FBXL12
protein-codingF-box and leucine rich repeat protein 12, the group of F-box and leucine rich repeat proteins
Gene summary
Members of the F-box protein family, such as FBXL12, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), 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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.5 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 FBXL12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017703.3. 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 | 1 | 1 | ||||
| missense | 57 | 1 | 58 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 59 | 1 | 0 | 60 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060173.1 | 3 | MANE Select | |
| Ensembl | ENSP00000247977.3 | 3 | MANE Select | |
| RefSeq | NP_001303865.1 | 2 | Standard | |
| RefSeq | NP_001303866.1 | 1 | 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
- G2/M transition of mitotic cell cycle
- protein polyubiquitination
- SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
- post-translational protein modification
- regulation of cell cycle
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- ubiquitin protein ligase activity
Cellular Component
- nucleus
- cytosol
- SCF ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000247977
- Coding exons
- 3
- Length
- 17550
- Individuals with no LoFs
- 125692
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125701
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.919 | 169 | 206 | 0.820 | 0.0000125 | 2055 |
| Missense (PolyPhen) | 33 | 44.937 | 0.73437 | 492 | ||
| Synonymous | 1.24 | 75 | 89.9 | 0.834 | 0.00000507 | 725 |
| Loss of Function | 1.96 | 4 | 11.0 | 0.363 | 7.01e-7 | 94 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000050 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00021 | 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. Mediates the polyubiquitination and proteasomal degradation of CAMK1 leading to disruption of cyclin D1/CDK4 complex assembly which results in G1 cell cycle arrest in lung epithelia. {ECO:0000269|PubMed:23707388}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.646
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.844
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |