| Functional aspect | Key findings | Evidence type | System/Context | Citation ID(s) |
|---|---|---|---|---|
| SCF substrate receptor in glycoprotein quality control | FBXO6/FBS2 is described as part of an SCF ubiquitin ligase that ubiquitinates N-glycoproteins and participates in glycoprotein quality control linked to ER-associated degradation. | Review synthesis of prior biochemical/cell studies | NGLY1/ERAD pathway | (pqac-00000000, pqac-00000001) |
| ERAD glycoprotein ubiquitination | In NGLY1-deficient settings, SCF^FBS2-ubiquitinated N-glycoproteins accumulate in the cytosol and are associated with impaired proteasomal activity. | Cell-based observations summarized in review | NGLY1-deficient cells/models | (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000003) |
| NFE2L1 regulation | SCF^FBS2 ubiquitinates NFE2L1; in the absence of NGLY1 this impairs NFE2L1 processing/nuclear function and blocks proteasome subunit upregulation under proteotoxic stress. | Review synthesis of mechanistic and cell-based findings | NGLY1 deficiency and proteasome bounce-back pathway | (pqac-00000000, pqac-00000001) |
| Genetic modifier of NGLY1 deficiency | Reducing FBS2 dosage partially rescues lethality in Ngly1-knockout mice; Fbs2 deletion reportedly suppresses Ngly1-KO phenotypes more strongly than Engase deletion, while Fbs2-KO mice are described as otherwise healthy. | Mouse genetics | Rodent NGLY1-deficiency models | (pqac-00000000, pqac-00000002) |
| Candidate therapeutic target | Because FBS2 loss is phenotypically tolerated in mice and alleviates Ngly1-deficiency phenotypes, reviews suggest FBS2 inhibition as a potential therapeutic strategy for NGLY1 deficiency. | Expert review/analysis grounded in mouse genetics | Translational interpretation of NGLY1-deficiency models | (pqac-00000000, pqac-00000002) |
| Breast cancer prognostic marker | FBXO6 was one of four independent prognostic factors in an ER stress-related breast cancer model; protein expression was higher in breast cancer cell lines than in MCF-10A by Western blot, and FBXO6 expression reportedly did not significantly vary by stage. | Bioinformatics + Western blot | TCGA-BRCA ERScore model; SKBR-3, MDA-MB-231, T-47D vs MCF-10A | (pqac-00000006, pqac-00000011, pqac-00000012, pqac-00000013) |
| HCC prognostic/model gene | FBXO6 was included in a six-gene FBXO-family prognostic model for HCC; IHC showed higher expression of model genes in tumor vs adjacent tissue, including higher FBXO6 in invasive tumor specimens. Model AUCs were 0.744, 0.670, and 0.638 at 1, 3, and 5 years. | Bioinformatics + IHC | TCGA-LIHC prognostic model | (pqac-00000004, pqac-00000005, pqac-00000007, pqac-00000010) |
| HCC mechanism claims in literature vs current paper | The 2024 HCC study cites prior literature that FBXO6 promotes degradation of NLRX1 and Chk1, but its own FBXO6-related mechanistic claims are mainly predictive/associative (e.g., p53 docking/prediction) and the authors acknowledge lack of direct experimental validation. | Literature citation within paper + bioinformatics/IHC in current paper | HCC | (pqac-00000007, pqac-00000008, pqac-00000009) |


*Table: This table summarizes the directly supported functional annotation evidence retrieved for human FBXO6/Q9NRD1, separating mechanistic ERAD/NGLY1 findings from more associative cancer biomarker studies. It is useful for distinguishing well-supported core biology from newer, less validated disease-context observations.*