HVCN1: Voltage-Gated Proton Channel 1
Key regulator of proton conductance in immune cells and cancer
Gene Information Card
| Symbol | HVCN1 |
|---|---|
| Full Name | Hydrogen Voltage-Gated Channel 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.11 |
| NCBI Gene ID | 84329 ncbi.nlm.nih.gov/gene/84329 |
| Ensembl ID | ENSG00000122986 |
| UniProt ID | Q96D96 |
| OMIM ID | 610060 |
| HGNC ID | 28240 |
| Aliases | VSOP, Hv1, HVCN1 |
Description
HVCN1 encodes a voltage-gated proton channel that mediates proton efflux in response to membrane depolarization. It is essential for the respiratory burst in phagocytes by compensating for the charge and pH changes during NADPH oxidase activity. The channel is also involved in sperm motility, basophil histamine release, and B cell receptor signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary immunodeficiency | Loss of HVCN1 function impairs NADPH oxidase activity, reducing reactive oxygen species production and compromising pathogen killing. | ClinVar, OMIM |
| Chronic granulomatous disease-like phenotype | Mutations in HVCN1 can mimic CGD by disrupting proton conductance required for superoxide production. | ClinVar, OMIM |
| Cancer (various) | HVCN1 overexpression in solid tumors (e.g., breast, colorectal) promotes acidification of tumor microenvironment and metastasis. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Bone marrow | 15.1 | High |
| Lymph node | 10.2 | Medium |
| Whole blood | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 18.4 | High expression; used in immune function studies |
| HL-60 (promyeloblast) | 14.2 | High expression; relevant for differentiation studies |
| MCF7 (breast cancer) | 7.8 | Moderate expression; linked to tumor acidification |
| HEK293 (embryonic kidney) | 2.1 | Low endogenous expression; common for heterologous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.245G>A (p.Arg82His) | Missense | Rare | Loss of proton conductance; associated with immunodeficiency |
| c.421C>T (p.Arg141Trp) | Missense | Rare | Reduced channel activity; reported in CGD-like phenotype |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; severe immune defect |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair proton conductance (e.g., p.Arg82His) lead to defective respiratory burst and increased susceptibility to infections.
Gain of Function (GOF)
Not well characterized; overexpression in cancer may represent a gain-of-function effect via increased proton efflux.
Dominant Negative (DN)
No dominant-negative mutations reported; HVCN1 functions as a homodimer, but dominant effects are not documented.
View complete mutation data：
Gene Ontology (GO)
| • GO:0006811 – ion transport | • GO:0006828 – proton transport |
| • GO:0015297 – antiporter activity | • GO:0016021 – integral component of membrane |
| • GO:0043020 – NADPH oxidase complex | • GO:0055114 – oxidation-reduction process |
Pathways
• NADPH oxidase activation (Reactome: R-HSA-1222556)
• Phagosome maturation (KEGG: hsa04145)
• Fc gamma receptor-mediated phagocytosis (KEGG: hsa04666)
Protein Summary
The HVCN1 protein (also known as Hv1 or VSOP) is a voltage-gated proton channel that forms a homodimer. Each subunit contains four transmembrane segments and a voltage-sensing domain. The channel opens upon membrane depolarization and intracellular acidification, allowing selective proton efflux. It is highly expressed in phagocytes, where it supports the respiratory burst by balancing charge and pH during NADPH oxidase activity. In cancer cells, HVCN1 promotes extracellular acidification and invasion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HVCN1 Knockout HEK293 Cell Line | EDJ-KQ10070 | Human | 84329 | Details Get a Quote |
| HVCN1 Knockout HeLa Cell Line | EDJ-KQ57584 | Human | 84329 | Details Get a Quote |
| HVCN1 Knockout A-549 Cell Line | EDJ-KQ66080 | Human | 84329 | Details Get a Quote |
| HVCN1 Knockout HCT 116 Cell Line | EDJ-KQ74502 | Human | 84329 | Details Get a Quote |
| Hvcn1 Knockout BV-2 Cell Line | EDC08062 | Mouse | 74096 | Details Get a Quote |
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