FBXO22

Chr 15q24.2

F-box protein 22

Aliases:: FBX22, FISTC1
MANE:: ENST00000308275.8

OMIM: 609096 ↗NCBI: 26263 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

FBXO22 · Q8NEZ5

v62025-08-01

Predicted Aligned Error matrix for FBXO22 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

86.3/ 100

Confident

403 residues

Confidence breakdown

Very high(≥ 90)65%
Confident(70–90)22%
Low(50–70)7%
Very low(< 50)6%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Monogenic short stature
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Tayoun-Maawali syndrome
0.60
neurodegenerative disease
0.52
neurodevelopmental disorder
0.34
gout
0.34
preeclampsia
0.31
diabetes mellitus
0.24
kidney failure
0.11
neoplasm
0.10
hepatocellular carcinoma
0.10
lung cancer
0.10

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

F-box only protein 22

Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that is implicated in the control of various cellular processes such as cell cycle control, transcriptional regulation, DNA damage repair, and apoptosis. Promotes the proteasome-dependent degradation of key sarcomeric proteins, such as alpha-actinin (ACTN2) and filamin-C (FLNC), essential for maintenance of normal contractile function. Acts as a key regulator of histone methylation marks namely H3K9 and H3K36 methylation through the regulation of histone demethylase KDM4A protein levels (PubMed:21768309). In complex with KDM4A, also regulates the abundance of TP53 by targeting methylated TP53 for degradation at the late senescent stage (PubMed:26868148). Under oxidative stress, promotes the ubiquitination and degradation of BACH1. Mechanistically, reactive oxygen species (ROS) covalently modify cysteine residues on the bZIP domain of BACH1, leading to its release from chromatin and making it accessible to FBXO22 (PubMed:39504958). Upon amino acid depletion, mediates 'Lys-27'-linked ubiquitination of MTOR and thereby inhibits substrate recruitment to mTORC1 (PubMed:37979583). Also inhibits SARS-CoV-2 replication by inducing NSP5 degradation (PubMed:39223933)