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Protein / target

Non-selective voltage-gated ion channel VDAC1

Encoded byVDAC1P21796Homo sapiensSwiss-Prot
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Voltage-gated monoatomic anion channel

Strongest disease association

Alcohol drinking

Via encoding gene VDAC1 · Genetic evidence · score 0.42

Research activity

Emerging research

1 papers · latest 2020

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

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.

View complete UniProt function annotation

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

Mitochondrion outer membraneCell membraneMembrane raft
Domains and Gene Ontology detail (35)

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

283 aa · 31 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GOIon channel gatingGOLigand-gated signallingUniProtApoptosis & cell deathGO
View supporting evidence

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

Open Targets 26

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.

Alcohol drinking
0.42Limited support

Genetic evidence dominant · Open Targets 0.25

Dislocation
0.39Limited support

Genetic evidence dominant · Open Targets 0.24

Urolithiasis
0.37Limited support

Genetic evidence dominant · Open Targets 0.23

Glaucoma, Open-Angle
0.36Limited support

Genetic evidence dominant · Open Targets 0.22

Neurodegenerative Diseases
0.35Preliminary

Pathway evidence dominant · Open Targets 0.51 · no direct causal or clinical evidence

View evidence synthesis (5)
Alcohol drinkingLimited support
0.42
agreement 0.300.54
Genetic100%

Open Targets aggregate 0.25 · 1 independent evidence family

DislocationLimited support
0.39
agreement 0.270.51
Genetic100%

Open Targets aggregate 0.24 · 1 independent evidence family

UrolithiasisLimited support
0.37
agreement 0.250.49
Genetic100%

Open Targets aggregate 0.23 · 1 independent evidence family

Glaucoma, Open-AngleLimited support
0.36
agreement 0.240.48
Genetic100%

Open Targets aggregate 0.22 · 1 independent evidence family

Neurodegenerative DiseasesPreliminary
0.35
agreement 0.170.52
Pathway95%Literature5%

Open Targets aggregate 0.51 · 2 independent evidence families · no direct causal or clinical evidence

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.

Show all associations
Neurodegenerative Diseases0.51
Autoimmune disorder of central nervous system0.33
Alcohol drinking0.25
Dislocation0.24
Urolithiasis0.23
Glaucoma, Open-Angle0.22
Cartilage Diseases0.21
Neoplasms0.12
Breast Neoplasms0.11

Tractability

Small moleculesEmerging

Feasibility evidence (structure with ligand and med-quality pocket) — no clinical-stage drug of this modality recorded.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Structure with LigandSM · Med-Quality PocketAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life Data

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2020

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Shoshan-Barmatz V · Biomolecules · 2020

Recent

Europe PMC papers linked directly to this protein.