| Topic/Claim | Evidence summary (1-2 sentences, include quantitative stats where available) | Study type/model | Publication (authors, journal) | Pub date (Month Year) | URL/DOI |
|---|---|---|---|---|---|
| NENF identity and heme-dependent neurotrophic function | Neudesin/NENF was established as a **secreted extracellular heme-binding protein** whose neurotrophic activity depends on its **cytochrome b5-like heme/steroid-binding domain**. Biochemical assays used recombinant neudesin with hemin/protoporphyrin IX, and cell-based assays were reported as mean ± S.E. from **4 independent experiments**; treatment conditions included **10 ng/mL** neudesin/neudesin-hemin and **100 nM** hemin in functional assays (pqac-00000014). | Primary mechanistic biochemistry and cell biology; recombinant protein; neuronal assays | Kimura et al., *Journal of Biological Chemistry* | Feb 2008 | https://doi.org/10.1074/jbc.m706679200 |
| Current understanding in CNS: secretion, MAPR family, MAPK/PI3K signaling | Review summarizes neudesin as a **secreted neurotrophic factor** abundantly expressed in the CNS, a **MAPR-family** protein with a cytochrome b5-like heme/steroid-binding domain, and notes that heme binding is essential for in vitro activity. Neudesin activates **MAPK/ERK** and **PI3K/AKT** signaling and has anorexigenic hypothalamic effects; no receptor had been definitively identified (pqac-00000011, pqac-00000012). | Authoritative review of primary CNS/neurobiology literature | Kimura et al., *Frontiers in Neuroscience* | May 2013 | https://doi.org/10.3389/fnins.2013.00111 |
| Neudesin restrains energy expenditure; KO protects against diet-induced obesity | Neudesin-KO mice were reported to be **resistant to high-fat-diet-induced obesity and metabolic dysfunction**, with increased **sympathetic activity**, **heat production**, **fatty-acid oxidation in BAT**, and **lipolysis in WAT**. Body weights were similar to WT at **E18.5 and 8 weeks** but diverged by **16 weeks** under the study conditions (pqac-00000015). | In vivo mouse knockout physiology/metabolism study | Ohta et al., *Scientific Reports* | May 2015 | https://doi.org/10.1038/srep10049 |
| Integrated functional model: neural, metabolic, and tumor roles | Review synthesizes evidence that NENF is a **172-aa secreted MAPR protein** with key heme-binding tyrosines and likely signals via **MAPK/ERK**, **PI3K/AKT**, and in some contexts **GPCR-linked** pathways (PTX sensitivity or cAMP/PKA signaling). It also summarizes KO anxiety phenotypes, hypothalamic food-intake suppression, HFD-obesity resistance, adipogenesis regulation, and tumorigenic actions (pqac-00000008, pqac-00000009, pqac-00000010). | Authoritative review integrating structural, signaling, and physiology studies | Ohta et al., *Frontiers in Molecular Biosciences* | May 2015 | https://doi.org/10.3389/fmolb.2015.00024 |
| GIG47/NENF as oncogenic secreted MAPR protein with structural pocket | GIG47 (NENF/neudesin) was overexpressed in multiple human tumors, promoted **MCF7 invasiveness** and **in vivo tumorigenicity**, and its effects were linked to **MAPK** and **PI3K** pathways. Structural work defined a fold with **4 α-helices and 6 β-strands** and identified a potential **heme/steroid-binding pocket** between helices α2 and α3 (pqac-00000010). | Primary cancer biology plus structural/NMR study | Han et al., *BMC Cancer* | Jul 2012 | https://doi.org/10.1186/1471-2407-12-274 |
| Circulating neudesin changes with fasting and bariatric/endoscopic weight-loss interventions | Human serum neudesin was measured in obesity/T2DM intervention cohorts: **15** obese T2DM patients with DJBL, **17** obese patients undergoing gastric plication, **15** subjects in **72-hour fasting**, and **12** healthy controls. DJBL increased serum neudesin from **1.77 ± 0.86** to **2.28 ± 1.27** and **2.13 ± 1.02 ng/mL** (**P=0.001**), while fasting decreased it from **1.74 ± 0.54** to **1.46 ± 0.48 ng/mL** (**P=0.001**) (pqac-00000013). | Human clinical biomarker/intervention study | Kratochvilova et al., *Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy* | Mar 2019 | https://doi.org/10.2147/DMSO.S193259 |
| NENF is a dysregulated immune/metabolic gene in aplastic anemia | Single-cell RNA-seq of peripheral blood from **5 children with aplastic anemia** and **3 healthy donors** identified **NENF** among key differentially expressed genes and showed it was **significantly higher** in AA. Metabolic pathway analysis found **lysine degradation** enrichment in AA (**q = 0.0051**), with T-cell abnormalities centered on glycolysis/gluconeogenesis and NK-cell abnormalities on oxidative phosphorylation (pqac-00000016, pqac-00000018). | 2023 scRNA-seq immune-disease study | Zhou et al., *Frontiers in Oncology* | Mar 2023 | https://doi.org/10.3389/fonc.2023.1075408 |
| Serum neudesin is decreased in PCOS and varies by adiposity/age | In **90 women** (**60 PCOS**, **30 controls**), serum neudesin was significantly lower in PCOS (**0.75 ± 0.05 ng/mL**) than controls (**2.86 ± 0.06 ng/mL**, **P<0.05**). Within PCOS, values were lower in younger, obese, and high waist/hip-ratio groups: e.g., obese **0.43 ± 0.04** vs overweight **1.2 ± 0.03 ng/mL**; high WHR **0.5 ± 0.04** vs moderate WHR **1.25 ± 0.03 ng/mL**; no significant difference by infertility subtype (pqac-00000022, pqac-00000025). | 2024 human serum biomarker study; ELISA | Salih & Al-Dujaili, *BIO Web of Conferences* | Jan 2024 | https://doi.org/10.1051/bioconf/202410804012 |
| NENF is amplified/overexpressed in TNBC and promotes EMT-linked metastasis | A 2024 TNBC single-cell/integrative study identified NENF as a metastasis-related gene; in TCGA-TNBC it showed amplification in **88/114 cases (77.2%)**. Validation included **30 paired TNBC/adjacent samples** by RT-qPCR and **20 paired samples** by IHC; NENF knockdown reduced invasion/migration, and depletion increased **E-cadherin** while decreasing **N-cadherin/Vimentin**, supporting an EMT-promoting role (pqac-00000003, pqac-00000004, pqac-00000019). | 2024 single-cell transcriptomics + bulk cohorts + tissue/cell-line validation | Wang et al., *Cancer Cell International* | Sep 2024 | https://doi.org/10.1186/s12935-024-03505-z |
| Translational evidence line from Open Targets | Open Targets lists NENF associations with **obesity**, **brain neoplasm**, **triple-negative breast cancer**, **ovarian dysfunction**, and **skeletal abnormalities**. The platform captures literature-backed evidence including TNBC and obesity studies, and the returned disease-association scores in the current query included **0.0743** for TNBC, **0.0611** for obesity, and **0.0819** for ovarian dysfunction (pqac-00000000, pqac-00000005). | Integrated target–disease evidence platform / knowledgebase | Open Targets Platform (Buniello et al., platform citation) | 2025 | https://platform.opentargets.org/target/ENSG00000117691 |


*Table: This table summarizes core functional-annotation evidence for human NENF/neudesin (UniProt Q9UMX5), combining foundational mechanistic papers with recent 2023-2024 disease and biomarker studies. It highlights localization, heme dependence, signaling, physiological roles, and translational associations with quantitative details where available.*