Human Gene CFLAR (ENST00000309955.8_7) from GENCODE V47lift37
  Description: CASP8 and FADD like apoptosis regulator, transcript variant 26 (from RefSeq NR_147251.2)
Gencode Transcript: ENST00000309955.8_7
Gencode Gene: ENSG00000003402.21_13
Transcript (Including UTRs)
   Position: hg19 chr2:201,980,887-202,041,410 Size: 60,524 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg19 chr2:201,994,589-202,028,696 Size: 34,108 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:201,980,887-202,041,410)mRNA (may differ from genome)Protein (480 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: CFLAR_HUMAN
DESCRIPTION: RecName: Full=CASP8 and FADD-like apoptosis regulator; AltName: Full=Caspase homolog; Short=CASH; AltName: Full=Caspase-eight-related protein; Short=Casper; AltName: Full=Caspase-like apoptosis regulatory protein; Short=CLARP; AltName: Full=Cellular FLICE-like inhibitory protein; Short=c-FLIP; AltName: Full=FADD-like antiapoptotic molecule 1; Short=FLAME-1; AltName: Full=Inhibitor of FLICE; Short=I-FLICE; AltName: Full=MACH-related inducer of toxicity; Short=MRIT; AltName: Full=Usurpin; Contains: RecName: Full=CASP8 and FADD-like apoptosis regulator subunit p43; Contains: RecName: Full=CASP8 and FADD-like apoptosis regulator subunit p12; Flags: Precursor;
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.
SUBUNIT: TNFRSF6 stimulation triggers recruitment to the death- inducing signaling complex (DISC) formed by TNFRSF6, FADD and caspase-8. A proteolytic fragment (p43) stays associated with the DISC. Also interacts with caspase-10, caspase-3, TRAF1, TRAF2 and Bcl-X(L) (in vitro). Interacts with HBV protein X.
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.
INDUCTION: Repressed by IL2/interleukin-2 after TCR stimulation, during progression to the S phase of the cell cycle.
DOMAIN: The caspase domain lacks the active sites residues involved in catalysis.
PTM: Proteolytically processed; probably by caspase-8. Processing likely occurs at the DISC and generates subunit p43 and p12.
SIMILARITY: Belongs to the peptidase C14A family.
SIMILARITY: Contains 2 DED (death effector) domains.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CFLARID40065ch2q33.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: CFLAR
Diseases sorted by gene-association score: cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 (8), choroid plexus papilloma (7), actinic keratosis (5), juvenile amyotrophic lateral sclerosis (5), alopecia, androgenetic, 1 (4), malignant glioma (4), colorectal cancer (2), prostate cancer (2), lung cancer (2), chronic lymphocytic leukemia (2), lymphoma, non-hodgkin (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 27.65 RPKM in Whole Blood
Total median expression: 500.34 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -173.30455-0.381 Picture PostScript Text
3' UTR -4465.1312714-0.351 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011029 - DEATH-like
IPR001875 - DED
IPR011600 - Pept_C14_cat
IPR001309 - Pept_C14_ICE_p20
IPR002398 - Pept_C14_p45
IPR015917 - Pept_C14_p45_core

Pfam Domains:
PF00656 - Caspase domain
PF01335 - Death effector domain

SCOP Domains:
47986 - DEATH domain
52129 - Caspase-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3H11 - X-ray MuPIT 3H13 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O15519
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002020 protease binding
GO:0004197 cysteine-type endopeptidase activity
GO:0005123 death receptor binding
GO:0005515 protein binding
GO:0008047 enzyme activator activity
GO:0008234 cysteine-type peptidase activity
GO:0016504 peptidase activator activity
GO:0044877 macromolecular complex binding
GO:0046982 protein heterodimerization activity
GO:0097200 cysteine-type endopeptidase activity involved in execution phase of apoptosis

Biological Process:
GO:0001666 response to hypoxia
GO:0006508 proteolysis
GO:0006915 apoptotic process
GO:0007519 skeletal muscle tissue development
GO:0010667 negative regulation of cardiac muscle cell apoptotic process
GO:0010952 positive regulation of peptidase activity
GO:0010976 positive regulation of neuron projection development
GO:0014732 skeletal muscle atrophy
GO:0014842 regulation of skeletal muscle satellite cell proliferation
GO:0014866 skeletal myofibril assembly
GO:0016032 viral process
GO:0032869 cellular response to insulin stimulus
GO:0033574 response to testosterone
GO:0042981 regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043085 positive regulation of catalytic activity
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043403 skeletal muscle tissue regeneration
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0060544 regulation of necroptotic process
GO:0060546 negative regulation of necroptotic process
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071364 cellular response to epidermal growth factor stimulus
GO:0071392 cellular response to estradiol stimulus
GO:0071456 cellular response to hypoxia
GO:0071549 cellular response to dexamethasone stimulus
GO:0071732 cellular response to nitric oxide
GO:0072126 positive regulation of glomerular mesangial cell proliferation
GO:0097194 execution phase of apoptosis
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:1903055 positive regulation of extracellular matrix organization
GO:1903427 negative regulation of reactive oxygen species biosynthetic process
GO:1903845 negative regulation of cellular response to transforming growth factor beta stimulus
GO:1903944 negative regulation of hepatocyte apoptotic process
GO:1904036 negative regulation of epithelial cell apoptotic process
GO:2000347 positive regulation of hepatocyte proliferation
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0031264 death-inducing signaling complex
GO:0031265 CD95 death-inducing signaling complex
GO:0045121 membrane raft
GO:0097342 ripoptosome


-  Descriptions from all associated GenBank mRNAs
  AK296036 - Homo sapiens cDNA FLJ58399 complete cds, highly similar to CASP8 and FADD-like apoptosis regulator precursor.
AK297387 - Homo sapiens cDNA FLJ56698 complete cds, highly similar to CASP8 and FADD-like apoptosis regulator precursor.
Y14040 - Homo sapiens mRNA for CASH beta protein.
Y14039 - Homo sapiens mRNA for CASH alpha protein.
AF005774 - Homo sapiens caspase-like apoptosis regulatory protein (clarp) mRNA, alternatively spliced, complete cds.
AF009616 - Homo sapiens FLAME-1 mRNA, complete cds.
AF010127 - Homo sapiens Casper mRNA, complete cds.
U97074 - Homo sapiens FLICE-like inhibitory protein long form mRNA, complete cds.
AK315924 - Homo sapiens cDNA, FLJ78823 complete cds, highly similar to CASP8 and FADD-like apoptosis regulator precursor.
BC001602 - Homo sapiens CASP8 and FADD-like apoptosis regulator, mRNA (cDNA clone MGC:2044 IMAGE:3542993), complete cds.
KR422625 - Homo sapiens cell line Caki-2 usurpin-beta splice variant (CFLAR) mRNA, complete cds, alternatively spliced.
AB209600 - Homo sapiens mRNA for CASP8 and FADD-like apoptosis regulator variant protein.
JD073045 - Sequence 54069 from Patent EP1572962.
JD518809 - Sequence 499833 from Patent EP1572962.
DQ596262 - Homo sapiens piRNA piR-34328, complete sequence.
JD361732 - Sequence 342756 from Patent EP1572962.
JD044269 - Sequence 25293 from Patent EP1572962.
JD339107 - Sequence 320131 from Patent EP1572962.
JD336734 - Sequence 317758 from Patent EP1572962.
AF015450 - Homo sapiens Usurpin-alpha mRNA, complete cds.
AK308767 - Homo sapiens cDNA, FLJ98808.
AK289913 - Homo sapiens cDNA FLJ78499 complete cds, highly similar to Homo sapiens CASP8 and FADD-like apoptosis regulator, mRNA.
AK315208 - Homo sapiens cDNA, FLJ96198, highly similar to Homo sapiens CASP8 and FADD-like apoptosis regulator (CFLAR), mRNA.
U97075 - Homo sapiens FLICE-like inhibitory protein short form mRNA, complete cds.
LF206105 - JP 2014500723-A/13608: Polycomb-Associated Non-Coding RNAs.
JD174531 - Sequence 155555 from Patent EP1572962.
JD400195 - Sequence 381219 from Patent EP1572962.
LF351463 - JP 2014500723-A/158966: Polycomb-Associated Non-Coding RNAs.
AF041458 - Homo sapiens I-FLICE mRNA, complete cds.
HM005351 - Homo sapiens clone HTL-T-38 testis secretory sperm-binding protein Li 233m mRNA, complete cds.
AF005775 - Homo sapiens caspase-like apoptosis regulatory protein 2 (clarp) mRNA, alternatively spliced, complete cds.
AF015452 - Homo sapiens Usurpin-gamma mRNA, complete cds.
CU674780 - Synthetic construct Homo sapiens gateway clone IMAGE:100020300 5' read CFLAR mRNA.
AF015451 - Homo sapiens Usurpin-beta mRNA, complete cds.
AF041460 - Homo sapiens I-FLICE isoform 3 mRNA, complete cds.
AB590361 - Synthetic construct DNA, clone: pFN21AE1312, Homo sapiens CFLAR gene for CASP8 and FADD-like apoptosis regulator, without stop codon, in Flexi system.
DQ893760 - Synthetic construct Homo sapiens clone IMAGE:100008220; FLH164286.01L; RZPDo839E09161D CASP8 and FADD-like apoptosis regulator (CFLAR) gene, encodes complete protein.
BT006751 - Homo sapiens CASP8 and FADD-like apoptosis regulator mRNA, complete cds.
DQ890592 - Synthetic construct clone IMAGE:100003222; FLH164290.01X; RZPDo839E09162D CASP8 and FADD-like apoptosis regulator (CFLAR) gene, encodes complete protein.
KJ892636 - Synthetic construct Homo sapiens clone ccsbBroadEn_02030 CFLAR gene, encodes complete protein.
AF009617 - Homo sapiens FLAME-1-beta mRNA, alternatively spliced, complete cds.
AF009618 - Homo sapiens FLAME-1-gamma mRNA, alternatively spliced, complete cds.
AF009619 - Homo sapiens FLAME-1-delta mRNA, alternatively spliced, complete cds.
U85059 - Human protease MRIT-alpha-1 mRNA, complete cds.
AX751991 - Sequence 1 from Patent WO03035868.
AF041461 - Homo sapiens I-FLICE isoform 4 mRNA, complete cds.
LF351462 - JP 2014500723-A/158965: Polycomb-Associated Non-Coding RNAs.
LF351461 - JP 2014500723-A/158964: Polycomb-Associated Non-Coding RNAs.
JD025931 - Sequence 6955 from Patent EP1572962.
JD022408 - Sequence 3432 from Patent EP1572962.
AK304585 - Homo sapiens cDNA FLJ59611 complete cds, highly similar to CASP8 and FADD-like apoptosis regulator precursor.
JD033854 - Sequence 14878 from Patent EP1572962.
AF041462 - Homo sapiens I-FLICE isoform 5 mRNA, complete cds.
JD032568 - Sequence 13592 from Patent EP1572962.
JD030588 - Sequence 11612 from Patent EP1572962.
LF351460 - JP 2014500723-A/158963: Polycomb-Associated Non-Coding RNAs.
AF041459 - Homo sapiens I-FLICE isoform 2 mRNA, complete cds.
AX751993 - Sequence 3 from Patent WO03035868.
CQ967473 - Sequence 15 from Patent EP1486564.
JD084122 - Sequence 65146 from Patent EP1572962.
JD101874 - Sequence 82898 from Patent EP1572962.
JD167622 - Sequence 148646 from Patent EP1572962.
JD481204 - Sequence 462228 from Patent EP1572962.
JD361809 - Sequence 342833 from Patent EP1572962.
JD158876 - Sequence 139900 from Patent EP1572962.
JD266512 - Sequence 247536 from Patent EP1572962.
JD344084 - Sequence 325108 from Patent EP1572962.
JD178710 - Sequence 159734 from Patent EP1572962.
JD300548 - Sequence 281572 from Patent EP1572962.
JD411728 - Sequence 392752 from Patent EP1572962.
JD056621 - Sequence 37645 from Patent EP1572962.
JD137547 - Sequence 118571 from Patent EP1572962.
JD313680 - Sequence 294704 from Patent EP1572962.
JD349074 - Sequence 330098 from Patent EP1572962.
JD380262 - Sequence 361286 from Patent EP1572962.
JD277702 - Sequence 258726 from Patent EP1572962.
JD345682 - Sequence 326706 from Patent EP1572962.
JD225366 - Sequence 206390 from Patent EP1572962.
JD072331 - Sequence 53355 from Patent EP1572962.
JD296881 - Sequence 277905 from Patent EP1572962.
JD311393 - Sequence 292417 from Patent EP1572962.
JD311395 - Sequence 292419 from Patent EP1572962.
JD311394 - Sequence 292418 from Patent EP1572962.
JD527363 - Sequence 508387 from Patent EP1572962.
DQ598355 - Homo sapiens piRNA piR-36421, complete sequence.
JD031260 - Sequence 12284 from Patent EP1572962.
JD085749 - Sequence 66773 from Patent EP1572962.
JD306515 - Sequence 287539 from Patent EP1572962.
JD067605 - Sequence 48629 from Patent EP1572962.
JD067606 - Sequence 48630 from Patent EP1572962.
DQ589339 - Homo sapiens piRNA piR-56451, complete sequence.
DQ577359 - Homo sapiens piRNA piR-45471, complete sequence.
JD211431 - Sequence 192455 from Patent EP1572962.
DQ577392 - Homo sapiens piRNA piR-45504, complete sequence.
JD471987 - Sequence 453011 from Patent EP1572962.
DQ580663 - Homo sapiens piRNA piR-48775, complete sequence.
DQ580661 - Homo sapiens piRNA piR-48773, complete sequence.
DQ580662 - Homo sapiens piRNA piR-48774, complete sequence.
DQ598327 - Homo sapiens piRNA piR-36393, complete sequence.
JD488689 - Sequence 469713 from Patent EP1572962.
JD302268 - Sequence 283292 from Patent EP1572962.
AK125394 - Homo sapiens cDNA FLJ43404 fis, clone OCBBF2017516.
AK124664 - Homo sapiens cDNA FLJ42673 fis, clone BRAMY2028856.
AL365413 - Homo sapiens EST from clone 223524, 5' end.
JD501855 - Sequence 482879 from Patent EP1572962.
JD140645 - Sequence 121669 from Patent EP1572962.
JD153320 - Sequence 134344 from Patent EP1572962.
JD198489 - Sequence 179513 from Patent EP1572962.
JD527720 - Sequence 508744 from Patent EP1572962.
JD161662 - Sequence 142686 from Patent EP1572962.
JD161663 - Sequence 142687 from Patent EP1572962.
JD547681 - Sequence 528705 from Patent EP1572962.
JD547682 - Sequence 528706 from Patent EP1572962.
JD227654 - Sequence 208678 from Patent EP1572962.
JD089321 - Sequence 70345 from Patent EP1572962.
JD488215 - Sequence 469239 from Patent EP1572962.
JD414812 - Sequence 395836 from Patent EP1572962.
JD120561 - Sequence 101585 from Patent EP1572962.
JD489098 - Sequence 470122 from Patent EP1572962.
JD489099 - Sequence 470123 from Patent EP1572962.
JD308102 - Sequence 289126 from Patent EP1572962.
AK091587 - Homo sapiens cDNA FLJ34268 fis, clone FEBRA2002818.
JD543272 - Sequence 524296 from Patent EP1572962.
JD478586 - Sequence 459610 from Patent EP1572962.
JD463831 - Sequence 444855 from Patent EP1572962.
JD148320 - Sequence 129344 from Patent EP1572962.
JD249871 - Sequence 230895 from Patent EP1572962.
JD537334 - Sequence 518358 from Patent EP1572962.
JD238480 - Sequence 219504 from Patent EP1572962.
JD411923 - Sequence 392947 from Patent EP1572962.
JD117521 - Sequence 98545 from Patent EP1572962.
JD185391 - Sequence 166415 from Patent EP1572962.
JD149432 - Sequence 130456 from Patent EP1572962.
JD088422 - Sequence 69446 from Patent EP1572962.
JD446466 - Sequence 427490 from Patent EP1572962.
JD376797 - Sequence 357821 from Patent EP1572962.
MA587040 - JP 2018138019-A/158966: Polycomb-Associated Non-Coding RNAs.
MA587039 - JP 2018138019-A/158965: Polycomb-Associated Non-Coding RNAs.
MA587038 - JP 2018138019-A/158964: Polycomb-Associated Non-Coding RNAs.
MA587037 - JP 2018138019-A/158963: Polycomb-Associated Non-Coding RNAs.
MA441682 - JP 2018138019-A/13608: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_fasPathway - FAS signaling pathway ( CD95 )
h_deathPathway - Induction of apoptosis through DR3 and DR4/5 Death Receptors
h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF
h_il2rbPathway - IL-2 Receptor Beta Chain in T cell Activation

Reactome (by CSHL, EBI, and GO)

Protein O15519 (Reactome details) participates in the following event(s):

R-HSA-3465429 FLIP(S) and procaspase-8 form heterodimer
R-HSA-5218900 CASP8 activity is inhibited
R-HSA-5675482 Regulation of necroptotic cell death
R-HSA-5213460 RIPK1-mediated regulated necrosis
R-HSA-5218859 Regulated Necrosis
R-HSA-5357801 Programmed Cell Death
R-HSA-3371359 FLIP(L) and procaspase-8 form heterodimer in TRAIL signaling
R-HSA-3371360 FLIP(L) and procaspase-8 form heterodimer in TNF signaling
R-HSA-3465459 FLIP(L) and procaspase-8 form heterodimer in FasL/CD95 signaling
R-HSA-5675456 FLIP(L) and procaspase-8 form heterodimer
R-HSA-3371378 Regulation by c-FLIP
R-HSA-5218900 CASP8 activity is inhibited
R-HSA-140534 Ligand-dependent caspase activation
R-HSA-5675482 Regulation of necroptotic cell death
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-5213460 RIPK1-mediated regulated necrosis
R-HSA-109581 Apoptosis
R-HSA-5218859 Regulated Necrosis
R-HSA-5357801 Programmed Cell Death

-  Other Names for This Gene
  Alternate Gene Symbols: B4DJE0, B7Z9F9, CASH, CASP8AP1, CFLAR_HUMAN, CLARP, ENST00000309955.1, ENST00000309955.2, ENST00000309955.3, ENST00000309955.4, ENST00000309955.5, ENST00000309955.6, ENST00000309955.7, MRIT, NR_147251, O14673, O14674, O14675, O15137, O15138, O15356, O15510, O15519, O43618, O43619, O43620, O60458, O60459, Q53TS6, Q54AF1, Q96TE4, Q9UEW1, uc317oqk.1, uc317oqk.2
UCSC ID: ENST00000309955.8_7
RefSeq Accession: NM_003879.7
Protein: O15519 (aka CFLAR_HUMAN or CFLA_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.