FAF1
protein-codingFas associated factor 1, the group of UBX domain containing
Gene summary
Interaction of Fas ligand (TNFSF6) with the FAS antigen (TNFRSF6) mediates programmed cell death, also called apoptosis, in a number of organ systems. The protein encoded by this gene binds to FAS antigen and can initiate apoptosis or enhance apoptosis initiated through FAS antigen. Initiation of apoptosis by the protein encoded by this gene requires a ubiquitin-like domain but not the FAS-binding domain. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~523.2 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 FAF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007051.3. 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 | 3 | 2 | 5 | |||
| missense | 65 | 65 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 77 | 2 | 0 | 79 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008982.1 | 19 | MANE Select | |
| Ensembl | ENSP00000379457.2 | 19 | MANE Select | |
| Ensembl | ENSP00000434929.1 | 13 | Standard | |
| Ensembl | ENSP00000559013.1 | 19 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| faf1 | Danio rerio | Structure: ceratobranchial cartilage Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Necroptosis - Homo sapiens (human)
- Retinoblastoma (RB) in Cancer
- Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation
- VEGFA-VEGFR2 Signaling Pathway
- fas signaling pathway (cd95)
Biological Process
- apoptotic process
- cytoplasmic sequestering of NF-kappaB
- cell death
- positive regulation of cell death
- regulation of cell adhesion
Molecular Function
- protein binding
- protein kinase regulator activity
- protein kinase binding
- protein domain specific binding
- heat shock protein binding
Cellular Component
- nucleus
- nuclear envelope
- cytosol
- CD95 death-inducing signaling complex
- VCP-NPL4-UFD1 AAA ATPase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396153
- Coding exons
- 19
- Length
- 520786
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125747
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.13 | 246 | 359 | 0.684 | 0.0000195 | 4273 |
| Missense (PolyPhen) | 45 | 95.515 | 0.47113 | 1074 | ||
| Synonymous | 1.27 | 107 | 125 | 0.855 | 0.00000669 | 1202 |
| Loss of Function | 5.29 | 5 | 41.9 | 0.119 | 0.00000227 | 480 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00020 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ubiquitin-binding protein (PubMed:19722279). Required for the progression of DNA replication forks by targeting DNA replication licensing factor CDT1 for degradation (PubMed:26842564). Potentiates but cannot initiate FAS-induced apoptosis (By similarity). {ECO:0000250|UniProtKB:P54731, ECO:0000269|PubMed:19722279, ECO:0000269|PubMed:26842564}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.189
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |