VDAC1

protein-coding

voltage dependent anion channel 1, the group of Voltage dependent anion channels

Gene summary

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]

MANE transcript

NM_003374.3

Inheritance

—

ClinVar variants

U:30

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr5:133,971,871-134,004,975

External References & Databases

Ensembl (ENSG00000213585)

Transcript & Mutation Effects

hg38 • Region Span ~33.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VDAC1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 24

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003374.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			25 clinvar			25
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	30	0	0	30

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 125 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003374.3	RefSeq	NP_003365.1	8	MANE Select
ENST00000265333.8	Ensembl	ENSP00000265333.3	8	MANE Select
NM_001401008.1	RefSeq	NP_001387937.1	8	Standard
NM_001401009.1	RefSeq	NP_001387938.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Benzodiazepine Pathway, Pharmacodynamics
Influenza A - Homo sapiens (human)
Huntington,s disease - Homo sapiens (human)
HTLV-I infection - Homo sapiens (human)
Necroptosis - Homo sapiens (human)

Biological Process

pyruvate metabolic process
anion transport
apoptotic process
inorganic anion transport
viral process

Molecular Function

protein binding
voltage-gated anion channel activity
porin activity
protein kinase binding
identical protein binding

Cellular Component

nucleus
mitochondrion
mitochondrial outer membrane
mitochondrial permeability transition pore complex
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265333
Coding exons: 8
Length: 33219
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125733
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.33	114	161	0.706	0.00000920	1827
Missense (PolyPhen)		27	33.432	0.80761		497
Synonymous	0.443	63	67.6	0.931	0.00000449	559
Loss of Function	3.41	1	15.5	0.0645	7.41e-7	187

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Forms a channel through the mitochondrial outer membrane and also the plasma membrane. 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. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:11845315, PubMed:18755977, PubMed:20230784, PubMed:8420959). 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). {ECO:0000269|PubMed:11845315, ECO:0000269|PubMed:15033708, ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:25296756, ECO:0000269|PubMed:8420959}.;

Intolerance Scores

RVIS EVS: -0.3
RVIS percentile EVS: 32.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.643

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium