PACC1: Proton-Activated Chloride Channel 1
A key regulator of cellular chloride conductance in response to acidic pH
Gene Information Card
| Symbol | PACC1 |
|---|---|
| Full Name | Proton-Activated Chloride Channel 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 55248 ncbi.nlm.nih.gov/gene/55248 |
| Ensembl ID | ENSG00000117569 |
| UniProt ID | Q8N6M3 |
| OMIM ID | 617949 |
| HGNC ID | 26270 |
| Aliases | TMEM206, PAC, C1orf85 |
Description
PACC1 (Proton-Activated Chloride Channel 1), also known as TMEM206, encodes a transmembrane protein that forms a proton-activated chloride channel. This channel is activated by extracellular acidification and mediates chloride ion conductance, playing a role in cellular responses to acidic pH, including cell volume regulation and acid-induced cell death. The gene is widely expressed and has been implicated in cancer and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered expression may modulate acid-induced apoptosis and tumor microenvironment pH regulation | NCBI Gene, COSMIC |
| Neurodevelopmental disorders | Potential role in neuronal chloride homeostasis; mutations reported in ClinVar | ClinVar |
| Epilepsy | Dysregulated chloride conductance may contribute to neuronal hyperexcitability | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.2 | Low |
| Liver | 6.1 | Low |
| Kidney | 15.3 | Medium |
| Testis | 20.1 | High |
| Colon | 10.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.5 | High expression |
| HeLa | 12.3 | Medium expression |
| SH-SY5Y | 14.7 | Medium-high expression |
| A549 | 9.8 | Low-medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | 0.01% | Unknown functional effect |
| c.452G>A (p.Arg151His) | Missense | 0.005% | Reported in ClinVar as uncertain significance |
| c.788delC | Frameshift | <0.001% | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., c.788delC) are predicted to truncate the protein, abolishing channel activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not established; potential for missense variants to interfere with channel assembly.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated chloride channel activity (GO:0005247) | • plasma membrane (GO:0005886) |
| • chloride transport (GO:0006821) | • integral component of membrane (GO:0016021) |
| • transmembrane transport (GO:0055085) |
Pathways
• Acid-sensing ion channels
• Chloride channel-mediated ion transport
Protein Summary
PACC1 encodes a 286-amino acid transmembrane protein with four predicted transmembrane domains. It assembles as a homodimer to form a proton-activated chloride channel. The channel is activated by extracellular pH below 6.0, conducting chloride ions with moderate selectivity. It is involved in cellular responses to acidosis, including regulatory volume decrease and apoptosis. The protein is localized to the plasma membrane and is expressed in multiple tissues, with highest levels in testis and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PACC1 Knockout HEK293 Cell Line | EDJ-KQ145 | Human | 55248 | Details Get a Quote |
| PACC1 Knockout HeLa Cell Line | EDJ-KQ43727 | Human | 55248 | Details Get a Quote |
| PACC1 Knockout A-549 Cell Line | EDJ-KQ44947 | Human | 55248 | Details Get a Quote |
| PACC1 Knockout HCT 116 Cell Line | EDJ-KQ44948 | Human | 55248 | Details Get a Quote |
