FBXO3

protein-coding

F-box protein 3, the group of F-boxes other

Gene summary

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. Alternative splicing of this gene generates 2 transcript variants diverging at the 3' end. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012175.4

Inheritance

—

ClinVar variants

U:44B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr11:33,740,939-33,774,543

External References & Databases

Ensembl (ENSG00000110429)

Transcript & Mutation Effects

hg38 • Region Span ~33.6 kb

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GenCC 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 FBXO3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 39

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012175.4. 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 clinvar	2 clinvar		3
missense			40 clinvar			40
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	44	2	0	46

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012175.4	RefSeq	NP_036307.2	11	MANE Select
ENST00000265651.8	Ensembl	ENSP00000265651.3	11	MANE Select
NM_033406.4	RefSeq	NP_208385.1	10	Standard
ENST00000448981.6	Ensembl	ENSP00000408836.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
protein ubiquitination

Molecular Function

ubiquitin-protein transferase activity
protein binding

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265651
Coding exons: 11
Length: 33605
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125746
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.15	168	267	0.630	0.0000143	3074
Missense (PolyPhen)		41	92.671	0.44242		1121
Synonymous	1.00	80	92.3	0.867	0.00000497	864
Loss of Function	4.52	4	31.3	0.128	0.00000201	336

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000061	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate recognition component of the SCF (SKP1-CUL1-F- box protein)-type E3 ubiquitin ligase complex. Mediates the ubiquitination of HIPK2 and probably that of EP300, leading to rapid degradation by the proteasome. In the presence of PML, HIPK2 ubiquitination still occurs, but degradation is prevented. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53- dependent transactivation. {ECO:0000269|PubMed:18809579}.;

Recessive Scores

pRec: 0.191

Intolerance Scores

LoFtool: 0.430
RVIS EVS: -0.36
RVIS percentile EVS: 28.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.984

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium