CFLAR
protein-codingCASP8 and FADD like apoptosis regulator, the group of Death effector domain containing|Death inducing signaling complex |Ripoptosome|Receptor ligands
Gene summary
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]
- CASP8AP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CFLAR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003879.7. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 34 | 3 | 1 | 38 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 36 | 3 | 2 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003870.4 | 9 | MANE Select | |
| Ensembl | ENSP00000312455.2 | 9 | MANE Select | |
| RefSeq | NP_001120655.1 | 9 | Standard | |
| RefSeq | NP_001120656.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- proteolysis
- apoptotic process
- skeletal muscle tissue development
- response to bacterium
- negative regulation of cardiac muscle cell apoptotic process
Molecular Function
- protease binding
- death receptor binding
- protein binding
- enzyme activator activity
- peptidase activator activity
Cellular Component
- cytoplasm
- cytosol
- death-inducing signaling complex
- CD95 death-inducing signaling complex
- membrane raft
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000309955
- Coding exons
- 9
- Length
- 60584
- Individuals with no LoFs
- 125688
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 42
- Defined
- 125730
- p
- 0.000167
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.19 | 154 | 252 | 0.612 | 0.0000126 | 3164 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000037 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00022 | 0.00013 | rare |
| South Asian | 0.0013 | 0.00078 | notable |
| Other | 0.00036 | 0.00033 | rare |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.487
Intolerance Scores
- LoFtool
- 0.166
- RVIS EVS
- 0.17
- RVIS percentile EVS
- 65.76
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- N
- Indispensability score
- 0.280
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |