FBXO22

Chr 15AR

F-box protein 22

Also known as: FBX22, FISTC1, TYMAS

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.301 OMIM phenotype
Clinical SummaryFBXO22
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.977
Z-score 3.48
OE 0.06 (0.020.30)
Highly constrained

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

Missense Constraint
0.84Z-score
OE missense 0.84 (0.750.95)
188 obs / 223.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.06 (0.020.30)
00.351.4
Missense OE0.84 (0.750.95)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 1 / 16.0Missense obs/exp: 188 / 223.2Syn Z: -0.60
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FBXO22 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

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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