FBXW12
protein-codingF-box and WD repeat domain containing 12, the group of F-box and WD repeat domain containing|WD repeat domain containing
Gene summary
Members of the F-box protein family, such as FBXW12, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603034), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]
- FBXO35
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.0 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 FBXW12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_207102.2. 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 | ||||
| missense | 60 | 9 | 69 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 60 | 11 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_996985.2 | 10 | MANE Select | |
| Ensembl | ENSP00000296438.5 | 10 | MANE Select | |
| RefSeq | NP_001153399.1 | 9 | Standard | |
| RefSeq | NP_001153401.1 | 10 | Standard |
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
- post-translational protein modification
Molecular Function
- ubiquitin-protein transferase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296438
- Coding exons
- 10
- Length
- 28958
- Individuals with no LoFs
- 125641
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 103
- Defined
- 125744
- p
- 0.000410
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.402 | 234 | 252 | 0.929 | 0.0000126 | 3063 |
| Missense (PolyPhen) | 51 | 60.934 | 0.83697 | 778 | ||
| Synonymous | 1.33 | 80 | 96.6 | 0.828 | 0.00000521 | 870 |
| Loss of Function | 1.40 | 18 | 25.6 | 0.702 | 0.00000136 | 278 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0031 | 0.0031 | notable |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.00098 | 0.00098 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F- box protein)-type E3 ubiquitin ligase complex. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0621
Intolerance Scores
- LoFtool
- 0.992
- RVIS EVS
- 0.78
- RVIS percentile EVS
- 87.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0467
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |