| Claim/topic | Evidence type | Key details/quantitative stats | Primary source | URL/DOI | Notes/limitations |
|---|---|---|---|---|---|
| FBXW9 identity as a human F-box/WD40 protein | Domain/family annotation supported by cancer-family analyses | FBXW9 is included among the 10 human FBXW proteins; FBXW family members contain an F-box domain plus multiple WD40 domains; FBXW9 length reported as 458 aa and localization as cytosol in UniProt/GeneCards-based family annotation (pqac-00000002, pqac-00000003, pqac-00000004) | Yu 2023, *Int J Mol Sci*; Huang 2024, *Front Immunol* | https://doi.org/10.3390/ijms24065262; https://doi.org/10.3389/fimmu.2022.1084339 | Strong for family/domain assignment; not a direct biochemical assay on Q5XUX1 alone |
| FBXW9 binds SKP1 | Experimental protein–protein interaction | Identified in array MAPPIT screen as a novel SKP1 interactor and validated by co-immunoprecipitation in HEK293T cells using E-tagged SKP1 bait and Flag-tagged FBXW9 prey (pqac-00000006, pqac-00000008) | Lievens 2009, *J Proteome Res* | https://doi.org/10.1021/pr8005167 | Direct interaction evidence supports SCF-type adaptor behavior; does not by itself prove substrate specificity or ubiquitination activity |
| FBXW9 associates with CUL1-containing SCF assemblies | AP-MS proteomics | Tandem-tagged CUL1 affinity purification in HEK293-derived cells recovered FBXW9 among 42 CUL1-associated F-box proteins; FBXW9 reported with ~61 spectral counts (pqac-00000007) | Lee 2011, *Mol Cell Proteomics* | https://doi.org/10.1074/mcp.m110.006460 | Co-purification is strong proteomic evidence for SCF association, but not an orthogonal FBXW9-specific co-IP |
| FBXW9 as a putative substrate receptor in CRL7 | Review-level mechanistic claim | Review states: “However, unlike SCF, Fbxw9 is the only known substrate receptor for CRL7,” in context of cullin-RING ligase architecture (pqac-00000014) | Jeong 2023, *Exp Mol Med* | https://doi.org/10.1038/s12276-023-01087-w | Useful expert summary, but secondary-source claim; underlying primary evidence was not recovered here. Note potential inconsistency within the review’s broader Cul7/Crl7 discussion (pqac-00000015) |
| Subcellular localization | Database/family annotation | Family-level analyses cite FBXW9 localization as “cytosol”; most FBXW members localize to cytoplasm/cytosol (pqac-00000001, pqac-00000004) | Huang 2024, *Front Immunol* | https://doi.org/10.3389/fimmu.2022.1084339 | Localization appears database-derived rather than from microscopy/fractionation experiments specific to FBXW9 |
| FBXW9 is a direct p53 target gene | Experimental transcriptional regulation | ChIP-seq/ChIP-qPCR showed p53 occupancy near Fbxw9 promoter; p53 increased luciferase reporter activity; p53 knockdown reduced expression; Nutlin-3 induced Fbxw9 in p53-WT but not p53-null human cells; tumors with WT p53 had higher FBXW9 mRNA than p53-mutant tumors (pqac-00000013) | Shin 2024, *Genes & Diseases* | https://doi.org/10.1016/j.gendis.2023.03.009 | Strong evidence that FBXW9 is p53-responsive; does not identify FBXW9 protein substrates |
| FBXW9 may regulate TP53/p21 axis in breast cancer | Mixed: prediction + perturbation experiment | UbiBrowser predicted 36 substrates with TP53 as hub; siRNA knockdown of FBXW9 in SUM159 and MDA-MB-231 cells increased p21 mRNA/protein and reduced CCNA2/CCNB1, consistent with G0/G1 arrest (pqac-00000009, pqac-00000010) | Yu 2023, *Int J Mol Sci* | https://doi.org/10.3390/ijms24065262 | TP53 as substrate remains predicted, not biochemically validated by ubiquitination/degradation assay |
| FBXW9 promotes breast cancer cell proliferation/cell-cycle progression | Experimental cell biology | siRNA-mediated FBXW9 silencing in SUM159 and MDA-MB-231 reduced proliferation and colony formation and induced G0/G1 arrest with fewer S-phase cells (pqac-00000010) | Yu 2023, *Int J Mol Sci* | https://doi.org/10.3390/ijms24065262 | Functional evidence in vitro; mechanism upstream/downstream of TP53 remains inferential |
| FBXW9 correlates with MYC activity, stemness, and immune features in breast cancer | Bioinformatic correlation + limited perturbation | FBXW9 positively correlated with MYC signaling and cancer stemness; knockdown repressed NECTIN2 and altered immune-related genes including CD274/PDCD1LG2; high FBXW9 associated with poorer outcome and poor prognosis under anti-PD1 treatment in analyzed cohorts (pqac-00000009, pqac-00000011) | Yu 2023, *Int J Mol Sci* | https://doi.org/10.3390/ijms24065262 | Mostly correlative/transcriptomic; no direct mechanistic link to immune evasion established |
| FBXW9 is downstream of IGFBP5–ROR1/HER2–CREB signaling in glioblastoma stem-like cells | Experimental pathway mapping | FBXW9 expression higher in invasive vs non-invasive GSCs; IGFBP5 overexpression increased, and IGFBP5 knockdown decreased, FBXW9; CREB ChIP-qPCR showed enrichment at FBXW9 locus and reduced binding after shIGFBP5; CREB overexpression rescued invasion suppressed by IGFBP5/HER2/ROR1 knockdown (pqac-00000016, pqac-00000017, pqac-00000018) | Lin 2023, *Nat Commun* | https://doi.org/10.1038/s41467-023-37306-1 | Strong pathway-position evidence, but does not show FBXW9 biochemical substrates |
| FBXW9 contributes to glioblastoma invasion | Experimental knockdown + clinical correlation | siRNA against FBXW9 significantly decreased invasion capacity in X01 and 448 GSC lines; high FBXW9 associated with worse glioma/LGG survival, including FBXW9 alone (P = 0.0005) and combined IGFBP5+FBXW9 signature (P = 0.00004) (pqac-00000017, pqac-00000018, pqac-00000024) | Lin 2023, *Nat Commun* | https://doi.org/10.1038/s41467-023-37306-1 | Invasion role is experimentally supported, but reported invasion quantification for direct FBXW9 knockdown is largely in supplementary figures |
| Upregulation and prognosis across cancers | Bioinformatic pan-cancer analysis | FBXW9 upregulated in many tumor types; family-level analyses implicate FBXW9 as detrimental in selected cancers and associated with immune infiltration/stromal features (pqac-00000001, pqac-00000003, pqac-00000011) | Yu 2023, *Int J Mol Sci*; Huang 2024, *Front Immunol* | https://doi.org/10.3390/ijms24065262; https://doi.org/10.3389/fimmu.2022.1084339 | Important for hypothesis generation and biomarker studies, but not direct function |
| Disease-target associations in Open Targets | Database association | Open Targets lists low-score associations for FBXW9 with oral mucosa leukoplakia, familial isolated congenital asplenia, X-linked retinal dysplasia, central areolar choroidal dystrophy, and familial exudative vitreoretinopathy (pqac-00000000) | Open Targets Platform | https://platform.opentargets.org/target/ENSG00000132004 | Evidence sizes were small and literature fields were empty in retrieved context; should not be overinterpreted |
| What is *not* yet established for human FBXW9 | Negative/uncertain evidence summary | No directly validated endogenous ubiquitination substrate for human FBXW9 was recovered; no direct catalytic assay, no substrate degron definition, and no definitive microscopy-based localization were found in retrieved literature (pqac-00000005, pqac-00000009, pqac-00000010) | Synthesis from available sources | N/A | The literature supports FBXW9 as an F-box substrate-recognition protein with cancer-related functions, but its precise biochemical substrate repertoire remains largely unresolved |
| FBXW9 as a stable-expression reference gene in hematologic malignancy qPCR | Experimental application, not mechanism | In a qPCR normalization study across 78 samples, PTCD2, PPP1R3B, and FBXW9 were among the most stable low-variance genes selected as candidate reference genes; FBXW9 primer set targeted NM_032301 (pqac-00000022, pqac-00000023) | Dwivedi 2020, *PLoS One* | https://doi.org/10.1371/journal.pone.0236338 | Useful real-world implementation for assay design; does not illuminate FBXW9 molecular function |
| Expert consensus framing | Review/expert analysis | Reviews describe FBXW proteins as substrate-recognition subunits of SCF E3 ligases that use F-box domains to assemble into SCF complexes and WD40 repeats to bind substrates; FBXW9 is repeatedly highlighted as poorly characterized compared with FBXW1/FBXW7 (pqac-00000002, pqac-00000005, pqac-00000014) | Yu 2023, *Int J Mol Sci*; Jeong 2023, *Exp Mol Med* | https://doi.org/10.3390/ijms24065262; https://doi.org/10.1038/s12276-023-01087-w | Good high-level context; for FBXW9 specifically, many claims remain extrapolated from family behavior rather than direct primary evidence |


*Table: This table separates experimentally supported findings from predictions and database associations for human FBXW9 (Q5XUX1). It is useful for quickly distinguishing what is known with direct evidence versus what remains inferred or weakly supported.*