Protein / target
Non-selective voltage-gated ion channel VDAC1
Protein at a glance
Biological role
Voltage-gated monoatomic anion channel
Strongest disease association
Alcohol drinking
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane.
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Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:30061676, PubMed:8420959). The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis (PubMed:10661876, PubMed:11845315, PubMed:18755977, PubMed:8420959). It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (PubMed:10661876, PubMed:18755977, PubMed:8420959). The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:18755977, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterols cholesterol and oxysterol (PubMed:18755977, PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756). May mediate ATP export from cells (PubMed:30061676). Part of a complex composed of HSPA9, ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent apoptosis by facilitating calcium transport from the ER lumen to the mitochondria intermembrane space thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity). Mediates cytochrome c efflux (PubMed:20230784)
Subcellular location
Domains and Gene Ontology detail (35)Hide
Gene Ontology
- Cextracellular exosome
- Cmembrane
- Cmembrane raft
- Cmitochondrial membrane
- Cmitochondrial nucleoid
- Cmitochondrial outer membrane
- Cmitochondrial permeability transition pore complex
- Cmitochondrion
- Cnucleus
- Cplasma membrane
- Cpore complex
- FATP binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Lipid & lipoprotein metabolism
- ·Non-selective voltage-gated ion channel that mediates the transport of anions and cation…
- ·cholesterol binding
- ·oxysterol binding
- ·lipid transport
Ion channel gating
- ·voltage-gated monoatomic anion channel activity
- ·voltage-gated monoatomic ion channel activity
Ligand-gated signalling
- ·Non-selective voltage-gated ion channel that mediates the transport of anions and cation…
Apoptosis & cell death
- ·apoptotic process
- ·negative regulation of apoptotic process
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene VDAC1
Gene-level evidence surfaced through the gene VDAC1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Tractability
Small molecules — Emerging
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (8)Hide
Raw Open Targets tractability assessment buckets, by modality.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.