FBXO4
protein-codingF-box protein 4, the group of F-boxes other
Gene summary
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 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 Fbxs class. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.5 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 FBXO4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012176.3. 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 | 2 | 2 | 4 | |||
| missense | 53 | 3 | 56 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 56 | 5 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036308.1 | 7 | MANE Select | |
| Ensembl | ENSP00000281623.3 | 7 | MANE Select | |
| RefSeq | NP_001284366.1 | 6 | Standard | |
| RefSeq | NP_277019.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Post-translational protein modification
- Metabolism of proteins
- Chaperonin-mediated protein folding
- Immune System
Biological Process
- protein polyubiquitination
- aging
- posttranscriptional regulation of gene expression
- protein ubiquitination
- cellular homeostasis
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- protein homodimerization activity
- ubiquitin protein ligase activity
Cellular Component
- ubiquitin ligase complex
- cytoplasm
- cytosol
- SCF ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000281623
- Coding exons
- 7
- Length
- 16490
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125743
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.649 | 156 | 181 | 0.864 | 0.00000847 | 2524 |
| Missense (PolyPhen) | 60 | 69.502 | 0.86328 | 930 | ||
| Synonymous | -0.316 | 63 | 59.9 | 1.05 | 0.00000262 | 723 |
| Loss of Function | 1.40 | 11 | 17.3 | 0.636 | 8.93e-7 | 231 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00014 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00010 | 0.000092 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00040 | 0.00039 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes ubiquitination of CCND1 and its subsequent proteasomal degradation. Recognizes TERF1 and promotes its ubiquitination together with UBE2D1. {ECO:0000269|PubMed:10531035, ECO:0000269|PubMed:16275645, ECO:0000269|PubMed:18598945, ECO:0000269|PubMed:20159592, ECO:0000269|PubMed:20181953}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.792
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.22
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.957
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |