VDAC3

Summary

VDAC3 (voltage dependent anion channel 3, HGNC:12674) is a protein-coding gene on chromosome 8p11.21, encoding Non-selective voltage-gated ion channel VDAC3 (Q9Y277). Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane.

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.

Source: NCBI Gene 7419 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• Druggable target: yes
• MANE Select transcript: NM_005662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12674
Approved symbol	VDAC3
Name	voltage dependent anion channel 3
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Aliases	HD-VDAC3
Ensembl gene	ENSG00000078668
Ensembl biotype	protein_coding
OMIM	610029
Entrez	7419

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 24 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000022615, ENST00000518495, ENST00000518563, ENST00000519072, ENST00000520115, ENST00000521158, ENST00000521348, ENST00000522010, ENST00000522069, ENST00000522178, ENST00000522572, ENST00000524291, ENST00000885470, ENST00000885471, ENST00000885472, ENST00000885473, ENST00000885474, ENST00000885475, ENST00000885476, ENST00000885477, ENST00000885478, ENST00000885479, ENST00000919927, ENST00000919928, ENST00000919929, ENST00000919930, ENST00000919931, ENST00000919932, ENST00000966736, ENST00000966737

RefSeq mRNA: 12 — MANE Select: NM_005662 NM_001135694, NM_001413552, NM_001413553, NM_001413554, NM_001413555, NM_001413556, NM_001413557, NM_001413558, NM_001413559, NM_001413560, NM_001413561, NM_005662

CCDS: CCDS47850, CCDS6131

Canonical transcript exons

ENST00000022615 — 10 exons

Exon	Start	End
ENSE00001192630	42393845	42393884
ENSE00001319876	42405371	42405937
ENSE00003273621	42403311	42403461
ENSE00003479481	42394210	42394278
ENSE00003481283	42399651	42399703
ENSE00003487661	42395084	42395133
ENSE00003537626	42404867	42404924
ENSE00003569352	42398712	42398864
ENSE00003607371	42401788	42402015
ENSE00003849640	42391880	42391928

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.4442 / max 2415.4177, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88687	76.7178	1823
88688	2.6596	1182
88686	0.0667	28

Top tissues by expression

303 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.86	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.86	gold quality
endothelial cell	CL:0000115	99.85	gold quality
pancreatic ductal cell	CL:0002079	99.78	gold quality
epithelium of nasopharynx	UBERON:0001951	99.74	gold quality
male germ cell	CL:0000015	99.73	gold quality
nasopharynx	UBERON:0001728	99.73	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.70	gold quality
body of tongue	UBERON:0011876	99.66	gold quality
vastus lateralis	UBERON:0001379	99.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.65	gold quality
substantia nigra pars compacta	UBERON:0001965	99.63	gold quality
cervix squamous epithelium	UBERON:0006922	99.61	gold quality
quadriceps femoris	UBERON:0001377	99.60	gold quality
germinal epithelium of ovary	UBERON:0001304	99.58	gold quality
biceps brachii	UBERON:0001507	99.58	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.58	gold quality
esophagus squamous epithelium	UBERON:0006920	99.58	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.55	gold quality
squamous epithelium	UBERON:0006914	99.55	gold quality
gingival epithelium	UBERON:0001949	99.54	gold quality
pons	UBERON:0000988	99.53	gold quality
superior vestibular nucleus	UBERON:0007227	99.53	gold quality
choroid plexus epithelium	UBERON:0003911	99.51	gold quality
middle temporal gyrus	UBERON:0002771	99.49	gold quality
tongue	UBERON:0001723	99.45	gold quality
skeletal muscle tissue	UBERON:0001134	99.42	gold quality
heart right ventricle	UBERON:0002080	99.41	gold quality
dorsal root ganglion	UBERON:0000044	99.40	gold quality
deltoid	UBERON:0001476	99.39	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	138.72
E-MTAB-7303	no	1326.37
E-HCAD-5	no	2.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting VDAC3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-7849-3P	99.47	68.17	1224

Literature-anchored findings (GeneRIF, showing 20)

• VDAC2 and VDAC3 might have an alternative structural organization and different functions in outer dense fibers than in mitochondria (PMID:14739283)
• VDAC3 is a novel target for protein S-nigrosylation in spermatozoa. (PMID:17683036)
• VDAC3 has a limited ability to support mitochondrial respiration and has no influence in the control of ROS production. (PMID:20138821)
• The substitution of the VDAC3 N-terminus with the VDAC1 N-terminus caused the chimaera to become more active than VDAC1. (PMID:20434446)
• VDAC3 is present at the mother centriole and modulates centriole assembly by recruiting Mps1 to centrosomes. (PMID:22935710)
• VDAC 1, 2, and 3 recruit Parkin to defective mitochondria to promote mitochondrial autophagy. (PMID:23060438)
• a VDAC3-Mps1 module at the centrosome promotes ciliary disassembly during cell cycle entry. (PMID:23388454)
• observed electrophysiological properties of hVDAC3 are surprisingly different from the other isoforms and are discussed in relation to the proposed physiological role of the protein in mammalian cells (PMID:25171321)
• These data suggest that an interaction between Mcl-1 and VDAC promotes lung cancer cell migration by a mechanism that involves Ca(2+)-dependent reactive oxygen species production. (PMID:25341036)
• channel gating of VDAC3 might be controlled by redox sensing under physiological conditions (PMID:26407725)
• VDAC3 is able to modulate its pore size and current by exploiting the mobility of the N-terminal and forming, upon external stimuli, disulfide bridges with cysteine residues located on the barrel and exposed to the inter-membrane space. (PMID:26806159)
• The works available on VDAC cysteines support the notion that VDAC1, VDAC2, and VDAC3 proteins are paralogs with a similar pore-function and slightly different, but important, ancillary biological functions. (Review) (PMID:26947058)
• The AG genotype of rs16891278 showed a significantly lower sperm concentration compared with the AA genotype (P = 0.044). Findings suggest that VDAC3 genetic variants may be associated with human sperm count. (PMID:28431403)
• This cohort study showed that the VDAC3 gene was down regulation between patients with idiopathic Parkinson disease and controls (PMID:28916538)
• Data suggest that the hub genes NADH:ubiquinone oxidoreductase subunit B5 (NDUFB5), translocase of inner mitochondrial membrane domain containing 1 (TIMMDC1), and voltage-dependent anion channel 3 (VDAC3) might serve as potential biomarkers for diagnosis and/or therapeutic targets for precise treatment of septic cardiomyopathy (SC) . (PMID:31794266)
• A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology. (PMID:31935282)
• VDAC3 role in the melanoma drug resistance to erastin.Erastin-induced resistance mediated by FOXM1-Nedd4-VDAC2/VDAC3 negative feedback loop in melanoma.Nedd4 ubiquitinates and degrades VDAC3. (PMID:31974380)
• A High Resolution Mass Spectrometry Study Reveals the Potential of Disulfide Formation in Human Mitochondrial Voltage-Dependent Anion Selective Channel Isoforms (hVDACs). (PMID:32098132)
• Expression of voltage-dependent anion channels in endometrial cancer and its potential prognostic significance. (PMID:32829673)
• Specific Post-Translational Modifications of VDAC3 in ALS-SOD1 Model Cells Identified by High-Resolution Mass Spectrometry. (PMID:36555496)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	vdac3	ENSDARG00000003695
danio_rerio	zgc:56235	ENSDARG00000116680
mus_musculus	Vdac3	ENSMUSG00000008892
rattus_norvegicus	Vdac3	ENSRNOG00000019277
drosophila_melanogaster	porin	FBGN0004363
drosophila_melanogaster	Porin2	FBGN0069354
drosophila_melanogaster	CG17140	FBGN0260453
drosophila_melanogaster	CG17139	FBGN0260454

Paralogs (2): VDAC2 (ENSG00000165637), VDAC1 (ENSG00000213585)

Protein

Protein identifiers

Non-selective voltage-gated ion channel VDAC3 — Q9Y277 (reviewed: Q9Y277)

Alternative names: Outer mitochondrial membrane protein porin 3

All UniProt accessions (7): Q9Y277, E5RFL1, E5RFP6, E5RHE1, E5RHZ6, E5RJN6, E5RK27

UniProt curated annotations — full annotation on UniProt →

Function. Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane. Forms a high-conducting channel with a stable open state and a voltage-induced closure with a mild preference for anions over cations. Involved in male fertility and sperm mitochondrial sheath formation.

Subunit / interactions. Interacts with ARMC12 in a TBC1D21-dependent manner. Interacts with MISFA.

Subcellular location. Mitochondrion outer membrane. Membrane.

Tissue specificity. Expressed in erythrocytes (at protein level). Widely expressed. Highest in testis.

Post-translational modifications. Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.

Domain organisation. Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands.

Similarity. Belongs to the eukaryotic mitochondrial porin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y277-1	1	yes
Q9Y277-2	2

RefSeq proteins (12): NP_001129166, NP_001400481, NP_001400482, NP_001400483, NP_001400484, NP_001400485, NP_001400486, NP_001400487, NP_001400488, NP_001400489, NP_001400490, NP_005653* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001925	Porin_Euk	Family
IPR023614	Porin_dom_sf	Homologous_superfamily
IPR027246	Porin_Euk/Tom40	Family

Pfam: PF01459

Catalyzed reactions (Rhea), 2 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• chloride(in) = chloride(out) (RHEA:29823)

UniProt features (47 total): transmembrane region 19, binding site 8, modified residue 8, cross-link 7, short sequence motif 2, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y277-F1	95.26	0.94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 12; 20; 242; 243; 244; 261; 263; 264

Post-translational modifications (15): 2, 4, 12, 15, 20, 90, 241, 266, 53, 61, 109, 110, 163, 266, 274

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy
R-HSA-5689880	Ub-specific processing proteases
R-HSA-8949215	Mitochondrial calcium ion transport

MSigDB gene sets: 294 (showing top): MORF_DNMT1, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_COGNITION, GOBP_BEHAVIOR, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MORF_HDAC1, KYNG_DNA_DAMAGE_DN, MORF_HDAC2, GOBP_MALE_GAMETE_GENERATION, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_CELL_CELL_SIGNALING, GOBP_FEAR_RESPONSE, GOBP_NEURON_NEURON_SYNAPTIC_TRANSMISSION, KYNG_DNA_DAMAGE_BY_GAMMA_RADIATION

GO Biological Process (10): behavioral fear response (GO:0001662), neuron-neuron synaptic transmission (GO:0007270), spermatogenesis (GO:0007283), learning (GO:0007612), adenine transport (GO:0015853), sperm mitochondrial sheath assembly (GO:0120317), monoatomic ion transport (GO:0006811), chemical synaptic transmission (GO:0007268), transmembrane transport (GO:0055085), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (5): nucleotide binding (GO:0000166), voltage-gated monoatomic ion channel activity (GO:0005244), voltage-gated monoatomic anion channel activity (GO:0008308), porin activity (GO:0015288), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020), synapse (GO:0045202), pore complex (GO:0046930), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitophagy	1
Deubiquitination	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
intracellular membrane-bounded organelle	2
behavioral defense response	1
fear response	1
chemical synaptic transmission	1
developmental process involved in reproduction	1
male gamete generation	1
learning or memory	1
purine nucleobase transport	1
cellular component assembly	1
sperm flagellum assembly	1
anterograde trans-synaptic signaling	1
cellular process	1
monoatomic anion transport	1
monoatomic ion transmembrane transport	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
monoatomic ion channel activity	1
voltage-gated channel activity	1
voltage-gated monoatomic ion channel activity	1
monoatomic anion channel activity	1
wide pore channel activity	1
binding	1
cytoplasm	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1
cell junction	1
membrane protein complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

2810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VDAC3	GK2	Q14410	962
VDAC3	GK	P32189	960
VDAC3	CS	O75390	779
VDAC3	BCL2L1	Q07817	741
VDAC3	MCL1	Q07820	722
VDAC3	SLC25A4	P12235	660
VDAC3	VDAC2	P45880	629
VDAC3	BRAF	P15056	587
VDAC3	ATP5PD	O75947	566
VDAC3	CYCS	P00001	564
VDAC3	COX4I1	P13073	531
VDAC3	HRAS	P01112	524
VDAC3	TOMM22	Q9NS69	506
VDAC3	PPIF	P30405	504
VDAC3	PKM	P14618	504

IntAct

131 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
VDAC1	VDAC3	psi-mi:“MI:0915”(physical association)	0.670
NME3	NME4	psi-mi:“MI:0914”(association)	0.640
VDAC2	VDAC3	psi-mi:“MI:0915”(physical association)	0.560
VDAC1	HK1	psi-mi:“MI:0914”(association)	0.560
VDAC3	HRAS	psi-mi:“MI:0914”(association)	0.530
SPATA19	MTHFR	psi-mi:“MI:0914”(association)	0.530
FAM8A1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
env	FLOT1	psi-mi:“MI:0914”(association)	0.460
RIF1	VDAC3	psi-mi:“MI:0915”(physical association)	0.400
ZNF365	VDAC3	psi-mi:“MI:0915”(physical association)	0.400
VDAC3	ZNF227	psi-mi:“MI:0915”(physical association)	0.400
HIRIP3	VDAC3	psi-mi:“MI:0915”(physical association)	0.400
Tubb4b	MGST3	psi-mi:“MI:0915”(physical association)	0.400
ACTB	DDX3X	psi-mi:“MI:0915”(physical association)	0.400
DHRS2	GAPDH	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
PCNA	VDAC3	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Rmdn3	DERL1	psi-mi:“MI:0914”(association)	0.350
Jmy	PHGDH	psi-mi:“MI:0914”(association)	0.350
	TUBA4A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
COX15	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350

BioGRID (456): VDAC3 (Affinity Capture-MS), VDAC3 (Affinity Capture-MS), VDAC3 (Affinity Capture-MS), VDAC3 (Affinity Capture-MS), VDAC3 (Affinity Capture-MS), VDAC3 (Affinity Capture-MS), ATP5A1 (Co-fractionation), ATP5B (Co-fractionation), ATP5C1 (Co-fractionation), ATP5D (Co-fractionation), ATP5H (Co-fractionation), ATP5I (Co-fractionation), ATP5O (Co-fractionation), ATP6V0D1 (Co-fractionation), ATP6V1A (Co-fractionation)

ESM2 similar proteins: A0A1S4A695, A0A6P7EFR0, A4F267, A6QR22, O97556, P07144, P21796, P42055, P42056, P45879, P45880, P50395, P50397, P50399, P62495, P62496, P62497, P62498, P68002, P68003, P81004, P81155, P82013, P86223, Q0VCK5, Q0VCX5, Q1W374, Q1W375, Q1W376, Q1W377, Q29380, Q5R4C7, Q5R7V4, Q5RCE1, Q5U2Q7, Q60930, Q60931, Q60932, Q61598, Q6Q7J2

Diamond homologs: A0A6P7EFR0, P07144, P21796, P45879, P45880, P68002, P68003, P81004, P81155, P82013, P82945, P83781, P86223, Q21752, Q29380, Q5R7V4, Q60930, Q60931, Q60932, Q94920, Q9MZ13, Q9MZ15, Q9MZ16, Q9R1Z0, Q9TT13, Q9TT15, Q9Y277, Q9Z2L0, Q9P544, P04840, P40478, Q7F4F8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 178 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by high-kinase activity BRAF mutants	5	13.3×	5e-03
MAP2K and MAPK activation	5	12.0×	5e-03
Signaling by RAF1 mutants	5	11.7×	5e-03
Signaling by moderate kinase activity BRAF mutants	5	10.7×	5e-03
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	10.7×	5e-03
Signaling downstream of RAS mutants	5	10.7×	5e-03
Signaling by BRAF and RAF1 fusions	6	8.6×	5e-03
Innate Immune System	14	3.0×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	5	20.1×	2e-03
mRNA stabilization	6	14.7×	2e-03
Ras protein signal transduction	7	9.6×	3e-03
axonogenesis	8	8.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

39 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1517 predictions. Top by Δscore:

Variant	Effect	Δscore
8:42392034:G:GT	donor_gain	1.0000
8:42394194:T:TA	acceptor_gain	1.0000
8:42394205:A:AG	acceptor_gain	1.0000
8:42394206:T:G	acceptor_gain	1.0000
8:42394207:A:AG	acceptor_gain	1.0000
8:42394207:AAG:A	acceptor_loss	1.0000
8:42394208:A:AG	acceptor_loss	1.0000
8:42394208:A:G	acceptor_gain	1.0000
8:42394209:GATAT:G	acceptor_gain	1.0000
8:42394274:ATATG:A	donor_gain	1.0000
8:42394275:TATG:T	donor_gain	1.0000
8:42394277:TG:T	donor_gain	1.0000
8:42394278:GG:G	donor_gain	1.0000
8:42394279:G:GA	donor_loss	1.0000
8:42394279:G:GG	donor_gain	1.0000
8:42395134:G:T	donor_loss	1.0000
8:42395135:T:G	donor_loss	1.0000
8:42395136:GA:G	donor_loss	1.0000
8:42395137:AGT:A	donor_loss	1.0000
8:42398709:CA:C	acceptor_loss	1.0000
8:42398710:A:AG	acceptor_gain	1.0000
8:42398710:A:AT	acceptor_loss	1.0000
8:42398711:G:A	acceptor_loss	1.0000
8:42398711:G:GG	acceptor_gain	1.0000
8:42398711:GGA:G	acceptor_gain	1.0000
8:42399702:GG:G	donor_gain	1.0000
8:42399703:GG:G	donor_gain	1.0000
8:42401781:A:AG	acceptor_gain	1.0000
8:42401783:TGCA:T	acceptor_loss	1.0000
8:42401785:CAG:C	acceptor_loss	1.0000

AlphaMissense

1853 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:42398817:T:A	W75R	0.999
8:42398817:T:C	W75R	0.999
8:42403327:T:C	F190L	0.998
8:42403329:T:A	F190L	0.998
8:42403329:T:G	F190L	0.998
8:42403376:T:A	I206K	0.998
8:42401919:G:A	G152D	0.996
8:42403336:T:C	S193P	0.996
8:42403387:T:A	W210R	0.996
8:42403387:T:C	W210R	0.996
8:42403424:C:A	A222D	0.996
8:42404868:C:A	A235D	0.996
8:42398767:T:C	L58P	0.995
8:42402015:T:A	V184E	0.995
8:42403376:T:G	I206R	0.995
8:42403382:T:C	L208P	0.995
8:42404872:A:C	K236N	0.995
8:42404872:A:T	K236N	0.995
8:42404892:T:A	I243N	0.995
8:42394242:G:A	G11R	0.994
8:42394242:G:C	G11R	0.994
8:42395102:T:A	I29K	0.994
8:42398716:T:C	F41S	0.994
8:42398761:G:A	G56D	0.994
8:42401909:T:A	W149R	0.994
8:42401909:T:C	W149R	0.994
8:42402003:T:C	L180P	0.994
8:42403415:T:C	F219S	0.994
8:42404867:G:C	A235P	0.994
8:42404874:T:A	V237E	0.994

dbSNP variants (sampled 300 via entrez): RS1000306647 (8:42393060 C>G), RS1000356617 (8:42393028 T>C), RS1000443456 (8:42392749 C>A,G), RS1000638835 (8:42395155 A>G), RS1000720408 (8:42391887 A>C,G,T), RS1000914297 (8:42398731 A>G), RS1000914837 (8:42402135 C>G,T), RS1001700985 (8:42399932 A>G), RS1001771730 (8:42400113 G>A), RS1001787646 (8:42392214 C>G,T), RS1001901996 (8:42391496 G>A,C), RS1001971624 (8:42401714 T>G), RS1002196736 (8:42394510 A>G), RS1002327342 (8:42394090 A>G), RS1002529553 (8:42404441 C>T)

Disease associations

OMIM: gene MIM:610029 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523505 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.63	Kd	23.32	nM	CHEMBL5653589
7.63	ED50	23.32	nM	CHEMBL5653589
6.13	Kd	744.5	nM	CHEMBL3752910
6.13	ED50	744.5	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149762: Binding affinity to human VDAC3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0233	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149762: Binding affinity to human VDAC3 incubated for 45 mins by Kinobead based pull down assay	kd	0.7446	uM

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, decreases expression, increases expression	2
bisphenol A	increases expression	2
Acetaminophen	increases expression	2
Valproic Acid	affects expression, increases expression	2
1-Methyl-4-phenylpyridinium	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
geldanamycin	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erastin	decreases expression, affects response to substance	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases secretion	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4341392	Binding	Binding affinity to VDAC3 in human A549 cells lysates grown on SILAC media at 10 uM incubated for 1 hr by LC-MS/MS analysis	Profiling withanolide A for therapeutic targets in neurodegenerative diseases. — Bioorg Med Chem

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3L7	Abcam HEK293T VDAC3 KO	Transformed cell line	Female
CVCL_D8DC	Ubigene A-549 VDAC3 KO	Cancer cell line	Male
CVCL_D8Y2	Ubigene HCT 116 VDAC3 KO	Cancer cell line	Male
CVCL_D9VL	Ubigene HEK293 VDAC3 KO	Transformed cell line	Female
CVCL_E0SS	Ubigene HeLa VDAC3 KO	Cancer cell line	Female
CVCL_TX38	HAP1 VDAC3 (-) 1	Cancer cell line	Male
CVCL_XU98	HAP1 VDAC3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.