CFLAR
CASP8 and FADD like apoptosis regulator, the group of Death effector domain containing|Death inducing signaling complex |Ripoptosome|Receptor ligands
Basic information
Region (hg38): 2:201116154-201176687
Previous symbols: [ "CASP8AP1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFLAR gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 10 | 13 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 10 | 2 | 2 |
Variants in CFLAR
This is a list of pathogenic ClinVar variants found in the CFLAR region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 2-201129887-C-G | not specified | Uncertain significance (Jun 06, 2023) | ||
| 2-201129923-A-G | not specified | Uncertain significance (Jan 31, 2023) | ||
| 2-201133056-T-A | not specified | Uncertain significance (Aug 05, 2024) | ||
| 2-201133071-T-G | not specified | Uncertain significance (Jun 18, 2024) | ||
| 2-201133101-T-G | not specified | Uncertain significance (Jan 17, 2023) | ||
| 2-201133107-G-A | not specified | Uncertain significance (Mar 14, 2023) | ||
| 2-201136003-A-C | not specified | Uncertain significance (Jul 02, 2024) | ||
| 2-201140403-C-G | not specified | Uncertain significance (Dec 06, 2022) | ||
| 2-201140405-A-C | not specified | Likely benign (Aug 19, 2023) | ||
| 2-201145378-C-A | Benign (Feb 16, 2018) | |||
| 2-201145426-G-A | not specified | Likely benign (Mar 16, 2024) | ||
| 2-201145430-A-T | not specified | Uncertain significance (Aug 30, 2022) | ||
| 2-201160530-T-C | not specified | Uncertain significance (Jul 30, 2024) | ||
| 2-201160539-G-A | not specified | Uncertain significance (Oct 09, 2024) | ||
| 2-201160582-G-A | not specified | Uncertain significance (Dec 20, 2021) | ||
| 2-201160659-A-G | not specified | Uncertain significance (Mar 11, 2024) | ||
| 2-201160683-G-T | not specified | Uncertain significance (Apr 15, 2024) | ||
| 2-201160737-C-G | not specified | Uncertain significance (Aug 16, 2022) | ||
| 2-201160763-G-A | Benign (Jun 06, 2018) | |||
| 2-201160783-A-G | not specified | Likely benign (Aug 17, 2022) | ||
| 2-201160828-G-C | not specified | Uncertain significance (Dec 26, 2023) | ||
| 2-201163902-T-C | not specified | Uncertain significance (Nov 29, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CFLAR | protein_coding | protein_coding | ENST00000309955 | 9 | 60584 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000330 | 125688 | 0 | 42 | 125730 | 0.000167 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.19 | 154 | 252 | 0.612 | 0.0000126 | 3164 |
| Missense in Polyphen | 19 | 76.154 | 0.2495 | 1035 | ||
| Synonymous | 1.03 | 84 | 96.9 | 0.867 | 0.00000487 | 903 |
| Loss of Function | 4.67 | 1 | 27.4 | 0.0365 | 0.00000195 | 276 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000366 | 0.0000366 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000218 | 0.000132 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00125 | 0.000784 |
| Other | 0.000361 | 0.000326 |
dbNSFP
Source:
- Function
- 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. {ECO:0000269|PubMed:9880531}.;
- Pathway
- Autophagy - animal - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Necroptosis - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Apoptosis Modulation and Signaling;TNF alpha Signaling Pathway;Nanomaterial induced apoptosis;Apoptosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NF-kB survival signaling;Apoptotic Signaling Pathway;Signal Transduction;hiv-1 nef: negative effector of fas and tnf;Regulation of necroptotic cell death;Dimerization of procaspase-8;Regulation by c-FLIP;Ligand-dependent caspase activation;Caspase activation via extrinsic apoptotic signalling pathway;Apoptosis;CASP8 activity is inhibited;Regulated Necrosis;Programmed Cell Death;RIPK1-mediated regulated necrosis;fas signaling pathway (cd95);TRAIL signaling;Death Receptor Signalling;TNFalpha;TNF;HIV-1 Nef: Negative effector of Fas and TNF-alpha;TRAIL signaling pathway;Validated targets of C-MYC transcriptional repression;FAS (CD95) signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.487
Intolerance Scores
- loftool
- 0.166
- rvis_EVS
- 0.17
- rvis_percentile_EVS
- 65.76
Haploinsufficiency Scores
- pHI
- 0.112
- hipred
- Y
- hipred_score
- 0.743
- ghis
- 0.576
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.280
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cflar
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; immune system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype;
Gene ontology
- Biological process
- proteolysis;apoptotic process;skeletal muscle tissue development;response to bacterium;negative regulation of cardiac muscle cell apoptotic process;positive regulation of peptidase activity;positive regulation of neuron projection development;skeletal muscle atrophy;regulation of skeletal muscle satellite cell proliferation;skeletal myofibril assembly;viral process;cellular response to insulin stimulus;response to testosterone;negative regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;skeletal muscle tissue regeneration;positive regulation of NF-kappaB transcription factor activity;regulation of necroptotic process;negative regulation of necroptotic process;positive regulation of ERK1 and ERK2 cascade;cellular response to epidermal growth factor stimulus;cellular response to estradiol stimulus;cellular response to hypoxia;cellular response to dexamethasone stimulus;cellular response to nitric oxide;positive regulation of glomerular mesangial cell proliferation;negative regulation of myoblast fusion;regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;positive regulation of extracellular matrix organization;negative regulation of reactive oxygen species biosynthetic process;negative regulation of cellular response to transforming growth factor beta stimulus;negative regulation of hepatocyte apoptotic process;positive regulation of hepatocyte proliferation;negative regulation of extrinsic apoptotic signaling pathway
- Cellular component
- cytoplasm;cytosol;death-inducing signaling complex;CD95 death-inducing signaling complex;membrane raft;ripoptosome
- Molecular function
- protease binding;death receptor binding;protein binding;enzyme activator activity;peptidase activator activity;protein-containing complex binding;protein heterodimerization activity;cysteine-type endopeptidase activity involved in apoptotic process