VDAC1

Chr 5

voltage dependent anion channel 1

Also known as: PORIN, VDAC-1

NCBI Gene: 7416ENSG00000213585UniProt: P21796

This gene encodes a voltage-dependent anion channel protein that is a major component of the outer mitochondrial membrane. The encoded protein facilitates the exchange of metabolites and ions across the outer mitochondrial membrane and may regulate mitochondrial functions. This protein also forms channels in the plasma membrane and may be involved in transmembrane electron transport. Alternate splicing results in multiple transcript variants. Multiple pseudogenes of this gene are found on chromosomes 1, 2 3, 6, 9, 12, X and Y.[provided by RefSeq, Sep 2010]

43
ClinVar variants
16
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— VDAC1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 26 VUS of 43 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.31LOEUF
pLI 0.973
Z-score 3.41
OE 0.06 (0.02–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.33Z-score
OE missense 0.71 (0.61–0.82)
114 obs / 161.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.61–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 1 / 15.5Missense obs/exp: 114 / 161.4Syn Z: 0.44

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS26
Likely Benign1
15
Pathogenic
1
Likely Pathogenic
26
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
24
2
0
26
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02419043

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

VDAC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — VDAC1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GRP75-faciliated Mitochondria-associated ER Membrane (MAM) Integrity controls Cisplatin-resistance in Ovarian Cancer Patients.
Li J et al.·Int J Biol Sci
2022Cohort
Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension.
Zhou X et al.·Circ Res
2023
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1.
Geisler S et al.·Nat Cell Biol
2010
mtDNA release promotes cGAS-STING activation and accelerated aging of postmitotic muscle cells.
Li Y et al.·Cell Death Dis
2024
Selective BCL-2 inhibitor triggers STING-dependent antitumor immunity via inducing mtDNA release.
Zhang W et al.·J Immunother Cancer
2025
Cholesterol induction in CD8(+) T cell exhaustion in colorectal cancer via the regulation of endoplasmic reticulum-mitochondria contact sites.
Shuwen H et al.·Cancer Immunol Immunother
2023
Oxidative stress regulates the catalytic activity and mitochondrial localization of HK2 in trophoblast by regulating K346 lactylation.
Chen Z et al.·FASEB J
2025
A novel glycolysis-related gene signature for predicting prognosis and immunotherapy efficacy in breast cancer.
Huang R et al.·Front Immunol
2025
STING regulates aging-related osteoporosis by mediating the Hk2-Vdac1 mitochondrial axis.
Cai W et al.·Free Radic Biol Med
2024
The Wolfram-like variant WFS1(E864K) destabilizes MAM and compromises autophagy and mitophagy in human and mice.
Patergnani S et al.·Autophagy
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools