FBXL22
protein-codingF-box and leucine rich repeat protein 22, the group of F-box and leucine rich repeat proteins
Gene summary
This gene encodes a member of the F-box protein family. This F-box protein interacts with S-phase kinase-associated protein 1A and cullin in order to form SCF complexes which function as ubiquitin ligases.[provided by RefSeq, Sep 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.1 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 FBXL22 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001367807.1. 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 | 0 | |||||
| missense | 20 | 1 | 21 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 20 | 1 | 0 | 21 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001354736.1 | 2 | MANE Select | |
| Ensembl | ENSP00000492359.1 | 2 | MANE Select | |
| RefSeq | NP_001354737.1 | 2 | Standard | |
| RefSeq | NP_001354738.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| fbxl22 | Danio rerio | Structure: heart Quality: decreased contractility abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Immune System
- Adaptive Immune System
- Antigen processing: Ubiquitination & Proteasome degradation
Biological Process
- protein polyubiquitination
- proteasome-mediated ubiquitin-dependent protein catabolic process
- post-translational protein modification
Molecular Function
- ubiquitin-protein transferase activity
- ubiquitin protein ligase activity
Cellular Component
- nucleolus
- cytosol
- Z disc
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360587
- Coding exons
- 2
- Length
- 5076
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125732
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.589 | 164 | 144 | 1.14 | 0.00000797 | 1554 |
| Missense (PolyPhen) | 69 | 60.546 | 1.1396 | 651 | ||
| Synonymous | -0.685 | 69 | 62.1 | 1.11 | 0.00000343 | 536 |
| Loss of Function | -0.0711 | 4 | 3.85 | 1.04 | 1.66e-7 | 38 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00073 | 0.00069 | rare |
| European (Non-Finnish) | 0.000057 | 0.000053 | rare |
| South Asian | 0.000035 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F- box protein)-type E3 ubiquitin ligase complex. Promotes ubiquitination of sarcomeric proteins alpha-actinin-2 (ACTN2) and filamin-C (FLNC). {ECO:0000269|PubMed:22972877}.;
Recessive Scores
- pRec
- 0.0858
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.178
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |