FBXL16

Chr 16

F-box and leucine rich repeat protein 16

Also known as: C16orf22, Fbl16, c380A1.1

NCBI Gene: 146330ENSG00000127585UniProt: Q8N461

FBXL16 encodes a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes that target specific proteins for ubiquitination and degradation. Loss-of-function mutations cause autosomal dominant neurodevelopmental disorders through haploinsufficiency, as evidenced by the high pLI score of 0.97 and low LOEUF score of 0.31 indicating strong intolerance to protein-truncating variants.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
5
Pubs (1 yr)
49
P/LP submissions
0%
P/LP missense
0.31
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— FBXL16
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
48 unique Pathogenic / Likely Pathogenic· 56 VUS of 124 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.31LOEUF
pLI 0.970
Z-score 3.38
OE 0.07 (0.02–0.31)
Highly constrained

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

Missense Constraint
3.14Z-score
OE missense 0.47 (0.40–0.54)
128 obs / 274.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.07 (0.02–0.31)
0≤0.351.4
Missense OE0.47 (0.40–0.54)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 1 / 15.2Missense obs/exp: 128 / 274.5Syn Z: -0.37
DN
0.3792th %ile
GOF
0.5169th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.31

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

124 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
VUS56
Likely Benign4
Benign7
48
Pathogenic
56
VUS
4
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
48
0
48
Likely Pathogenic
0
0
0
0
0
VUS
0
41
15
0
56
Likely Benign
0
1
1
2
4
Benign
0
0
7
0
7
Total042712115

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

View in ClinVar →

Protein Context — Lollipop Plot

FBXL16 · 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
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 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