VDAC3

protein-coding

voltage dependent anion channel 3, the group of Voltage dependent anion channels

Gene summary

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]

MANE transcript

NM_005662.7

Inheritance

—

ClinVar variants

U:37

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr8:42,391,624-42,405,937

External References & Databases

Ensembl (ENSG00000078668)

Transcript & Mutation Effects

hg38 • Region Span ~14.3 kb

Loading mutation effect viewer...

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 VDAC3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 31

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005662.7. 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			1 clinvar			1
missense			34 clinvar			34
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	37	0	0	37

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005662.7	RefSeq	NP_005653.3	8	MANE Select
ENST00000022615.9	Ensembl	ENSP00000022615.4	8	MANE Select
NM_001135694.3	RefSeq	NP_001129166.1	9	Standard
NM_001413552.1	RefSeq	NP_001400481.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Huntington,s disease - Homo sapiens (human)
HTLV-I infection - Homo sapiens (human)
Necroptosis - Homo sapiens (human)
Calcium signaling pathway - Homo sapiens (human)
NOD-like receptor signaling pathway - Homo sapiens (human)

Biological Process

behavioral fear response
neuron-neuron synaptic transmission
learning
inorganic anion transport
adenine transport

Molecular Function

nucleotide binding
voltage-gated anion channel activity
porin activity

Cellular Component

nucleus
mitochondrion
mitochondrial outer membrane
pore complex
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000521158
Coding exons: 9
Length: 14274
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125744
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	113	151	0.749	0.00000739	1860
Missense (PolyPhen)		23	44.778	0.51365		629
Synonymous	1.89	39	57.2	0.682	0.00000302	536
Loss of Function	3.64	0	15.5	0.00	7.15e-7	202

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)	0.000026	0.000026	rare
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 that allows diffusion of small hydrophilic molecules. {ECO:0000250}.;

Recessive Scores

pRec: 0.0897

Intolerance Scores

RVIS EVS: 0.22
RVIS percentile EVS: 67.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.942

Gene Damage Prediction

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