lys192
  • Modification sites at PhosphoSitePlus

Antibody Products

No data available for DME Specific Peptides for CFLAR Gene

Domains & Families for CFLAR Gene

Gene Families for CFLAR Gene

Protein Domains for CFLAR Gene

Suggested Antigen Peptide Sequences for CFLAR Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ58399, highly similar to CASP8 and FADD-like apoptosis regulator (B4DJE0_HUMAN)
  • Usurpin (CFLAR_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O15519

UniProtKB/Swiss-Prot:

CFLAR_HUMAN :
  • The caspase domain lacks the active site residues involved in catalysis.
  • Belongs to the peptidase C14A family.
Domain:
  • The caspase domain lacks the active site residues involved in catalysis.
Family:
  • Belongs to the peptidase C14A family.
genes like me logo Genes that share domains with CFLAR: view

Function for CFLAR Gene

Molecular function for CFLAR Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction:
Repressed by IL2/interleukin-2 after TCR stimulation, during progression to the S phase of the cell cycle.
GENATLAS Biochemistry:
caspase eight related,predominantly expressed in skeletal muscle,pancreas,heart,activated by Fas ligand,interacting with FADD and promoting apoptosis

Phenotypes From GWAS Catalog for CFLAR Gene

Gene Ontology (GO) - Molecular Function for CFLAR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 9208847
GO:0004197 cysteine-type endopeptidase activity IEA --
GO:0005123 death receptor binding IEA --
GO:0005515 protein binding IPI,IEA 9208847
GO:0008047 enzyme activator activity IDA 9208847
genes like me logo Genes that share ontologies with CFLAR: view
genes like me logo Genes that share phenotypes with CFLAR: view

Animal Models for CFLAR Gene

MGI Knock Outs for CFLAR:

Animal Model Products

miRNA for CFLAR Gene

Clone Products

  • Addgene plasmids for CFLAR

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CFLAR Gene

Localization for CFLAR Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CFLAR gene
Compartment Confidence
plasma membrane 5
cytosol 5
nucleus 4
mitochondrion 3
extracellular 2
cytoskeleton 2
endoplasmic reticulum 2
endosome 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
  • Plasma membrane (3)
  • Nuclear bodies (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CFLAR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA,IDA 18073330
GO:0005829 cytosol TAS --
GO:0031264 death-inducing signaling complex IDA 21803845
GO:0031265 CD95 death-inducing signaling complex IEA --
GO:0045121 membrane raft IEA --
genes like me logo Genes that share ontologies with CFLAR: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for CFLAR Gene

Pathways & Interactions for CFLAR Gene

genes like me logo Genes that share pathways with CFLAR: view

Pathways by source for CFLAR Gene

8 Qiagen pathways for CFLAR Gene
  • all-trans-Retinoic Acid Mediated Apoptosis
  • Apoptosis through Death Receptors
  • Apoptotic Pathways in Synovial Fibroblasts
  • Cellular Apoptosis Pathway
  • Fas Signaling
1 Cell Signaling Technology pathway for CFLAR Gene
3 GeneTex pathways for CFLAR Gene

SIGNOR curated interactions for CFLAR Gene

Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for CFLAR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006915 apoptotic process IBA,IMP 21737330
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process IBA 21873635
GO:0007519 skeletal muscle tissue development ISS --
GO:0009617 response to bacterium IEA --
genes like me logo Genes that share ontologies with CFLAR: view

Drugs & Compounds for CFLAR Gene

(48) Drugs for CFLAR Gene - From: DGIdb and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Nintedanib Approved Pharma inhibitor VEGFR, FGFR, PDGFR, and FLT3 inhibitor, Kinase Inhibitors 141
Dovitinib Investigational Pharma Inhibition, inhibitor Multi-targeted RTK inhibitor, Kinase Inhibitors, Fibroblast growth factor receptor (FGFR)inhibitors 0
Idronoxil Investigational Pharma inhibitor Caspase activator, XIAP inhibitor, FLIP suppressor, and TOPO II inhibitor 0
Cometriq Pharma inhibitor, Biomarker RTK, HGFR, VEGFR2, KIT, Flt3, and Tie-2 inhibitor, cMET Inhibitors 0

(24) Additional Compounds for CFLAR Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CFLAR: view

Transcripts for CFLAR Gene

mRNA/cDNA for CFLAR Gene

15 REFSEQ mRNAs :
42 NCBI additional mRNA sequence :
25 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

  • Addgene plasmids for CFLAR

Alternative Splicing Database (ASD) splice patterns (SP) for CFLAR Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b · 6c · 6d · 6e · 6f ^ 7 ^ 8a · 8b · 8c · 8d · 8e ^ 9a · 9b · 9c · 9d ^ 10 ^ 11 ^
SP1: - - - - - - - - - - - -
SP2: - - - - - - - - -
SP3: - - - - -
SP4: - - - - -
SP5: - - - - -
SP6: - - - - - - - - - - - -
SP7: - - - - -
SP8: - -
SP9:
SP10: - - - - - - - - - - - -
SP11: - - - - -
SP12: - -
SP13:
SP14: - - -
SP15: - - - -
SP16: - -
SP17: - - - - - - - - - - - -
SP18: - - - - - - - - -
SP19: - - - - -
SP20: - - - - - - - - - - - - - -
SP21: - - - - - - - - -
SP22: - - -

ExUns: 12a · 12b · 12c ^ 13a · 13b · 13c ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^ 20a · 20b · 20c
SP1: - - - - - - -
SP2: - - - - - - -
SP3: - - - - - -
SP4: - - - - -
SP5: - - - - - - - - -
SP6: - - - - - - - - -
SP7: - - - - - - - - - -
SP8: - - - - - - -
SP9: - - - - - -
SP10: - -
SP11: - -
SP12: - - - - -
SP13: - - - - -
SP14:
SP15: -
SP16: - -
SP17:
SP18:
SP19:
SP20:
SP21:
SP22:

Relevant External Links for CFLAR Gene

GeneLoc Exon Structure for
CFLAR

Expression for CFLAR Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CFLAR Gene

mRNA differential expression in normal tissues according to GTEx for CFLAR Gene

This gene is overexpressed in Whole Blood (x7.0).

Protein differential expression in normal tissues from HIPED for CFLAR Gene

This gene is overexpressed in Plasma (66.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CFLAR Gene



Protein tissue co-expression partners for CFLAR Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CFLAR

SOURCE GeneReport for Unigene cluster for CFLAR Gene:

Hs.390736

mRNA Expression by UniProt/SwissProt for CFLAR Gene:

O15519-CFLAR_HUMAN
Tissue specificity: Widely expressed. Higher expression in skeletal muscle, pancreas, heart, kidney, placenta, and peripheral blood leukocytes. Also detected in diverse cell lines. Isoform 8 is predominantly expressed in testis and skeletal muscle.

Evidence on tissue expression from TISSUES for CFLAR Gene

  • Nervous system(4.8)
  • Blood(4.7)
  • Heart(4.6)
  • Kidney(4.5)
  • Skin(4.5)
  • Lung(4)
  • Intestine(3.1)
  • Spleen(2.9)
  • Liver(2.8)
  • Muscle(2.8)
  • Bone marrow(2.7)
  • Lymph node(2.7)
  • Pancreas(2.3)
  • Thyroid gland(2.3)
  • Stomach(2.1)
genes like me logo Genes that share expression patterns with CFLAR: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for CFLAR Gene

Orthologs for CFLAR Gene

This gene was present in the common ancestor of chordates.

Orthologs for CFLAR Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CFLAR 31 30
  • 99.79 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CFLAR 31 30
  • 83.47 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CFLAR 30
  • 82.25 (n)
FLIP 31
  • 74 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cflar 30
  • 76.3 (n)
mouse
(Mus musculus)
Mammalia Cflar 17 31 30
  • 75.72 (n)
Gm9845 31
  • 71 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia CFLAR 31
  • 52 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CFLAR 31
  • 49 (a)
OneToOne
chicken
(Gallus gallus)
Aves CFLAR 31 30
  • 57.94 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CFLAR 31
  • 44 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cflar 30
  • 49.96 (n)
zebrafish
(Danio rerio)
Actinopterygii cflara 31 30
  • 47.58 (n)
OneToMany
cflarb 31
  • 30 (a)
OneToMany
-- 30
Species where no ortholog for CFLAR was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CFLAR Gene

ENSEMBL:
Gene Tree for CFLAR (if available)
TreeFam:
Gene Tree for CFLAR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CFLAR: view image

Paralogs for CFLAR Gene

(38) SIMAP similar genes for CFLAR Gene using alignment to 11 proteins:

  • CFLAR_HUMAN
  • C9J408_HUMAN
  • C9J4Q0_HUMAN
  • C9JK38_HUMAN
  • C9JSU3_HUMAN
  • C9JV51_HUMAN
  • E9PAP3_HUMAN
  • F8WBH9_HUMAN
  • M0QY57_HUMAN
  • M0QYM0_HUMAN
  • M0R1A8_HUMAN
genes like me logo Genes that share paralogs with CFLAR: view

Variants for CFLAR Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CFLAR Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
773850 Benign: not provided 201,160,763(+) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
783347 Benign: not provided 201,145,378(+) C/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT
rs13424615 - p.Leu203Ile