FBXL2
Basic information
Region (hg38): 3:33277025-33403662
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBXL2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 1 | |||||
missense | 7 | |||||
nonsense | 0 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 0 | |||||
non coding | 0 | |||||
Total | 0 | 0 | 7 | 1 | 0 |
Variants in FBXL2
This is a list of pathogenic ClinVar variants found in the FBXL2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
3-33359323-G-T | not specified | Uncertain significance (Apr 27, 2023) | ||
3-33364629-G-A | not specified | Uncertain significance (Apr 19, 2023) | ||
3-33364658-G-A | not specified | Uncertain significance (Aug 14, 2024) | ||
3-33373118-T-C | not specified | Uncertain significance (Dec 07, 2024) | ||
3-33373142-G-A | not specified | Uncertain significance (Apr 29, 2022) | ||
3-33373305-G-C | not specified | Likely benign (Oct 02, 2023) | ||
3-33375289-G-A | not specified | Uncertain significance (Aug 25, 2024) | ||
3-33375379-C-T | not specified | Uncertain significance (Jul 26, 2024) | ||
3-33375384-C-A | not specified | Uncertain significance (Oct 25, 2024) | ||
3-33377290-G-A | not specified | Uncertain significance (Nov 10, 2024) | ||
3-33377320-C-A | not specified | Uncertain significance (Jun 28, 2024) | ||
3-33377332-G-A | not specified | Uncertain significance (Nov 11, 2024) | ||
3-33378697-A-C | not specified | Uncertain significance (Jul 13, 2022) | ||
3-33384057-T-G | not specified | Uncertain significance (Apr 07, 2022) | ||
3-33385543-G-A | not specified | Uncertain significance (Mar 12, 2024) | ||
3-33393346-C-A | not specified | Uncertain significance (Dec 16, 2022) | ||
3-33393377-G-T | not specified | Uncertain significance (May 24, 2024) | ||
3-33396189-T-C | not specified | Likely benign (Jul 14, 2021) | ||
3-33396229-G-C | not specified | Uncertain significance (Sep 17, 2021) | ||
3-33396246-G-A | not specified | Uncertain significance (Oct 29, 2024) | ||
3-33396278-G-A | not specified | Uncertain significance (Sep 26, 2024) | ||
3-33400264-T-C | not specified | Uncertain significance (May 23, 2023) | ||
3-33400967-C-T | not specified | Likely benign (May 08, 2023) | ||
3-33400996-T-C | not specified | Uncertain significance (Dec 09, 2023) | ||
3-33402820-T-G | not specified | Uncertain significance (Oct 29, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
FBXL2 | protein_coding | protein_coding | ENST00000484457 | 15 | 126638 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.00753 | 0.992 | 125723 | 0 | 25 | 125748 | 0.0000994 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 2.46 | 132 | 239 | 0.552 | 0.0000137 | 2746 |
Missense in Polyphen | 29 | 78.268 | 0.37052 | 908 | ||
Synonymous | 0.820 | 85 | 95.2 | 0.893 | 0.00000551 | 827 |
Loss of Function | 3.67 | 10 | 32.6 | 0.307 | 0.00000217 | 315 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000218 | 0.000213 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.000163 | 0.000163 |
Finnish | 0.0000462 | 0.0000462 |
European (Non-Finnish) | 0.0000968 | 0.0000967 |
Middle Eastern | 0.000163 | 0.000163 |
South Asian | 0.000196 | 0.000196 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin. This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin. Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (PubMed:22020328, PubMed:22323446). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (PubMed:23604317). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (By similarity). {ECO:0000250|UniProtKB:Q8BH16, ECO:0000269|PubMed:22020328, ECO:0000269|PubMed:22323446, ECO:0000269|PubMed:23604317}.;
Intolerance Scores
- loftool
- 0.725
- rvis_EVS
- -0.21
- rvis_percentile_EVS
- 38.58
Haploinsufficiency Scores
- pHI
- 0.599
- hipred
- Y
- hipred_score
- 0.746
- ghis
- 0.579
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.178
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fbxl2
- Phenotype
Gene ontology
- Biological process
- cellular protein modification process;proteolysis;ubiquitin-dependent protein catabolic process;protein monoubiquitination;regulation of autophagy;regulation of phosphatidylinositol 3-kinase signaling;viral process;protein ubiquitination;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;modulation by host of viral RNA genome replication
- Cellular component
- cytoplasm;membrane;SCF ubiquitin ligase complex
- Molecular function
- ubiquitin-protein transferase activity;protein binding;calmodulin binding;protein phosphatase binding;phosphatidylinositol 3-kinase regulatory subunit binding