FBXL18

Chr 7

F-box and leucine rich repeat protein 18

Also known as: Fbl18

NCBI Gene: 80028 ENSG00000155034 UniProt: Q96ME1 OMIM: 609084

FBXL18 encodes a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes that targets proteins like FBXL7 for polyubiquitylation and proteasomal degradation. The gene shows very low constraint to loss-of-function variants (pLI <0.01, LOEUF 0.88), but no established human disease associations have been reported to date. Clinical significance of FBXL18 variants remains uncertain pending additional evidence.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of a family of proteins that contain an approximately 40-amino acid F-box motif. This motif is important for interaction with SKP1 and for targeting some proteins for degradation. The encoded protein has been shown to control the cellular level of FBXL7, a protein that induces mitotic arrest, by targeting it for polyubiquitylation and proteasomal degradation. Members of the F-box protein family, such as FBXL18, are characterized by an approximately 40-amino acid F-box motif. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains. [provided by RefSeq, Mar 2016]

OMIM ResearchGenerating clinical summary…

LOEUF 0.88

Clinical Summary— FBXL18

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

69 VUS of 88 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 1.94

OE 0.50 (0.30–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.80Z-score

OE missense 0.77 (0.71–0.84)

369 obs / 479.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.30–0.88)

0≤0.351.4

Missense OE?0.77 (0.71–0.84)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 9 / 17.9Missense obs/exp: 369 / 479.7Syn Z: -0.14

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

VUS69

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	68	0	69
Likely Benign	0	2	3	5
Benign	0	0	0	0
Total	1	70	3	74

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap FBXL18 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →