The protein encoded by FBXO11 is evolutionary conserved and is involved in phosphorylation-dependent ubiquitination, a cellular mechanism indispensable for adequate protein turnover. FBXO11 (also known as VIT1 and PRMT9) encodes the substrate-recognition component of the SCF (SKP1-cullin-F-box) complex, which is responsible for ubiquitination and subsequent degradation of substrates and plays a role in the maintenance of genome stability. FBXO11 is located on the short arm of chromosome 2, 2p16.3, g.47,789,316-47,905,793. Among its functional domains are the F-Box domain, three carbohydrate binding and hydrolase (CASH) domains and a zinc finger-UBR domain.
FBXO11 is expressed in various tissues, with high expression in the (fetal) brain.
Whole gene deletions, partial deletions, likely gene disrupting mutations and missense mutations were reported and the molecular mechanism of pathogenicity is likely haploinsufficiency although functional assays have not been performed.
In most individuals the mutation was heterozygous ‘de novo’ except for one homozygous variant described by Reuter et. al. Therefore, both dominant and recessive variants in FBXO11 might be pathogenic. Interestingly, in some individuals the mutation was found in only a percentage of lymphocytes. It is currently not clear to what extent these mosaic mutations contribute to the phenotype.
FBXO11