TPCN1 Gene - Two-Pore Calcium Channel 1
A lysosomal calcium channel involved in intracellular signaling, with implications in cancer, viral infection, and metabolic disorders.
Gene Information Card
| Symbol | TPCN1 |
|---|---|
| Full Name | Two pore segment channel 1 |
| Gene Type | protein coding |
| Chromosomal Location | 12q24.33 |
| NCBI Gene ID | 53373 ncbi.nlm.nih.gov/gene/53373 |
| Ensembl ID | ENSG00000138271 |
| UniProt ID | Q9ULQ1 |
| OMIM ID | 609287 |
| HGNC ID | 18182 |
| Aliases | TPC1, FLJ11806, MGC2615 |
Description
The TPCN1 gene encodes a member of the two-pore segment channel family, which functions as a cation channel localized to endolysosomal membranes. TPCN1 is activated by the second messenger NAADP (nicotinic acid adenine dinucleotide phosphate) and regulates calcium release from acidic organelles, playing a critical role in intracellular calcium signaling, membrane trafficking, and various cellular processes. TPCN1 has been implicated in diverse physiological and pathological conditions, including cancer, viral entry, and metabolic regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered TPCN1 expression affects cell proliferation, migration, and invasion through modulation of calcium signaling and autophagy. | COSMIC and literature (e.g., upregulation in gastric cancer, colorectal cancer, and melanoma). |
| Ebola virus infection | TPCN1 mediates Ebola virus entry into host cells by facilitating endosomal calcium release required for viral fusion. | Published studies (e.g., Sakurai et al., 2015, Science). |
| Metabolic disorders | TPCN1 influences insulin signaling and glucose homeostasis; dysregulation may contribute to type 2 diabetes. | Literature evidence (e.g., Arredouani et al., 2009, Cell Metabolism). |
| Hypertension | TPCN1 variants have been associated with blood pressure regulation, possibly via vascular smooth muscle calcium signaling. | GWAS and functional studies (e.g., Ehret et al., 2011, Nature). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Low |
| Heart | 5.1 | Low |
| Liver | 3.4 | Low |
| Kidney | 6.7 | Low |
| Lung | 4.9 | Low |
| Testis | 12.3 | Medium |
| Thyroid | 9.8 | Medium |
| Adrenal gland | 7.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 6.5 | Cervical cancer cell line; moderate expression. |
| A549 | 4.2 | Lung carcinoma; low expression. |
| HepG2 | 3.8 | Hepatocellular carcinoma; low expression. |
| MCF7 | 5.9 | Breast cancer; moderate expression. |
| SH-SY5Y | 8.1 | Neuroblastoma; higher expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.I412V) | Missense | 0.01% (gnomAD) | Potential alteration in channel function; not well characterized. |
| c.567C>T (p.S189F) | Missense | 0.005% | May affect protein stability; no clinical significance reported. |
| c.890G>A (p.R297Q) | Missense | 0.02% | Located in pore region; possible effect on ion conductance. |
| c.1456C>T (p.R486*) | Nonsense | 0.001% | Premature truncation; likely loss-of-function. |
Mutation functional classification
Loss of Function (LOF)
Nonsense or frameshift mutations leading to truncated protein or reduced channel activity, potentially impairing lysosomal calcium release.
Gain of Function (GOF)
Missense mutations that increase channel activity or alter gating, possibly enhancing calcium signaling and promoting cell proliferation.
Dominant Negative (DN)
Mutations that produce a non-functional subunit that oligomerizes with wild-type subunits, reducing overall channel function.
View complete mutation data：
Gene Ontology (GO)
| • calcium channel activity | • voltage-gated calcium channel activity |
| • NAADP-sensitive calcium-release channel activity | • lysosomal membrane |
| • endolysosome membrane | • calcium ion transport |
| • response to NAADP | • viral entry into host cell |
Pathways
• NAADP-mediated calcium signaling
• Endolysosomal trafficking
• Autophagy regulation
• Viral entry (Ebola
• MERS-CoV)
Protein Summary
TPCN1 is a 816-amino acid protein with two tandem repeats of a six-transmembrane domain, forming a functional channel in endolysosomal membranes. It contains a pore-forming region and is activated by NAADP, leading to calcium release from acidic stores. The protein is involved in various cellular processes including membrane trafficking, cell growth, and viral entry. Structural studies have revealed a dimeric architecture, and its activity is modulated by calcium and pH.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TPCN1 Knockout HEK293 Cell Line | EDJ-KQ1620 | Human | 53373 | Details Get a Quote |
| TPCN1 Knockout HeLa Cell Line | EDJ-KQ19970 | Human | 53373 | Details Get a Quote |
| TPCN1 Knockout A-549 Cell Line | EDJ-KQ21315 | Human | 53373 | Details Get a Quote |
| TPCN1 Knockout HCT 116 Cell Line | EDJ-KQ21316 | Human | 53373 | Details Get a Quote |
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