| Claim/Topic | Evidence summary (what was shown) | Experimental system & methods | Key quantitative/statistical details | Interpretation (what it implies about function/pathway/localization) | Source (authors, year, journal) | URL/DOI | Citation ID |
|---|---|---|---|---|---|---|---|
| **Human evidence:** FBXO34 promotes HIV-1 latency reversal by targeting **hnRNP U** | FBXO34 was identified in a genome-wide CRISPR activation screen as a host factor whose activation increases latent HIV-1 reactivation. Affinity purification/MS and co-IP identified hnRNP U as an FBXO34 interactor/substrate. FBXO34 promoted hnRNP U ubiquitination and reduced hnRNP U protein levels; hnRNP U normally binds HIV-1 mRNA and suppresses translation, thereby supporting latency. | Human latent HIV-1 cell models (C11, J-Lat 10.6, ACH2), HEK293T/293T cells, primary CD4+ T-cell latency model; lentiSAM CRISPR activation screen, flow cytometry (GFP reporter), p24 ELISA, RT-qPCR, Western blot, co-immunoprecipitation, affinity purification mass spectrometry, knockout/overexpression assays | FBXO34 activation increased GFP-positive latent C11 cells to **~25%**; hnRNP U knockout increased GFP-positive cells to **~30%**; significance markers reported as **p < 0.01** and **p < 0.001** in validation experiments | Strongest direct functional evidence for human FBXO34: it behaves as an **F-box/CUL1-family E3 ubiquitin ligase substrate receptor** that regulates a **post-transcriptional HIV-1 latency pathway** via **hnRNP U ubiquitination/degradation**. Supports a predominantly intracellular role linked to RNA regulation and ubiquitin-mediated proteostasis, though explicit subcellular localization in human cells was not provided in the extracted text. | Yang et al., 2022, *Emerging Microbes & Infections* | https://doi.org/10.1080/22221751.2022.2140605 | (pqac-00000004, pqac-00000005, pqac-00000006, pqac-00000012, pqac-00000013, pqac-00000014) |
| **Non-human evidence (mouse):** FBXO34 regulates meiotic G2/M transition and anaphase entry | Depletion of Fbxo34 in mouse oocytes caused failure of meiotic resumption due to low MPF activity; exogenous CCNB1 rescued the phenotype. Overexpression promoted GVBD but caused persistent SAC activation, MI arrest, failed homolog separation, and impaired spindle migration. | Mouse oocytes; mRNA microinjection, overexpression/depletion, live-cell imaging, chromosome spreading, localization by tagged protein imaging | Quantitative effect sizes were not extracted here, but rescue by **CCNB1** and opposing loss-/gain-of-function phenotypes were reported | Supports conserved biology for FBXO34 as an **SCF-type F-box regulator of cell-cycle control**, likely acting upstream of **CCNB1/CDK1/MPF** and checkpoint progression. This is informative for function but is **not direct human evidence**. | Zhao et al., 2021, *Frontiers in Cell and Developmental Biology* | https://doi.org/10.3389/fcell.2021.647103 | (pqac-00000001, pqac-00000009) |
| **Non-human evidence (mouse):** subcellular localization during oocyte maturation | In mouse oocytes, FBXO34 was reported to localize mainly in the **nucleus** and to **colocalize with F-actin** during meiotic maturation. | Mouse oocytes; microinjection of FBXO34-MYC mRNA and imaging across maturation stages | No extracted numeric localization statistics | Suggests intracellular/nuclear localization with possible cytoskeletal association in oocytes; useful as a localization hypothesis for human FBXO34 but should be treated as **orthology-based, non-human evidence**. | Zhao et al., 2021, *Frontiers in Cell and Developmental Biology* | https://doi.org/10.3389/fcell.2021.647103 | (pqac-00000009) |
| **Review/context (non-primary):** FBXO34 in oogenesis/SCF biology | Review summarizes Zhao et al. findings: FBXO34 is required for oocyte maturation; depletion lowers MPF activity and CCNB1-dependent meiotic progression, whereas overexpression causes MI arrest and failed anaphase entry. Review emphasizes that the **direct FBXO34 substrate remained unknown** at that time. | Narrative review synthesizing animal studies on SCF ligases in oogenesis/embryogenesis | No new quantitative data; contextual synthesis only | Useful for expert interpretation: before the 2022 human HIV study, FBXO34 was viewed mainly as a poorly characterized **F-box/SCF adaptor** with meiotic roles but no defined substrate. This helps place the hnRNP U finding in context. | Kinterová et al., 2022, *Cells* | https://doi.org/10.3390/cells11020234 | (pqac-00000002, pqac-00000003) |
| **Database inference (human genetics):** disease/trait associations from GWAS credible sets | Open Targets lists FBXO34 associations to multiple human disease/trait terms based on GWAS credible-set evidence, citing literature PMID **39024449**. Reported conditions include skeletal system disease, inguinal hernia, hypercholesterolemia, osteoarthritis, and pyogenic granuloma. | Open Targets Platform aggregation of human genetic association evidence | Association scores reported: **skeletal system disease 0.1573**, **inguinal hernia 0.0591**, **hypercholesterolemia 0.1712**, **osteoarthritis 0.0497**, **pyogenic granuloma 0.1813**; evidence resource scores **0.4906** and **0.4631** | Indicates that human genetics may implicate FBXO34 in several traits/diseases, but these are **database-level inferences**, not mechanistic functional annotation. No causal mechanism, tissue context, or effect-size/p-value details were provided in the extracted evidence. | Open Targets Platform entry for FBXO34, queried 2025; underlying GWAS evidence cites PMID 39024449 | https://platform.opentargets.org/target/ENSG00000178974 | (pqac-00000008, pqac-00000000) |
| **Current evidence gap / expert synthesis** | Across the retrieved literature, **hnRNP U** is the only clearly identified substrate/target of human FBXO34 with direct mechanistic support. No extracted evidence explicitly named canonical SCF components (e.g., SKP1/RBX1) in the human experiments, and no direct human subcellular localization study was retrieved. | Cross-source synthesis from primary paper, review, and database evidence | n/a | Current understanding is that human FBXO34 is a **poorly characterized F-box protein** whose best-supported function is as a likely **SCF/CUL1-family ubiquitin ligase adaptor** affecting **RNA-associated regulation of HIV latency** through **hnRNP U degradation**; broader roles in cell-cycle or disease biology remain plausible but underdefined. | Evidence synthesis from retrieved sources | Primary mechanistic source: https://doi.org/10.1080/22221751.2022.2140605 | (pqac-00000004, pqac-00000005, pqac-00000006, pqac-00000001, pqac-00000002, pqac-00000008) |


*Table: This table summarizes the strongest available evidence for functional annotation of human FBXO34 (UniProt Q9NWN3), distinguishing direct human mechanistic data from mouse orthology evidence and database-level genetic associations. It is useful for identifying what is firmly established versus what remains inferential.*