FBXO38

Chr 5AD

F-box protein 38

Also known as: Fbx38, HMN2D, HMND6, MOKA, SP329

NCBI Gene: 81545ENSG00000145868UniProt: Q6PIJ6

This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

Primary Disease Associations & Inheritance

Neuronopathy, distal hereditary motor, autosomal dominant 6MIM #615575
AD
0
Active trials
1
Pathogenic / LP
480
ClinVar variants
4
Pubs (1 yr)
2.8
Missense Z
0.27
LOEUF· LoF intolerant
Clinical Summary— FBXO38
🧬
Gene-Disease Validity (ClinGen)
distal hereditary motor neuropathy · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
1 Pathogenic / Likely Pathogenic· 266 VUS of 480 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.999
Z-score 6.05
OE 0.15 (0.09–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.81Z-score
OE missense 0.68 (0.63–0.74)
425 obs / 622.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.09–0.27)
0≤0.351.4
Missense OE0.68 (0.63–0.74)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 9 / 59.2Missense obs/exp: 425 / 622.5Syn Z: 0.56
LOF
DN
0.3097th %ile
GOF
0.3392th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

480 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS266
Likely Benign170
Benign38
Conflicting5
1
Pathogenic
266
VUS
170
Likely Benign
38
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
0
0
0
0
0
VUS
4
243
16
3
266
Likely Benign
0
4
80
86
170
Benign
0
2
33
3
38
Conflicting
—5
Total425012992480

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

View in ClinVar →

FBXO38 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 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