| Evidence type | Molecular role | Validated substrates | Pathway/process | Subcellular localization | Key quantitative findings | Diseases/phenotypes | Primary reference (year) | DOI URL |
|---|---|---|---|---|---|---|---|---|
| Human; in vitro (HEK293, NT2/D1), human fetal tissue | F-box protein functioning as E3 ubiquitin ligase/SCF-type substrate adaptor for proteasomal turnover | RARγ | RA/RARγ-BMP signaling; positive regulation of BMP signaling via RARγ degradation | Predominantly cytoplasmic; cytoplasmic colocalization with RARγ; domains mapped: zinc finger aa48-109, F-box aa373-409 | RARγ half-life ~4 h; FBXO30 knockdown RNA-seq: 86 upregulated and 78 downregulated genes; positive correlation with ID2 r=0.672 (p<0.05); negative correlation with chordin r=-0.515 (p<0.05); NanoString n=10; some WB n=3; human NTD retinoid values reported up to ~9.31 ng/mg in anencephaly vs up to ~3.70 ng/mg in controls (pqac-00000001, pqac-00000012, pqac-00000013, pqac-00000015) | Neural tube defects; aberrant FBXO30 levels/downregulation in high-retinol NTD samples; reduced BMP target gene expression (pqac-00000005, pqac-00000012, pqac-00000013) | Cheng et al. (2019) (pqac-00000005, pqac-00000012) | https://doi.org/10.1038/s41419-019-1783-y |
| Human; in vitro and in vivo (ccRCC cell lines, xenograft/metastasis models), human tumor cohorts | F-box protein in SCF-type E3 ligase complexes; tumor-suppressive E3 ligase promoting proteasome-dependent HIF-1α degradation in hZIP1/Zn2+-dependent axis | HIF-1α | Hypoxia/HIF-1α regulation; hZIP1/Zn2+/FBXO30/HIF-1α axis | Not established in gathered 2023 ccRCC evidence | TCGA analyses used 533 ccRCC vs 72 adjacent normal tissues in one report; another excerpt reports 253 renal cancer tissues vs 72 normal tissues; clinical validation included 20 paired tumors for WB and 24 paired tumors for RT-qPCR; xenograft n=5/group; lung metastasis assay n=3/group; higher FBXO30 associated with better overall survival using 50% cutoff (pqac-00000009, pqac-00000010, pqac-00000011) | Clear cell renal cell carcinoma; FBXO30 downregulated with higher grade/stage; FBXO30 overexpression suppresses proliferation, invasion, EMT, tumorigenesis, metastasis (pqac-00000009, pqac-00000010) | Yuan et al. (2023) (pqac-00000009, pqac-00000010, pqac-00000011) | https://doi.org/10.3892/ijo.2023.5488 |
| Mouse; in vivo mammary gland plus biochemical/cell-based assays | SCF adaptor/E3 ligase component; binds SKP1 and CUL1 and ubiquitinates substrate | Eg5/KIF11 | Mitosis, centrosome homeostasis, spindle assembly, mammopoiesis | Not established in gathered excerpts | Mass spectrometry identified 7 unique EG5 peptides; co-IP recovered EG5, SKP1, CUL1; Eg5-binding region mapped to C-terminus likely aa812-1052; rescue of Fbxo30-/- defects by shRNA or EG5 inhibitor demonstrated functional specificity (pqac-00000002, pqac-00000003, pqac-00000006) | Mammary gland developmental defects; impaired mammary stem/progenitor function; centrosome and spindle abnormalities when Fbxo30 lost (pqac-00000002, pqac-00000006) | Liu et al. (2016) (pqac-00000002, pqac-00000003, pqac-00000006) | https://doi.org/10.1016/j.celrep.2016.03.083 |
| Mouse; oocyte RNAi, proteomics, immunofluorescence, transfected cells | F-box protein/SCF-family substrate selector promoting ubiquitin-proteasome turnover | SLBP | Oocyte meiosis; chromosome condensation/segregation via SLBP-histone H3 control | Nuclear at GV; cytoplasmic after GVBD with enrichment around chromosomes; spindle-associated at Pro-MI/MI; minimal at MII (pqac-00000004, pqac-00000008) | iTRAQ used 3000 MI oocytes/group; 238 Fbxo30-associated proteins identified; 13 unique SLBP peptides detected; MG132 4 μM for 6 h used in ubiquitination/proteasome assays (pqac-00000004, pqac-00000007) | Meiotic arrest, failure of polar body extrusion, chromosome overcondensation and segregation defects after Fbxo30 depletion; rescue by SLBP knockdown (pqac-00000004, pqac-00000007, pqac-00000008) | Jin et al. (2019) (pqac-00000004, pqac-00000007, pqac-00000008) | https://doi.org/10.1007/s00018-019-03038-z |
| Cross-source synthesis: human primary evidence plus mouse functional orthology | Overall current annotation: substrate-recognition F-box protein in SCF/CUL1-RING ubiquitin ligase complexes, with context-dependent substrates rather than enzymatic small-molecule catalysis | Human: RARγ, HIF-1α; Mouse: Eg5/KIF11, SLBP | Developmental signaling (RA/BMP), hypoxia signaling, mitotic control, chromosome segregation | Context-dependent; cytoplasmic in human RARγ study; spindle/chromosome-associated in mouse oocytes (pqac-00000001, pqac-00000004, pqac-00000008) | Recent review notes many F-box proteins in spermatogenesis remain incompletely defined; for FBXO30, mechanistic evidence is still substrate- and tissue-specific rather than system-wide (pqac-00000000) | Disease links supported in Open Targets include neural tube defect and nonpapillary renal cell carcinoma, but evidence base is limited and literature-driven rather than genetically definitive (pqac-00000000) | Open Targets / literature-supported synthesis (2024 update context) (pqac-00000000) | https://platform.opentargets.org/target/ENSG00000118496 |


*Table: This table summarizes experimentally supported functional annotation for human FBXO30 (UniProt Q8TB52) and the most relevant orthologous mouse evidence. It organizes validated substrates, pathways, localization, quantitative findings, and disease links so the evidence base can be assessed at a glance.*