FBXO8

protein-coding

F-box protein 8, the group of F-boxes other|Sec7 family

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. It contains a C-terminal amino acid sequence that bears a significant similarity with a portion of yeast Sec7p, a critical regulator of vesicular protein transport. This human protein may interact with ADP-ribosylation factor(s)(ARFs) and exhibit ARF-GEF (guanine nucleotide exchange factor) activity. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012180.3

Inheritance

—

ClinVar variants

U:20B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr4:174,236,658-174,283,667

External References & Databases

Ensembl (ENSG00000164117)

Transcript & Mutation Effects

hg38 • Region Span ~47.0 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 FBXO8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 17

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012180.3. 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		1 clinvar	2
missense			17 clinvar		1 clinvar	18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	20	0	2	22

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012180.3	RefSeq	NP_036312.2	5	MANE Select
ENST00000393674.7	Ensembl	ENSP00000377280.2	5	MANE Select
ENST00000503293.5	Ensembl	ENSP00000422905.1	6	Standard
ENST00000503293.6	Ensembl	ENSP00000422905.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arf6 signaling events

Biological Process

ubiquitin-dependent protein catabolic process
regulation of ARF protein signal transduction

Molecular Function

ARF guanyl-nucleotide exchange factor activity

Cellular Component

ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393674
Coding exons: 5
Length: 47607
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125742
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.94	99	170	0.582	0.00000860	2122
Missense (PolyPhen)		17	57.384	0.29625		753
Synonymous	0.244	56	58.4	0.959	0.00000282	573
Loss of Function	2.82	3	14.6	0.205	7.60e-7	179

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May promote guanine-nucleotide exchange on an ARF. Promotes the activation of ARF through replacement of GDP with GTP (Potential). {ECO:0000305}.;

Recessive Scores

pRec: 0.144

Intolerance Scores

LoFtool: 0.236
RVIS EVS: -0.18
RVIS percentile EVS: 39.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.820

Gene Damage Prediction

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