Transfected Stable Cell Lines
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| Cat.No. | Product Name | Price |
|---|---|---|
| CSC-DC016193 | Panoply™ Human TMEM219 Knockdown Stable Cell Line | Inquiry |
| CSC-SC016193 | Panoply™ Human TMEM219 Over-expressing Stable Cell Line | Inquiry |
| Cat.No. | Product Name | Price |
|---|---|---|
| AD16520Z | Human TMEM219 adenoviral particles | Inquiry |
| LV28111L | human TMEM219 (NM_194280) lentivirus particles | Inquiry |
| Cat.No. | Product Name | Price |
|---|---|---|
| SHH430196 | shRNA set against Human TMEM219 (NM_001083613.1) | Inquiry |
| SHH430200 | shRNA set against Mouse TMEM219 (NM_026827.1) | Inquiry |
| Cat.No. | Product Name | Price |
|---|---|---|
| CDFH019852 | Human TMEM219 cDNA Clone(NM_001083613.1) | Inquiry |
| MiUTR1H-05725 | TMEM219 miRNA 3'UTR clone | Inquiry |
| MiUTR1M-00061 | TMEM219 miRNA 3'UTR clone | Inquiry |
| MiUTR1M-00062 | TMEM219 miRNA 3'UTR clone | Inquiry |
| MiUTR3H-15339 | TMEM219 miRNA 3'UTR clone | Inquiry |
| CDCB192075 | Rabbit TMEM219 ORF clone (XM_008257936.1) | Inquiry |
| CDCR261422 | Mouse Tmem219 ORF Clone(NM_028389.1) | Inquiry |
| CDCR346111 | Human TMEM219 ORF Clone(NM_001083613.1) | Inquiry |
The TMEM219 gene is located on human chromosome 9q31.3, consisting of six exons and encoding a transmembrane protein of 240 amino acids with an approximate molecular weight of 26 kDa. Two transcript variants have been identified, differing only in the 5′ untranslated region while encoding the same protein. The gene shows high expression in the lung, kidney, placenta, and small intestine. Its promoter contains a p53-binding site, suggesting regulation under DNA damage stress. Structurally, TMEM219 is a member of the tumor necrosis factor receptor (TNFR) superfamily, with an extracellular IgV-like domain, a single transmembrane region, and an intracellular death domain (DD).
The principal function of TMEM219 is to act as a specific receptor for insulin-like growth factor-binding protein 3 (IGFBP-3), initiating a caspase-dependent apoptotic pathway:
Ligand Binding and Activation: Binding of IGFBP-3 to the extracellular domain of TMEM219 promotes receptor trimerization, recruitment of the adaptor protein FADD, and subsequent activation of caspase-8. Activated caspase-8 triggers a cascade leading to effector caspase-3/7 activation and apoptosis.
Crosstalk with IGF Signaling: IGFBP-3 can suppress IGF-1 survival signaling by sequestration, while TMEM219 provides an IGF-independent mechanism for apoptosis. Together, this dual role of the IGFBP-3/TMEM219 axis positions it as a key regulator of cell fate.
TMEM219 also modulates autophagy. Under nutrient deprivation, it inhibits autophagic flux via mTORC1 signaling, potentially through AMPK phosphorylation. In pancreatic β-cell homeostasis, TMEM219 deficiency increases autophagy and β-cell mass, highlighting its role in metabolic regulation.
Figure 1. Multiple downstream pathways regulated by IGFBP-3. (Naseri N, et al., 2025)
TMEM219 exerts dual effects in type 2 diabetes:
In the liver, hyperglycemia upregulates TMEM219 expression, enhancing caspase-3 activity and hepatocyte apoptosis, thereby aggravating insulin resistance.
In adipose tissue, TMEM219 mediates IGFBP-3–induced apoptosis of preadipocytes, limiting adipose expansion and contributing to lipotoxicity.
Elevated circulating IGFBP-3 levels in diabetes have been associated with microvascular complications, suggesting TMEM219 as a potential mediator.
TMEM219 shows context-dependent roles in cancer:
Pro-tumor effects: In glioblastoma, TMEM219 promotes PD-L1 expression through STAT3 signaling, facilitating immune evasion. In breast cancer, its expression correlates with paclitaxel resistance.
Anti-tumor effects: In colorectal cancer, TMEM219 overexpression enhances 5-fluorouracil–induced apoptosis, whereas promoter methylation–mediated silencing contributes to chemoresistance.
These contrasting functions may depend on IGFBP-3 bioavailability and the repertoire of downstream adaptor proteins within the tumor microenvironment.
Genome-wide association studies have linked TMEM219 to Hermansky-Pudlak syndrome (HPS), characterized by platelet dysfunction and pulmonary fibrosis. Impaired TMEM219-mediated clearance of apoptotic alveolar type II cells may contribute to collagen accumulation. In autism spectrum disorder (ASD), TMEM219 lies within a susceptibility region on 9q31, and missense variants such as p.R112Q may affect synaptic pruning, though the mechanisms remain unresolved.
Two major challenges complicate TMEM219 research:
From a therapeutic perspective, strategies are emerging:
TMEM219 is a multifunctional receptor that integrates apoptosis, autophagy, and metabolic regulation through its interaction with IGFBP-3. Its roles in diabetes, cancer, genetic syndromes, and potentially neurological disorders underscore its biological importance. Despite challenges in dissecting its signaling complexity, TMEM219 represents a promising therapeutic target with translational applications in metabolic disease and oncology.
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