| Evidence type | Key finding | System/assay | Quantitative/statistical detail | Source (authors, year, journal) | URL/DOI | Notes/limitations |
|---|---|---|---|---|---|---|
| Domain/complex | Human FBXW10 is identified as UniProt Q5XX13, a 1052-aa F-box/WD-repeat protein annotated as an “E3 CRL adaptor,” consistent with an SCF-type substrate receptor architecture. (pqac-00000001) | Proteome/interactome annotation table | Length reported as 1052 aa; row annotated with F-box domain and WD repeats. (pqac-00000001) | Poirson et al., 2017, *The FEBS Journal* | https://doi.org/10.1111/febs.14193 | Classification/annotation evidence rather than direct biochemical demonstration of SCF assembly or substrate binding. |
| Substrate/function | Lamin A rod-domain mutants induce FBXW10, and ectopic FBXW10 is sufficient to deplete HP1α and HP1β, but not HP1γ, supporting a role in selective ubiquitin-proteasome-mediated turnover of HP1 isoforms. (pqac-00000000, pqac-00000012) | HeLa cell expression studies; immunofluorescence; western blot; qRT-PCR | FBXW10 qRT-PCR: GFP 1.71 ± 0.43, WT lamin A 1.66 ± 0.70, G232E 5.64 ± 0.49, R386K 2.35 ± 0.44; ectopic FBXW10 depleted HP1α/β in 80–90% of cells. (pqac-00000012) | Chaturvedi & Parnaik, 2010, *PLoS ONE* | https://doi.org/10.1371/journal.pone.0010620 | Evidence is from overexpression/mutant-lamin context; direct ubiquitination of HP1 by purified SCF-FBXW10 was not shown. |
| Substrate/rescue | HP1α/β loss in lamin-mutant cells is proteasome-dependent, and proteasome inhibition restores HP1 and partially rescues lamin/emerin nuclear-rim localization, linking FBXW10-associated phenotype to proteasomal degradation. (pqac-00000000, pqac-00000012, pqac-00000016) | HeLa cells treated with MG132 or lactacystin; immunofluorescence; western blot | MG132 restored G232E rim localization from 19.6% ± 6.09 to 83.2% ± 6.11 and R386K from 15.4% ± 5.11 to 61.0% ± 6.40; lactacystin restored G232E to 73.2% ± 9.07 and R386K to 39.8% ± 8.57; HP1-positive cells also increased markedly with inhibitors. (pqac-00000012, pqac-00000016) | Chaturvedi & Parnaik, 2010, *PLoS ONE* | https://doi.org/10.1371/journal.pone.0010620 | Rescue implicates the proteasome but does not by itself prove FBXW10 is the only E3 responsible. |
| Disease/genetics | FBXW10 has been reported mutated in T-cell prolymphocytic leukemia (T-PLL), supporting possible disease relevance of loss/alteration of function. (pqac-00000002) | Literature review of hematologic malignancy genetics | Reported variants include missense, nonsense, and frameshift changes such as R318N, R416*, and K966fs. (pqac-00000002) | Sahasrabuddhe & Elenitoba-Johnson, 2015, *Immunological Reviews* | https://doi.org/10.1111/imr.12236 | Review explicitly states that very little is known about FBXW10 biology and substrates; mutation significance remains uncertain. |
| Disease/variant interpretation | In familial non-medullary thyroid cancer (FNMTC), FBXW10 was nominated as a candidate susceptibility gene carrying a heterozygous in-frame deletion p.Ile440del. (pqac-00000005, pqac-00000006) | Whole-exome sequencing and pedigree segregation analysis | Variant: c.1317_1319delCAT; p.Ile440del; chr17:18661699; segregated in heterozygous state in multiple family members with incomplete penetrance. (pqac-00000005, pqac-00000006) | Majdalani et al., 2023, *International Journal of Molecular Sciences* | https://doi.org/10.3390/ijms24098233 | Candidate-gene evidence only; authors prioritized ARHGEF28 over FBXW10 as the strongest causal candidate. |
| Domain/structure | The p.Ile440del candidate variant lies in the WD-repeat propeller region, where structural modeling predicts disruption of a beta-hairpin within a propeller blade. (pqac-00000005) | Conservation analysis and AlphaFold-based structural interpretation | Ile440 conserved down to placental mammals; AlphaFold model around site reported with pLDDT > 90; ACMG evidence listed as PM2, PM4. (pqac-00000005) | Majdalani et al., 2023, *International Journal of Molecular Sciences* | https://doi.org/10.3390/ijms24098233 | Inference is structural/computational, not functional validation in cells or animals. |
| Expression/cancer association | FBXW10 shows differential expression across cancers in pan-cancer analysis, with higher expression in several tumor types and lower expression in some kidney cancers and thyroid cancer. (pqac-00000004) | TCGA-based pan-cancer expression analysis | Higher in LUAD, LUSC, LIHC, PRAD, STAD; reduced in KICH, KIRC, THCA versus normal tissues. (pqac-00000004) | Huang et al., 2024, *Frontiers in Immunology* | https://doi.org/10.3389/fimmu.2022.1084339 | Expression correlations do not establish mechanism, substrate specificity, or causal function in these cancers. |


*Table: This table summarizes the main published evidence supporting functional annotation of human FBXW10/Q5XX13, including domain architecture, experimentally supported substrate-linked effects, disease-associated variants, and cancer-expression findings. It is useful for distinguishing direct evidence from inference and highlighting the major limitations of the current literature.*