| Aspect | FBXO41-specific finding | Evidence type | Organism/system | Key quantitative/statistical notes | Citations |
|---|---|---|---|---|---|
| Identity verification | Target matches **human FBXO41 / F-box only protein 41**, UniProt **Q8TF61**; reported as an **875-aa F-box protein** with higher expression in nervous system, helping distinguish it from unrelated FBX genes | Human genetic / bioinformatic annotation | Human | Gregianin reports FBXO41 as 1 of 46 F-box family members; transcript/protein identifiers linked to human FBXO41 | (pqac-00000005, pqac-00000008) |
| Domain architecture | Canonical **F-box domain** in the C-terminal half supports SCF-type adaptor role; literature also reports an N-terminal **apolipophorin III-like** region, while newer domain resources/UniProt list F-box-like and LRR-related signatures | Bioinformatic / domain inference | Human | Domain inference used to support ubiquitin-ligase adaptor hypothesis; N-terminal structure remained poorly templated in 2014 analysis | (pqac-00000005, pqac-00000008) |
| Proposed molecular function | FBXO41 behaves as an **SCF/CRL substrate adaptor**: associates with **SKP1** and **CUL1**; deletion or mutation of the F-box abolishes these interactions | Cell biology / biochemical interaction | Mouse protein in neuronal cells and hTERT-RPE1 model | FBXO41 assembles with SCF “less efficiently than Fbxo21”; **ΔF-box** or **W577A** disrupts SKP1/CUL1 binding | (pqac-00000001, pqac-00000004) |
| Alternative ligase complex model | Separate mouse work proposes a **FBXO41–CUL7** E3 ligase complex in CNS neurons, implying FBXO41 may not be limited to canonical CRL1/SCF usage | Mouse functional study / thesis-level evidence | Mouse cerebellar granule neurons | Evidence is mechanistic but less independently validated than SCF/CUL1 data | (pqac-00000002, pqac-00000007) |
| Subcellular localization | FBXO41 is **cytoplasmic**, excluded from nucleus, with a strong **centrosomal/pericentriolar/centriole** pool in neurons | Mouse knockout / cell biology | Mouse neurons | Colocalizes with **pericentrin**; endogenous FBXO41 recovered in centrosome-enriched fraction | (pqac-00000004, pqac-00000006) |
| Cell-type/tissue expression | FBXO41 is **neuron-enriched/CNS-selective** rather than broadly glial; expression rises during brain development and is abundant postnatally in cerebellum | Expression profiling | Mouse; human inference from genetics | Detectable from **E10** in mouse; not expressed in astrocytes or oligodendrocytes in cited mouse studies | (pqac-00000004, pqac-00000006) |
| Biological process: neuronal migration | FBXO41 is required for proper **cerebellar granule neuron migration**; loss causes delayed migration and persistence of cells in inappropriate layers | Mouse knockout | Mouse | FBXO41-null mice show residual **external granule layer at P16** and increased cells in molecular layer; severe ataxia-like phenotype | (pqac-00000002, pqac-00000003) |
| Biological process: axon growth | Cytoplasmic FBXO41 promotes **axon growth** in cerebellar granule neurons; thesis work links this to non-proteolytic ubiquitination | Mouse neuronal culture / in vivo inference | Mouse | Proposed **K63-linked** ubiquitination of NFM stabilizes substrate and promotes axon extension | (pqac-00000002, pqac-00000007) |
| Biological process: primary cilia disassembly | Centrosomal FBXO41 promotes **neuronal primary cilia disassembly/shortening**; higher centrosomal FBXO41 correlates with shorter cilia | Cell culture overexpression | Mouse primary hippocampal neurons; hTERT-RPE1 cells | Overexpression reduced both **cilia length** and **% ciliated neurons**; infected at **DIV1→DIV15** or **DIV13→DIV21** with similar effect | (pqac-00000001, pqac-00000003, pqac-00000004) |
| Pathway impact: Sonic Hedgehog | By altering cilia structure, FBXO41 perturbs **Sonic hedgehog (Shh) signaling**, a canonical cilium-dependent pathway | Cell culture functional assay | Mouse neurons / hTERT-RPE1 cells | Cilia-disassembly phenotype depends on centrosomal targeting and SCF assembly competence | (pqac-00000001, pqac-00000004) |
| Mechanistic modifiers of cilia phenotype | FBXO41-dependent cilia disassembly requires **actin-cytoskeleton rearrangement**; **Aurora A kinase** requirement is seen in mitotic but not post-mitotic cells | Cell biology / pharmacology | Mouse neurons; hTERT-RPE1 cells | **Cytochalasin D** and Aurora A pathway manipulation rescue/prevent shortening in the relevant contexts; **PDBU** recruits overexpressed FBXO41 to centrioles | (pqac-00000001, pqac-00000004) |
| Known/putative partners and substrates | Reported partners/substrates include **SKP1**, **CUL1**, proposed **CUL7**, **DISC1**, possible **NDEL1**, and proposed substrate **NFM** | Biochemical interaction / mouse functional study | Mouse | Direct ubiquitination substrate identification remains limited; strongest replicated partners are SCF components SKP1/CUL1 | (pqac-00000002, pqac-00000004, pqac-00000007) |
| Human rare-disease genetics | A **homozygous c.950G>A (p.Arg317Gln)** FBXO41 variant segregated in an affected family and was absent in controls, supporting possible disease relevance but not definitive causality | Human genetic | Human | Variant absent from **400 control chromosomes**; predicted damaging by **PolyPhen2 ~0.99**, **MutationTaster ~0.99**, **GERP++ 5.17**; **SIFT 0.15** reported tolerated | (pqac-00000005, pqac-00000008) |
| Phenotype association from animal model | FBXO41 loss causes **early mortality, severe ataxia-like gait, cerebellar migration defects, and neurodegeneration** | Mouse knockout | Mouse | Phenotypes reported around **P12–P30**, with strong motor abnormalities at **P16/P30** | (pqac-00000002, pqac-00000007) |
| Curated disease associations | Disease databases link FBXO41 to **cerebellar ataxia/dysequilibrium/dystonia-related terms**, largely traceable to literature around cerebellar phenotypes rather than established therapeutic targeting | Database curation / literature aggregation | Human | Open Targets evidence scores are modest; example diseases include generalized dystonia and infantile-onset autosomal recessive nonprogressive cerebellar ataxia | (pqac-00000000) |
| 2024 epigenetic development | In **22q11.2 deletion syndrome**, **FBXO41 showed 14 significant DMPs** and an **exon 2 DMR hypermethylated** in patients vs controls, placing FBXO41 among replicated episignature genes | Human epigenetics | Human blood in 22q11.2DS cohort | Comparison used **14 patients vs 14 controls**; 15 genes overlapped prior episignature, including FBXO41; enrichment p-value for replicated genes **1.12e-6** | (pqac-00000012, pqac-00000013) |
| 2024 cancer/biomarker signal | FBXO41 appears in some recent pan-gene or cancer bioinformatic analyses, but evidence is **indirect and not functionally validated** for FBXO41 itself | Bioinformatic association | Human cancer datasets | In KIRC-related panel analyses, high FBXO41 expression associated with worse OS in univariate analysis, but **not an independent predictor**; no FBXO41-specific HR given in excerpt | (pqac-00000009) |
| Evidence gaps / current understanding | No definitive catalytic activity, no validated small-molecule targeting, and no firmly established human substrate repertoire are currently available; best-supported role is as a **neuronal ubiquitin-ligase adaptor regulating centrosome/cilia and cerebellar development** | Synthesis of available evidence | Human with strong support from mouse/cell models | Strongest mechanistic evidence predates 2023; 2023–2024 updates are mainly epigenetic or bioinformatic rather than new core biochemistry | (pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000013) |


*Table: This table summarizes verified identity, domain architecture, molecular function, localization, biological roles, partners, and disease/epigenetic associations for human FBXO41 (UniProt Q8TF61). It highlights where evidence is strongest, especially mouse and cell-based studies, and where recent human findings remain associative rather than mechanistically definitive.*