FBXL14

Chr 12

F-box and leucine rich repeat protein 14

Also known as: Fbl14

FBXL14 encodes a substrate-recognition component of SCF ubiquitin ligase complexes that targets specific proteins like SNAI1 for degradation through the ubiquitin-proteasome pathway. Mutations cause autosomal recessive intellectual disability with dysmorphic features and behavioral abnormalities. This gene is highly constrained against loss-of-function mutations, suggesting critical developmental importance.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
65
P/LP submissions
0%
P/LP missense
0.47
LOEUF
Mechanism
Clinical SummaryFBXL14
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
65 unique Pathogenic / Likely Pathogenic· 41 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.825
Z-score 2.66
OE 0.10 (0.030.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.95Z-score
OE missense 0.48 (0.410.55)
119 obs / 250.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.030.47)
00.351.4
Missense OE0.48 (0.410.55)
00.61.4
Synonymous OE1.36
01.21.6
LoF obs/exp: 1 / 10.1Missense obs/exp: 119 / 250.1Syn Z: -3.00

ClinVar Variant Classifications

115 submitted variants in ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic3
VUS41
Likely Benign4
Benign1
62
Pathogenic
3
Likely Pathogenic
41
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
3
0
3
VUS
0
33
8
0
41
Likely Benign
0
0
2
2
4
Benign
0
0
0
1
1
Total033753111

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

View in ClinVar →

Protein Context — Lollipop Plot

FBXL14 · 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.

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Clinical Literature
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