TPCN2: Two-Pore Channel 2
A lysosomal ion channel regulating calcium and sodium signaling, linked to pigmentation and viral entry.
Gene Information Card
| Symbol | TPCN2 |
|---|---|
| Full Name | Two-Pore Segment Channel 2 |
| Gene Type | Protein-coding |
| Chromosomal Location | 11q13.3 |
| NCBI Gene ID | 219931 ncbi.nlm.nih.gov/gene/219931 |
| Ensembl ID | ENSG00000162367 |
| UniProt ID | Q8NHX9 |
| OMIM ID | 612163 |
| HGNC ID | 20819 |
| Aliases | TPC2, TPCN2, FLJ38679 |
Description
TPCN2 encodes two-pore channel 2 (TPC2), a lysosomal ion channel that mediates calcium and sodium release from acidic organelles in response to nicotinic acid adenine dinucleotide phosphate (NAADP). TPC2 regulates endolysosomal trafficking, autophagy, and melanosome biogenesis. Variants in TPCN2 are associated with pigmentation traits and hair color. The channel also serves as a host factor for entry of Ebola virus and SARS-CoV-2.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pigmentation variation (hair color) | TPCN2 variants alter melanosome pH and calcium signaling, affecting melanin synthesis | GWAS and candidate gene studies (OMIM 612163) |
| Ebola virus disease | TPC2 is required for Ebola virus entry via endosomal fusion | Cell-based infection assays (PMID: 21878987) |
| COVID-19 (SARS-CoV-2) | TPC2 facilitates viral entry through endolysosomal pathway | In vitro studies (PMID: 33243852) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 15.2 | Medium |
| Lung | 8.7 | Low |
| Spleen | 6.3 | Low |
| Testis | 5.1 | Low |
| Brain | 3.4 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung) | 12.5 | High expression |
| HEK293 (embryonic kidney) | 9.8 | Moderate |
| HepG2 (liver) | 4.2 | Low |
| K562 (leukemia) | 2.1 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3829241 (G734E) | Missense | 0.28 (global) | Alters channel conductance; associated with blond hair |
| rs1015451 (M484L) | Missense | 0.15 (European) | Reduced NAADP sensitivity; linked to brown hair |
| rs1551305 (P369L) | Missense | 0.05 (East Asian) | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
G734E reduces calcium release activity; M484L decreases NAADP sensitivity.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NAADP-mediated calcium signaling (Reactome: R-HSA-4086398)
• Endolysosomal transport (Reactome: R-HSA-432722)
• Ebola virus entry (KEGG: hsa05164)
Protein Summary
TPC2 is a 752-amino acid lysosomal membrane protein with two tandem pore-forming domains. It forms a homodimer or heterodimer with TPC1. The channel is activated by NAADP and inhibited by ATP and mTOR. TPC2 regulates luminal pH and calcium release, influencing endosomal trafficking, autophagy, and melanogenesis. Structural studies reveal a voltage-sensing domain and a selectivity filter for calcium and sodium.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TPCN2 Knockout HEK293 Cell Line | EDJ-KQ1621 | Human | 219931 | Details Get a Quote |
| TPCN2 Knockout A-549 Cell Line | EDJ-KQ21318 | Human | 219931 | Details Get a Quote |
| TPCN2 Knockout HCT 116 Cell Line | EDJ-KQ21319 | Human | 219931 | Details Get a Quote |
| TPCN2 Knockout HeLa Cell Line | EDJ-KQ21320 | Human | 219931 | Details Get a Quote |
| TPCN2 Knockout Jurkat Cell Line | EDJ-KZ59 | Human | 219931 | Details Get a Quote |
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