FBXO8

Chr 4

F-box protein 8

Also known as: DC10, FBS, FBX8

The protein functions as both a component of SCF ubiquitin ligase complexes that target proteins for degradation and as a guanine nucleotide exchange factor that activates ADP-ribosylation factors involved in vesicular transport. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and progressive brain atrophy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.53), consistent with its role in fundamental cellular processes.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
68
P/LP submissions
0%
P/LP missense
0.53
LOEUF
Mechanism
Clinical SummaryFBXO8
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📋
ClinVar Variants
68 unique Pathogenic / Likely Pathogenic· 24 VUS of 109 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.486
Z-score 2.82
OE 0.21 (0.090.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.94Z-score
OE missense 0.58 (0.490.69)
99 obs / 170.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.090.53)
00.351.4
Missense OE0.58 (0.490.69)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 3 / 14.6Missense obs/exp: 99 / 170.1Syn Z: 0.24

ClinVar Variant Classifications

109 submitted variants in ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic2
VUS24
Benign3
66
Pathogenic
2
Likely Pathogenic
24
VUS
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
66
0
66
Likely Pathogenic
0
0
2
0
2
VUS
0
17
7
0
24
Likely Benign
0
0
0
0
0
Benign
0
1
1
1
3
Total01876195

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FBXO8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗