FBXO39

Chr 17

F-box protein 39

Also known as: CT144, FBOX39, Fbx39

NCBI Gene: 162517ENSG00000177294UniProt: Q8N4B4OMIM: 609106

FBXO39 encodes a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes, which target specific proteins for degradation through ubiquitination. The gene shows minimal constraint against loss-of-function variants in the general population, with very low probability of being loss-of-function intolerant. Currently, no established Mendelian diseases have been definitively linked to FBXO39 mutations in the medical literature.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.99
Clinical Summary— FBXO39
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 72 VUS of 101 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.58
OE 0.57 (0.34–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.06Z-score
OE missense 1.01 (0.91–1.12)
250 obs / 247.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.34–0.99)
0≤0.351.4
Missense OE1.01 (0.91–1.12)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 9 / 15.8Missense obs/exp: 250 / 247.5Syn Z: 1.28
DN
0.6260th %ile
GOF
0.5661th %ile
LOF
0.2386th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS72
Likely Benign4
Benign2
19
Pathogenic
1
Likely Pathogenic
72
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
64
8
0
72
Likely Benign
0
4
0
0
4
Benign
0
1
1
0
2
Total06929098

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

View in ClinVar →

Protein Context — Lollipop Plot

FBXO39 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients