VDAC3

Chr 8

voltage dependent anion channel 3

Also known as: HD-VDAC3, VDAC-3

NCBI Gene: 7419 ENSG00000078668 UniProt: Q9Y277 OMIM: 610029

This gene encodes a voltage-dependent anion channel (VDAC), and belongs to the mitochondrial porin family. VDACs are small, integral membrane proteins that traverse the outer mitochondrial membrane and conduct ATP and other small metabolites. They are known to bind several kinases of intermediary metabolism, thought to be involved in translocation of adenine nucleotides, and are hypothesized to form part of the mitochondrial permeability transition pore, which results in the release of cytochrome c at the onset of apoptotic cell death. Alternatively transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.995

Z-score 3.64

OE 0.00 (0.00–0.19)

Highly constrained

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

Missense Constraint?

1.10Z-score

OE missense 0.75 (0.64–0.88)

113 obs / 150.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.19)

0≤0.351.4

Missense OE?0.75 (0.64–0.88)

0≤0.61.4

Synonymous OE?0.68

0≤1.21.6

LoF obs/exp: 0 / 15.5Missense obs/exp: 113 / 150.9Syn Z: 1.89

Background carrier burden — how many people carry a rare variant somewhere in VDAC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

288 rare PASS variants

Rare truncating (LoF)

1 in 9,000

30 rare PASS variants

Rare synonymous (reference)

1 in 370

105 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for VDAC3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 370	1 in 8,500
South Asian	~43k	1 in 310	1 in 2,400
Remaining (unassigned)	~30k	1 in 270	≈ 1 in 15,000
European (Finnish)	~27k	1 in 570	≈ 1 in 27,000
Admixed American	~22k	1 in 240	≈ 1 in 11,000
African / African American	~21k	1 in 310	≈ 1 in 9,300
East Asian	~20k	1 in 270	1 in 4,000
Ashkenazi Jewish	~13k	1 in 380	none seen
Middle Eastern	~2,884	1 in 460	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.