FBXL6
Chr 8F-box and leucine rich repeat protein 6
Also known as: FBL6, FBL6A, PP14630
The protein serves as a substrate-recognition component of the SCF E3 ubiquitin ligase complex, which targets specific proteins for degradation through the ubiquitin-proteasome pathway. Mutations cause autosomal recessive developmental delay with intellectual disability, seizures, and movement disorders. The gene shows moderate constraint against loss-of-function variants, suggesting some tolerance to haploinsufficiency.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
217 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 51 | 0 | 51 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 107 | 13 | 0 | 120 |
Likely Benign | 0 | 7 | 1 | 3 | 11 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 114 | 71 | 3 | 188 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FBXL6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools