FBXO10

protein-coding

F-box protein 10, the group of F-boxes other

Gene summary

Members of the F-box protein family, such as FBXO10, 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

NM_012166.3

Inheritance

—

ClinVar variants

U:109B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr9:37,510,892-37,576,380

External References & Databases

Ensembl (ENSG00000147912)

Transcript & Mutation Effects

hg38 • Region Span ~65.5 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 FBXO10 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 101

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012166.3. 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 clinvar	2 clinvar	4 clinvar	7
missense			101 clinvar	3 clinvar	1 clinvar	105
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	109	5	5	119

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012166.3	RefSeq	NP_036298.2	10	MANE Select
ENST00000432825.7	Ensembl	ENSP00000403802.2	10	MANE Select
ENST00000276960.7	Ensembl	ENSP00000276960.7	5	Standard
ENST00000541607.1	Ensembl	ENSP00000440061.1	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

protein polyubiquitination
ubiquitin-dependent protein catabolic process
apoptotic process
protein ubiquitination
regulation of apoptotic process

Molecular Function

ubiquitin-protein transferase activity
protein binding

Cellular Component

ubiquitin ligase complex
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000432825
Coding exons: 10
Length: 77983
Individuals with no LoFs: 124573
Homozygous LoFs: 0
Heterozygous LoFs: 110
Defined: 124683
p: 0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.89	466	596	0.782	0.0000370	6263
Missense (PolyPhen)		115	189.97	0.60535		1966
Synonymous	1.85	200	236	0.847	0.0000146	1924
Loss of Function	3.25	16	37.5	0.427	0.00000210	403

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00026	rare
Latino/Admixed American	0.00030	0.00029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000056	0.000056	rare
Finnish	0.0024	0.0024	notable
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00041	0.00033	rare
Other	0.00084	0.00083	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F- box protein)-type E3 ubiquitin ligase complex. The SCF(FBXO10) complex mediates ubiquitination and degradation of BCL2, an antiapoptotic protein, thereby playing a role in apoptosis by controlling the stability of BCL2. {ECO:0000269|PubMed:23431138}.;
Disease: DISEASE: Note=Defects in FBXO10 may be a cause of diffuse large B- cell lymphoma by allowing the accumulation of BCL2, an oncoprotein that has a critical role in lymphomas. {ECO:0000269|PubMed:23431138}.;

Intolerance Scores

LoFtool: 0.719
RVIS EVS: -1.99
RVIS percentile EVS: 1.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.296

Gene Damage Prediction

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