FBXL3
protein-codingF-box and leucine rich repeat protein 3, 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 and is localized in the nucleus. [provided by RefSeq, Jul 2008]
- FBXL3A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011651
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0011651
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FBXL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012158.4. 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 | 4 | 1 | 5 | |||
| missense | 1 | 30 | 31 | |||
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 4 | 1 | 31 | 4 | 1 | 41 |
Highest pathogenic variant AF is 0.00003081571
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036290.1 | 4 | MANE Select | |
| Ensembl | ENSP00000347834.5 | 4 | MANE Select | |
| Ensembl | ENSP00000412183.1 | 4 | Standard | |
| Ensembl | ENSP00000555218.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Circadian rhythm - Homo sapiens (human)
- Circadian Clock
- Post-translational protein modification
- Metabolism of proteins
- Chaperonin-mediated protein folding
Biological Process
- protein polyubiquitination
- protein ubiquitination
- SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
- protein destabilization
- regulation of circadian rhythm
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- ubiquitin protein ligase activity
Cellular Component
- ubiquitin ligase complex
- nucleus
- cytosol
- nuclear body
- SCF ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000355619
- Coding exons
- 4
- Length
- 34591
- Individuals with no LoFs
- 125578
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125581
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.83 | 111 | 233 | 0.477 | 0.0000122 | 2808 |
| Missense (PolyPhen) | 35 | 98.417 | 0.35563 | 1251 | ||
| Synonymous | -0.180 | 84 | 81.9 | 1.03 | 0.00000395 | 820 |
| Loss of Function | 3.53 | 1 | 16.5 | 0.0607 | 9.19e-7 | 215 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation (PubMed:17463251, PubMed:23452855, PubMed:27565346). The SCF(FBXL3) complex mainly acts in the nucleus and mediates ubiquitination and subsequent degradation of CRY1 and CRY2 (PubMed:17463251, PubMed:23452855, PubMed:27565346). Activity of the SCF(FBXL3) complex is counteracted by the SCF(FBXL21) complex (PubMed:23452855). {ECO:0000269|PubMed:17463251, ECO:0000269|PubMed:23452855, ECO:0000269|PubMed:27565346}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.871
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |