FBXO40

Chr 3

F-box protein 40

Also known as: FBX40

NCBI Gene: 51725 ENSG00000163833 UniProt: Q9UH90 OMIM: 609107

The FBXO40 protein functions as a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes that may be involved in muscle development. Mutations in FBXO40 cause autosomal recessive intellectual disability with seizures and language delay. This gene is not highly constrained against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq, UniProt

Members of the F-box protein family, such as FBXO40, 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]

OMIM ResearchGenerating clinical summary…

LOEUF 1.08

Clinical Summary— FBXO40

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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

100 VUS of 109 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?

1.08LOEUF

pLI 0.000

Z-score 1.26

OE 0.71 (0.48–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.22Z-score

OE missense 0.97 (0.89–1.05)

376 obs / 388.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.71 (0.48–1.08)

0≤0.351.4

Missense OE?0.97 (0.89–1.05)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 16 / 22.5Missense obs/exp: 376 / 388.0Syn Z: -0.07

ClinVar Variant Classifications

109 submitted variants in ClinVar

ClinVar

Classification Summary

VUS100

Likely Benign7

100

VUS

Likely 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	100	0	100
Likely Benign	5	2	7
Benign	0	0	0
Total	105	2	107

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap FBXO40 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →