FBH1
protein-codingF-box DNA helicase 1, the group of F-boxes other|DNA helicases
Gene summary
This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbx class. It contains an F-box motif and seven conserved helicase motifs, and has both DNA-dependent ATPase and DNA unwinding activities. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
- FBXO18
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.4 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 FBH1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_178150.3. 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 | 3 | ||||
| missense | 138 | 8 | 146 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 148 | 8 | 0 | 156 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_835363.1 | 21 | MANE Select | |
| Ensembl | ENSP00000355415.4 | 21 | MANE Select | |
| RefSeq | NP_001245381.1 | 20 | Standard | |
| RefSeq | NP_001245382.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- double-strand break repair via homologous recombination
- recombinational repair
- DNA catabolic process, endonucleolytic
- positive regulation of protein phosphorylation
- DNA repair
Molecular Function
- DNA helicase activity
- double-stranded DNA binding
- single-stranded DNA binding
- protein binding
- DNA translocase activity
Cellular Component
- chromatin
- nucleus
- SCF ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379999
- Coding exons
- 22
- Length
- 48022
- Individuals with no LoFs
- 125695
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 53
- Defined
- 125748
- p
- 0.000211
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.82 | 453 | 656 | 0.690 | 0.0000388 | 7211 |
| Missense (PolyPhen) | 92 | 216.22 | 0.4255 | 2474 | ||
| Synonymous | 0.493 | 250 | 260 | 0.961 | 0.0000170 | 2085 |
| Loss of Function | 4.69 | 18 | 55.8 | 0.323 | 0.00000289 | 636 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.0016 | 0.0016 | notable |
| East Asian | 0.00082 | 0.00082 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 3'-5' DNA helicase and substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex that plays a key role in response to stalled/damaged replication forks (PubMed:11956208, PubMed:23393192). Involved in genome maintenance by acting as an anti-recombinogenic helicase and preventing extensive strand exchange during homologous recombination: promotes RAD51 filament dissolution from stalled forks, thereby inhibiting homologous recombination and preventing excessive recombination (PubMed:17724085, PubMed:19736316). Also promotes cell death and DNA double-strand breakage in response to replication stress: together with MUS81, promotes the endonucleolytic DNA cleavage following prolonged replication stress via its helicase activity, possibly to eliminate cells with excessive replication stress (PubMed:23319600, PubMed:23361013). Plays a major role in remodeling of stalled DNA forks by catalyzing fork regression, in which the fork reverses and the two nascent DNA strands anneal (PubMed:25772361). In addition to the helicase activity, also acts as the substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex, a complex that mediates ubiquitination of RAD51, leading to regulate RAD51 subcellular location (PubMed:25585578). {ECO:0000269|PubMed:11956208, ECO:0000269|PubMed:17724085, ECO:0000269|PubMed:19736316, ECO:0000269|PubMed:23319600, ECO:0000269|PubMed:23361013, ECO:0000269|PubMed:25585578, ECO:0000269|PubMed:25772361}.;
- Disease
- DISEASE: Note=Defects in FBH1 are frequently observed in melanomas, resulting in increased survival in response to replicative stress. Its inactivation may play a role in oncogenic transformation. {ECO:0000269|PubMed:23466708}.;
Recessive Scores
- pRec
- 0.0981
Intolerance Scores
- RVIS EVS
- -2.03
- RVIS percentile EVS
- 1.68
Essentials
- Essential (gene trap)
- N