FBXL5
protein-codingF-box and leucine rich repeat protein 5, the group of F-box and leucine rich repeat proteins
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 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 Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~77.3 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 FBXL5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012161.4. 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 | ||||
| missense | 77 | 77 | ||||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 83 | 0 | 0 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036293.1 | 11 | MANE Select | |
| Ensembl | ENSP00000344866.3 | 11 | MANE Select | |
| RefSeq | NP_001180463.1 | 11 | Standard | |
| RefSeq | NP_001180464.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Chaperonin-mediated protein folding
- Immune System
- Association of TriC/CCT with target proteins during biosynthesis
Biological Process
- protein polyubiquitination
- ubiquitin-dependent protein catabolic process
- cellular iron ion homeostasis
- protein ubiquitination
- SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Molecular Function
- ubiquitin-protein transferase activity
- iron ion binding
- protein binding
Cellular Component
- ubiquitin ligase complex
- cytosol
- SCF ubiquitin ligase complex
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000341285
- Coding exons
- 11
- Length
- 77141
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125728
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.85 | 256 | 354 | 0.724 | 0.0000174 | 4567 |
| Missense (PolyPhen) | 67 | 140.41 | 0.47719 | 1849 | ||
| Synonymous | -0.165 | 127 | 125 | 1.02 | 0.00000644 | 1261 |
| Loss of Function | 4.77 | 3 | 32.2 | 0.0931 | 0.00000151 | 428 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00052 | 0.00049 | rare |
| Latino/Admixed American | 0.000031 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2. Upon high iron and oxygen level, it specifically recognizes and binds IREB2/IRP2, promoting its ubiquitination and degradation by the proteasome. Promotes ubiquitination and subsequent degradation of DCTN1/p150-glued. {ECO:0000269|PubMed:17532294, ECO:0000269|PubMed:19762596, ECO:0000269|PubMed:19762597}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.311
- RVIS EVS
- -0.96
- RVIS percentile EVS
- 9.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.773
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |