FBXO22

Chr 15

F-box protein 22

Also known as: FBX22, FISTC1, TYMAS

NCBI Gene: 26263 ENSG00000167196 UniProt: Q8NEZ5

The protein functions as a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes, promoting proteasomal degradation of key sarcomeric proteins including alpha-actinin and filamin-C, and regulating histone methylation through control of histone demethylase levels. Mutations cause Tayoun-Maawali syndrome with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variation (pLI 0.98, LOEUF 0.30), indicating that biallelic variants are likely to have significant clinical impact.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and, as a transcriptional target of the tumor protein p53, is thought to be involved in degradation of specific proteins in response to p53 induction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.30

Clinical Summary— FBXO22

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 45 VUS of 62 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?

0.30LOEUF

pLI 0.977

Z-score 3.48

OE 0.06 (0.02–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.84Z-score

OE missense 0.84 (0.75–0.95)

188 obs / 223.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.30)

0≤0.351.4

Missense OE?0.84 (0.75–0.95)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 1 / 16.0Missense obs/exp: 188 / 223.2Syn Z: -0.60

This gene — mechanism propensity

0.2399th %ile

GOF

0.2597th %ile

LOF

0.66top 25%

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

LOFprediction above median · LOEUF 0.30

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

62 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

VUS45

Likely Benign2

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	3	0	1	4
Likely Pathogenic	0	0	0	0
VUS	0	45	0	45
Likely Benign	0	2	0	2
Benign	0	0	0	0
Total	3	47	1	51

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap FBXO22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →