FBXL2

F-box and leucine rich repeat protein 2, the group of F-box and leucine rich repeat proteins

Basic information

Region (hg38): 3:33277024-33403662

Links

ENSG00000153558 ∙ NCBI:25827 ∙ OMIM:605652 ∙ HGNC:13598 ∙ Uniprot:Q9UKC9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBXL2 gene.

• Inborn genetic diseases (6 variants)

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						0
missense			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	0	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)
3-33373142-G-A		not specified	Uncertain significance (Apr 29, 2022)
3-33373305-G-C		not specified	Likely benign (Oct 02, 2023)
3-33377290-G-A		not specified	Uncertain significance (Aug 30, 2022)
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)
3-33396189-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 03, 2022)
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)
3-33402834-G-A		not specified	Uncertain significance (Jan 29, 2024)
3-33402835-A-G		not specified	Uncertain significance (Jan 29, 2024)
3-33402853-G-T		not specified	Likely benign (Nov 10, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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