| Evidence type | Finding | System/assay & sample size | Quantitative stats (AUC/p-value/etc.) | Source (include URL, year) | Context citation ID |
|---|---|---|---|---|---|
| Structure/domain | Human ISM2 (UniProt Q6H9L7) is a secreted ~63.9 kDa isthmin-family protein with an N-terminal signal peptide, a central thrombospondin type-1 repeat (TSR1), and a C-terminal AMOP domain. | Family/domain review synthesizing sequence/domain annotations for human ISM2. | ~63.9 kDa protein; no direct functional effect size reported. | Shakhawat HM et al., *Cells* (2022), https://doi.org/10.3390/cells12010017 | (pqac-00000002) |
| Localization | ISM2 is inferred to be extracellular/secreted; pregnancy-focused studies additionally describe it as highly placenta-associated and detectable in circulating microparticles/plasma. | Review/domain annotation; placental serum ELISA study; CMP plasma proteomics in pregnancy. | ELISA sensitivity ~5.0 pg/mL; assay CVs <15% in one study. | Shakhawat HM et al., *Cells* (2022), https://doi.org/10.3390/cells12010017; Martinez C et al., *Heliyon* (2020), https://doi.org/10.1016/j.heliyon.2020.e05096 | (pqac-00000002, pqac-00000006) |
| Molecular interaction/motif | ISM2 TSR1 contains WSPW and EPQ motifs; the AMOP domain contains a KGD motif reported to bind integrin αIIbβ3 and a WSRL motif proposed to participate in autophagy induction. Evidence is largely motif/domain-based rather than direct ISM2 biochemical validation. | Domain/motif analysis in review literature. | No ISM2-specific binding constant or cellular effect size reported. | Shakhawat HM et al., *Cells* (2022), https://doi.org/10.3390/cells12010017 | (pqac-00000001) |
| Pathway/regulation | In sAPPα-treated SH-SY5Y neuroblastoma cells, ISM2 mRNA was reported as up-regulated in a MAPK-related transcriptional response linked by the authors to broader APP/sAPPα neuroprotective signaling. | SH-SY5Y cells; sAPPα treatment; differential display with qPCR validation context. | Direction: up-regulated; no ISM2-specific fold-change or p-value in retrieved excerpt. | Masi M et al., *Int J Mol Sci* (2023), https://doi.org/10.3390/ijms24076639 | (pqac-00000008) |
| Pathway/regulation | In SARS-CoV-2-infected placentas, villous core stromal ISM2 expression was decreased within a broader placental dysfunction program involving hypoxia/vascular dysregulation signatures. | Spatial/whole-transcriptome placental profiling; SARS-CoV-2 placentas n=7 vs prepandemic controls n=9. | Direction: decreased; no ISM2-specific fold-change or p-value in retrieved excerpt. | Stylianou N et al., *Clinical & Translational Immunology* (2024), https://doi.org/10.1002/cti2.1488 | (pqac-00000009) |
| Disease/biomarker application | ISM2 was decreased in preeclampsia compared with normotensive pregnancy controls; placental immunohistochemistry supported reduced expression. | Prospective cross-sectional human study; serum sandwich ELISA and placental IHC; total n=81 (30 preeclampsia, 21 gestational hypertension, 30 controls). | Preeclampsia vs controls: P = 0.036. | Martinez C et al., *Heliyon* (2020), https://doi.org/10.1016/j.heliyon.2020.e05096 | (pqac-00000006) |
| Disease/biomarker application | ISM2 was reported as overexpressed in choriocarcinoma, contrasting with its decrease in preeclampsia and suggesting value as a placental trophoblast-associated disease marker. | Human placental/choriocarcinoma tissue analysis with immunohistochemistry context. | Qualitative overexpression reported; no fold-change retrieved. | Martinez C et al., *Heliyon* (2020), https://doi.org/10.1016/j.heliyon.2020.e05096 | (pqac-00000003, pqac-00000006) |
| Disease/biomarker application | ISM2 was one of 14 verified plasma biomarkers for ectopic pregnancy and showed lower abundance in ectopic pregnancy than intrauterine pregnancy/early pregnancy loss in the verification cohort. | Discovery LC-MS/MS and verification PRM-MS in plasma; discovery n=48 (16 IUP, 16 EPL, 16 EP), verification n=74 (25 IUP, 24 EPL, 25 EP). | Significant at FDR ≤ 5%; candidate biomarker AUCs in the verified set included ISM2 at 0.941. | Beer LA et al., *Clinical Proteomics* (2023), https://doi.org/10.1186/s12014-023-09425-w | (pqac-00000004, pqac-00000005, pqac-00000010) |
| Disease/biomarker application | ISM2 appeared in top-performing circulating microparticle (CMP) protein panels for placenta accreta spectrum (PAS) in both second and third trimesters, indicating reproducible inclusion in multi-protein classifiers. | Maternal plasma CMP proteomics; PAS cases n=35, controls n=70; samples at median 26 ± 2 weeks and 35 ± 2 weeks. | Top second-trimester panel mean AUC 0.83; top third-trimester panel mean AUC 0.78; observed vs permuted AUCs 0.72 vs 0.45 (p < 2.20e−16) and 0.60 vs 0.52 (p = 2.79e−5), respectively. | Yu HY et al., *Scientific Reports* (2023), https://doi.org/10.1038/s41598-022-24869-0 | (pqac-00000007) |
| Disease association overview | Curated disease-target resources list recurrent associations of human ISM2 with preeclampsia, colorectal cancer/carcinoma, neoplasm, and malunion fracture, but current evidence scores are modest and driven by limited literature. | Open Targets disease-target aggregation. | Evidence size 4 for listed diseases; scores include colorectal cancer 0.0872, neoplasm 0.0948, preeclampsia 0.0507. | Open Targets Platform query for ISM2 (accessed via tool context; current aggregation) | (pqac-00000000) |


*Table: This table compiles key functional-annotation evidence for human ISM2/Isthmin-2 from the retrieved literature and database sources. It highlights where evidence is experimental versus inferred, and captures the main quantitative biomarker results currently available.*