| Evidence type | Key finding | Experimental system/cohort | Quantitative/statistical details | Source (first author year, journal) | Publication date (month/year) | URL |
|---|---|---|---|---|---|---|
| RNAi screen / functional follow-up | FBXO36 was identified as a candidate regulator of TNF-dependent NF-κB nuclear accumulation; knockdown increased nuclear NF-κB at 120 min after TNF in secondary validation, and follow-up assays suggested enhanced TNF pathway signaling rather than a clear block in I-κB degradation. | High-content siRNA screen in HeLa cells with validation in A549 cells; orthogonal assays included qPCR and Western blotting for I-κB and phospho-JNK. | Primary/validation hit at 120 min TNF; at least 2 non-overlapping siRNAs supported the phenotype; knockdown caused persistent late-stage I-κB phosphorylation and moderate prolonged JNK phosphorylation; study-wide false discovery rate reported as 0.501; one-way ANOVA used vs non-silencing controls, but no FBXO36-specific fold change reported (pqac-00000002, pqac-00000003). | Fraser 2014, *Frontiers in Immunology* | Jul 2014 | https://doi.org/10.3389/fimmu.2014.00322 |
| RNAi screen / apoptosis follow-up | Loss of FBXO36 enhanced TNF + cycloheximide-induced apoptosis, consistent with altered TNF signaling output. | HeLa cell apoptosis follow-up after siRNA depletion; TUNEL-based assay. | Increased apoptosis particularly at early time points (2 h and 4 h noted in figure summary); no gene-specific fold change or p-value reported in extracted text (pqac-00000001, pqac-00000012). | Fraser 2014, *Frontiers in Immunology* | Jul 2014 | https://doi.org/10.3389/fimmu.2014.00322 |
| Functional inference / pathway context | FBXO36 depletion increased steady-state β-catenin levels, which the authors interpreted as supporting a possible role as a modifier of the SCF–βTrCP E3 ligase axis and thereby a potential link to I-κB ubiquitylation/NF-κB signaling. | Cell-based siRNA depletion in the Fraser TNF-signaling study. | Qualitative effect reported; no substrate of FBXO36 was directly validated and no numerical effect size was provided (pqac-00000001). | Fraser 2014, *Frontiers in Immunology* | Jul 2014 | https://doi.org/10.3389/fimmu.2014.00322 |
| Review / expression evidence | A 2024 review of F-box proteins in spermatogenesis lists FBXO36 among F-box genes expressed at high levels in testis, suggesting possible relevance to spermatogenesis, but gives no direct function, substrate, or infertility mechanism for FBXO36. | Review synthesis of F-box protein literature/expression data. | Expression-level note only; no mechanistic or statistical detail reported for FBXO36 in the extracted review text (pqac-00000004). | Xuan 2024, *Cell Regeneration* | Jun 2024 | https://doi.org/10.1186/s13619-024-00196-9 |
| Genetics / metabolomics association | Rare-variant gene-based analysis linked FBXO36 to circulating lipid metabolite variation, specifically IDL-CE% (cholesterol esters to total lipids ratio in IDL), representing a putative novel link between FBXO36 and lipid metabolism. | Sequencing-based metabolomics study of 7,142 participants measuring 226 serum lipoproteins, lipids, and amino acids. | Meta-analysis p = 1.98×10^-6 for IDL-CE% in MCAP+LoF analysis; WES: 5 variants, allele count 62, p = 1.62×10^-5; WGS: 2 variants, allele count 43, p = 2.56×10^-2; signal marked as driven by a single variant after conditioning; meets standard gene-level threshold p < 2.5×10^-6 but not stricter phenotype-adjusted threshold p < 1.32×10^-7 (pqac-00000005, pqac-00000008). | Riveros-McKay 2020, *PLOS Genetics* | Mar 2020 | https://doi.org/10.1371/journal.pgen.1008605 |
| Genetics / interpretation note | Authors explicitly noted that FBXO36 had no obvious prior link to lipid metabolism beyond being an F-box family member involved in protein ubiquitination, and that replication would be needed to establish the association. | Same 7,142-participant sequencing/metabolomics study. | Reported as a novel association at lower stringency threshold p < 2.5×10^-6; replication recommended (pqac-00000007, pqac-00000009). | Riveros-McKay 2020, *PLOS Genetics* | Mar 2020 | https://doi.org/10.1371/journal.pgen.1008605 |
| Cancer association / prognosis | In TP53-mutant lung adenocarcinoma, higher FBXO36 expression was reported to correlate with better survival outcome in DEG-based survival analysis. | TCGA lung adenocarcinoma dataset; 469 LUAD samples divided into TP53-wild-type and TP53-mutant groups; analyses also incorporated tumor mutation burden and immune infiltration. | Statement reported qualitatively; extracted text did not provide FBXO36-specific hazard ratio, median survival, or AUC; fragmentary figure text suggests significance at P < 0.05 but does not allow reliable extraction of a complete statistic (pqac-00000010, pqac-00000011). | Fu 2021, *Translational Cancer Research* | Sep 2021 | https://doi.org/10.21037/tcr-21-565 |
| OpenTargets association | Open Targets lists FBXO36 disease associations, but current evidence appears indirect/sparse and largely derives from aggregated genetics/functional-screen resources rather than FBXO36-focused mechanistic studies. | Open Targets platform aggregation for target ENSG00000153832 / FBXO36. | Example overall association scores: neurodegenerative disease 0.5331; hypertrophic cardiomyopathy 0.2942; sarcoidosis 0.2691; diabetes mellitus 0.1478; MRSA infection 0.1139. Evidence count shown as 5 for each listed disease in the retrieved record (pqac-00000000). | Open Targets platform entry for FBXO36 | Accessed 2026 | https://platform.opentargets.org/target/ENSG00000153832 |
| Overall evidence gap | Across the retrieved literature, no direct endogenous substrate, catalytic reaction, or definitive subcellular localization for human FBXO36 was experimentally established; current understanding is dominated by inference from its F-box domain and limited perturbation/association data. | Cross-source synthesis of available direct evidence for human FBXO36. | Evidence is sparse and mostly indirect; strongest direct functional data come from a 2014 TNF/NF-κB RNAi study, while later data are expression or association based (pqac-00000001, pqac-00000004, pqac-00000005, pqac-00000010). | Cross-source synthesis | 2014-2024 | Multiple URLs above |


*Table: This table compiles the most directly relevant evidence located for human FBXO36/Q8NEA4, spanning functional RNAi data, expression review evidence, human genetics/metabolomics associations, cancer prognosis associations, and Open Targets disease links. It is useful because the published literature on FBXO36 is sparse and fragmented, so the table highlights both what is known and the major evidence gaps.*