FBXL17

Chr 5

F-box and leucine rich repeat protein 17

Also known as: FBXO13, Fbl17, Fbx13

NCBI Gene: 64839 ENSG00000145743 UniProt: Q9UF56

Members of the F-box protein family, such as FBXL17, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

Research

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.15

Clinical Summary— FBXL17

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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.

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ClinVar Variants

113 VUS of 127 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.15LOEUF

pLI 0.999

Z-score 4.15

OE 0.00 (0.00–0.15)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.17Z-score

OE missense 0.59 (0.51–0.68)

133 obs / 224.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.15)

0≤0.351.4

Missense OE?0.59 (0.51–0.68)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 0 / 20.0Missense obs/exp: 133 / 224.4Syn Z: -0.88

This gene — mechanism propensity

0.3494th %ile

GOF

0.5759th %ile

LOF

0.78top 5%

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

LOFprediction above median · LOEUF 0.15

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

127 submitted variants in ClinVar

ClinVar

Classification Summary

VUS113

Likely Benign5

Benign2

113

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	113	0	113
Likely Benign	1	4	5
Benign	1	1	2
Total	115	5	120

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap FBXL17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →