VAMP8

Summary

VAMP8 (vesicle associated membrane protein 8, HGNC:12647) is a protein-coding gene on chromosome 2p11.2, encoding Vesicle-associated membrane protein 8 (Q9BV40). SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes.

This gene encodes an integral membrane protein that belongs to the synaptobrevin/vesicle-associated membrane protein subfamily of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The encoded protein is involved in the fusion of synaptic vesicles with the presynaptic membrane.

Source: NCBI Gene 8673 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 18 total
• Druggable target: yes
• MANE Select transcript: NM_003761

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12647
Approved symbol	VAMP8
Name	vesicle associated membrane protein 8
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	EDB, VAMP-8
Ensembl gene	ENSG00000118640
Ensembl biotype	protein_coding
OMIM	603177
Entrez	8673

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000263864, ENST00000409760, ENST00000432071, ENST00000863237, ENST00000863238, ENST00000915989

RefSeq mRNA: 1 — MANE Select: NM_003761 NM_003761

CCDS: CCDS1979

Canonical transcript exons

ENST00000263864 — 3 exons

Exon	Start	End
ENSE00001076027	85577586	85577649
ENSE00003685402	85581576	85582031
ENSE00003686468	85579009	85579167

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.9282 / max 844.9744, expressed in 1330 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21217	44.9282	1330

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.47	gold quality
monocyte	CL:0000576	99.46	gold quality
mononuclear cell	CL:0000842	99.41	gold quality
leukocyte	CL:0000738	99.39	gold quality
mucosa of transverse colon	UBERON:0004991	99.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.33	gold quality
granulocyte	CL:0000094	99.32	gold quality
jejunal mucosa	UBERON:0000399	99.30	gold quality
esophagus squamous epithelium	UBERON:0006920	99.19	gold quality
lower esophagus mucosa	UBERON:0035834	99.18	gold quality
rectum	UBERON:0001052	99.16	gold quality
nasal cavity epithelium	UBERON:0005384	99.12	gold quality
bronchial epithelial cell	CL:0002328	99.08	gold quality
epithelium of bronchus	UBERON:0002031	99.08	gold quality
nasal cavity mucosa	UBERON:0001826	99.05	gold quality
bronchus	UBERON:0002185	99.04	gold quality
esophagus mucosa	UBERON:0002469	98.99	gold quality
skin of abdomen	UBERON:0001416	98.93	gold quality
minor salivary gland	UBERON:0001830	98.89	gold quality
right lung	UBERON:0002167	98.87	gold quality
body of pancreas	UBERON:0001150	98.86	gold quality
metanephros cortex	UBERON:0010533	98.86	gold quality
upper lobe of left lung	UBERON:0008952	98.84	gold quality
penis	UBERON:0000989	98.79	gold quality
saliva-secreting gland	UBERON:0001044	98.78	gold quality
upper lobe of lung	UBERON:0008948	98.77	gold quality
duodenum	UBERON:0002114	98.76	gold quality
mouth mucosa	UBERON:0003729	98.76	gold quality
oral cavity	UBERON:0000167	98.75	gold quality
skin of leg	UBERON:0001511	98.64	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	1233.25
E-MTAB-9388	yes	818.85
E-HCAD-6	yes	745.13
E-MTAB-7008	yes	585.09
E-HCAD-1	yes	89.51
E-HCAD-4	yes	75.14
E-HCAD-10	yes	54.43
E-MTAB-8410	yes	53.73
E-CURD-122	yes	53.26
E-GEOD-135922	yes	52.68
E-MTAB-10287	yes	45.19
E-CURD-46	yes	40.20
E-CURD-112	yes	37.15
E-GEOD-134144	yes	31.87
E-MTAB-10553	yes	28.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting VAMP8, 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-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-711	96.60	65.75	528
HSA-MIR-4524B-3P	95.52	64.12	964

Literature-anchored findings (GeneRIF, showing 34)

• VAMP-3 and VAMP-8 are present in human platelets and are required for granule secretion. (PMID:12130530)
• Our findings indicate that VAMP5 and VAMP8 are not involved in POAG in the Dutch population. (PMID:16110299)
• VAMP-8 is unlikely to be a v-SNARE for constitutive exocytosis in HSY cells. (PMID:16195891)
• Variants in 2 genes were associated with early-onset myocardial infarct: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. (PMID:16690874)
• Data show that mature human mast cells express a specific pattern of SNARE and that VAMP-7 and VAMP-8, but not VAMP-2, are required for rapid degranulation. (PMID:18253931)
• Results report that syntaxin 7, syntaxin 8, vti1b and VAMP8 physically and functionally interact with CFTR. (PMID:18570918)
• A putative association between a VAMP8 gene variant and platelet functions ex vivo, was tested. (PMID:19374688)
• VAMP8 is not essential for constitutive exocytosis, although it can be involved in the exocytosis (PMID:19738360)
• Support a role for VAMP8/endobrevin in the heterogeneity of platelet reactivity, and suggest a role for microRNA-96 in the regulation of VAMP8 expression. (PMID:19943878)
• Results suggest that the combinational SNARE proteins VAMP8 and Vti1b mediate the fusion of antimicrobial and canonical autophagosomes with lysosomes, an essential event for autophagic degradation. (PMID:20089838)
• The VAMP8 rs1010 polymorphism was associated with CHD risk in Chinese Han population, the A allele might serve as a genetic risk factor of coronary heart disease. (PMID:20533276)
• Dynamics of FIP3- and VAMP8-containing endosomes reflect the progressive stages of abscission. (PMID:21486954)
• VAMP8 regulates mucin granule exocytosis in airway goblet cells, and reduction of its expression may provide a novel therapeutic target to ameliorate airway mucus obstruction in lung diseases (PMID:22144578)
• Assessment of KIF6 genotype is not useful in predicting low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly. (PMID:22192511)
• Inhibition of VAMP8, but not VAMP7, significantly reduces viral entry. (PMID:24550300)
• Vesicle-associated membrane protein 8 as a novel oncogene by promoting cell proliferation and therapeutic resistance in glioma. Targeting VAMP8 may serve as a potential therapeutic regimen for the treatment of glioma. (PMID:25209430)
• Starvation-induced MTMR13 and RAB21 activity regulates VAMP8 to promote autophagosome-lysosome fusion. (PMID:25648148)
• Cytotoxic granule exocytosis is a sequential, multivesicle fusion process requiring VAMP8-mediated recycling endosome fusion before cytotoxic granule fusion. (PMID:26124288)
• our study suggested that VAMP8 gene variants might not contribute to glioma susceptibility and associated with glioma in the Chinese Han population. (PMID:26191281)
• Findings indicate that patients with low vesicle associated membrane protein 8 (VAMP8)/low rab GTP-binding protein RAB37 (RAB37) expression profile showed significantly high risk of death even after adjusting for tumor metastasis parameter. (PMID:30165196)
• data show that defects in adaptor protein complex 3-dependent maturation of Weibel-Palade bodies impairs exocytosis by affecting the recruitment of VAMP8. (PMID:30630984)
• autophagic degradation critically determines the production of HBV virions and HBsAg; this is controlled by the SNAP29-VAMP8 interaction (PMID:30742775)
• The rs1010 SNP genotypes AG (p = 0.028) and GG (p = 0.016) were associated with increased susceptibility to Pulmonary Tuberculosis. (PMID:30945947)
• these results provide evidence that TRIM6 contributes to the antiviral response against WNV and identify VAMP8 as a novel regulator of the IFN-I system. (PMID:31694946)
• Association of KLK3, VAMP8 and MDM4 Genetic Variants within microRNA Binding Sites with Prostate Cancer: Evidence from Serbian Population. (PMID:32556890)
• Decoding three distinct states of the Syntaxin17 SNARE motif in mediating autophagosome-lysosome fusion. (PMID:32817423)
• Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway. (PMID:34042162)
• Prefused lysosomes cluster on autophagosomes regulated by VAMP8. (PMID:34645799)
• Stimulating TRPM7 suppresses cancer cell proliferation and metastasis by inhibiting autophagy. (PMID:34752845)
• mTOR-mediated phosphorylation of VAMP8 and SCFD1 regulates autophagosome maturation. (PMID:34785650)
• Oxidative Stress Impairs Autophagy via Inhibition of Lysosomal Transport of VAMP8. (PMID:36328496)
• VAMP8 suppresses the metastasis via DDX5/beta-catenin signal pathway in osteosarcoma. (PMID:37405957)
• The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome-lysosome fusion. (PMID:38182888)
• Vesicle-associated membrane protein 8 knockdown exerts anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on colorectal cancer cells by inhibition of the JAK/STAT3 pathway. (PMID:38720136)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vamp8	ENSDARG00000024116
mus_musculus	Vamp8	ENSMUSG00000050732
rattus_norvegicus	Vamp8	ENSRNOG00000012748
caenorhabditis_elegans		WBGENE00007200

Paralogs (10): VAMP3 (ENSG00000049245), SEC22C (ENSG00000093183), YKT6 (ENSG00000106636), VAMP4 (ENSG00000117533), SEC22A (ENSG00000121542), VAMP7 (ENSG00000124333), VAMP1 (ENSG00000139190), VAMP5 (ENSG00000168899), VAMP2 (ENSG00000220205), SEC22B (ENSG00000265808)

Protein

Protein identifiers

Vesicle-associated membrane protein 8 — Q9BV40 (reviewed: Q9BV40)

Alternative names: Endobrevin

All UniProt accessions (3): Q9BV40, B8ZZT4, C9JXZ5

UniProt curated annotations — full annotation on UniProt →

Function. SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t-SNARE complex. Also required for dense-granule secretion in platelets. Also plays a role in regulated enzyme secretion in pancreatic acinar cells. Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells. Involved in the homotypic fusion of early and late endosomes. Also participates in the activation of type I interferon antiviral response through a TRIM6-dependent mechanism.

Subunit / interactions. Forms a SNARE complex composed of VAMP8, SNAP29 and STX17 involved in fusion of autophagosome with lysosome. Found in a number of SNARE complexes with NAPA, SNAP23, SNAP25, STX1A, STX4, STX7, STX8 and VTI1B. Interacts with PICALM. SNARE complex formation and binding by PICALM are mutually exclusive processes for VAMP8. Interacts with SBF2/MTMR13. Interacts with RAB21 (in GTP-bound form) in response to starvation; the interaction probably regulates VAMP8 endolysosomal trafficking. Interacts with STX17; this interaction is increased in the absence of TMEM39A. Interacts with TRIM6. Interacts with RAB44; VAMP8 may act as RAB44 effector in mast cell degranulation. (Microbial infection) The interaction with STX17 is decreased in presence of SARS coronavirus-2/SARS-CoV-2 ORF3A protein.

Subcellular location. Lysosome membrane. Early endosome membrane. Late endosome membrane. Cell membrane. Zymogen granule membrane.

Tissue specificity. Platelets.

Post-translational modifications. (Microbial infection) Stearoylated By S.flexneri N-epsilon-fatty acyltransferase IcsB, thereby disrupting the host actin cytoskeleton.

Similarity. Belongs to the synaptobrevin family.

RefSeq proteins (1): NP_003752* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001388	Synaptobrevin-like	Family
IPR016444	Synaptobrevin/VAMP	Family
IPR042855	V_SNARE_CC	Domain

Pfam: PF00957

UniProt features (20 total): modified residue 7, topological domain 2, lipid moiety-binding region 2, mutagenesis site 2, sequence conflict 2, chain 1, helix 1, transmembrane region 1, domain 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4WY4	X-RAY DIFFRACTION	1.4
7BV6	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV40-F1	90.56	0.79

Functional residue map

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

Catalytic / active sites (1): 33 (interaction with stx8)

Post-translational modifications (9): 48, 54, 55, 64, 68, 1, 5, 18, 28

Mutagenesis-validated functional residues (2):

Position	Phenotype
64–68	abolished stearoylation in response to s.flexneri infection.
72	does not affect stearoylation in response to s.flexneri infection.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-432720	Lysosome Vesicle Biogenesis
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-6798695	Neutrophil degranulation
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 399 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GOBP_VESICLE_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_MEMBRANE_FUSION, DITTMER_PTHLH_TARGETS_UP, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (14): vesicle fusion (GO:0006906), protein transport (GO:0015031), autophagosome membrane docking (GO:0016240), SNARE complex assembly (GO:0035493), symbiont entry into host cell (GO:0046718), defense response to virus (GO:0051607), mucus secretion (GO:0070254), autophagosome maturation (GO:0097352), regulation of protein localization to plasma membrane (GO:1903076), negative regulation of secretion by cell (GO:1903531), positive regulation of histamine secretion by mast cell (GO:1903595), autophagy (GO:0006914), vesicle-mediated transport (GO:0016192), protein-containing complex organization (GO:0043933)

GO Molecular Function (4): SNAP receptor activity (GO:0005484), chloride channel inhibitor activity (GO:0019869), syntaxin binding (GO:0019905), protein binding (GO:0005515)

GO Cellular Component (26): cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), secretory granule membrane (GO:0030667), clathrin-coated endocytic vesicle membrane (GO:0030669), phagocytic vesicle membrane (GO:0030670), SNARE complex (GO:0031201), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), vesicle (GO:0031982), azurophil granule membrane (GO:0035577), specific granule membrane (GO:0035579), zymogen granule membrane (GO:0042589), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), mucin granule (GO:0098594), lysosome (GO:0005764), endosome (GO:0005768), endomembrane system (GO:0012505), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Membrane Trafficking	2
trans-Golgi Network Vesicle Budding	2
Antigen processing-Cross presentation	1
Innate Immune System	1
Clathrin-mediated endocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
endosome membrane	3
secretory granule membrane	3
transport	2
endosome	2
endocytic vesicle membrane	2
vesicle organization	1
vesicle-mediated transport	1
organelle membrane fusion	1
intracellular protein localization	1
establishment of protein localization	1
autophagosome maturation	1
organelle localization by membrane tethering	1
vesicle fusion	1
protein-containing complex assembly	1
viral life cycle	1
symbiont entry into host	1
defense response	1
response to virus	1
body fluid secretion	1
secretion by tissue	1
macroautophagy	1
protein-containing complex disassembly	1
protein localization to plasma membrane	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
secretion by cell	1
negative regulation of cellular process	1
negative regulation of secretion	1
regulation of secretion by cell	1
histamine secretion by mast cell	1
positive regulation of mast cell degranulation	1
positive regulation of hormone secretion	1
positive regulation of inflammatory response	1
positive regulation of multicellular organismal process	1
regulation of histamine secretion by mast cell	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1

Protein interactions and networks

STRING

1863 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VAMP8	SNAP23	O00161	999
VAMP8	STX4	Q12846	999
VAMP8	SNAP29	O95721	998
VAMP8	STX17	P56962	998
VAMP8	STX7	O15400	998
VAMP8	VTI1B	Q9UEU0	996
VAMP8	STX3	Q13277	994
VAMP8	STX8	Q9UNK0	994
VAMP8	VAMP7	P51809	990
VAMP8	STX2	P32856	959
VAMP8	ATG14	Q6ZNE5	947
VAMP8	STX6	O43752	941
VAMP8	STX11	O75558	929
VAMP8	STX1B	P61266	886
VAMP8	SNAP25	P13795	870

IntAct

102 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
STX4	VAMP3	psi-mi:“MI:0915”(physical association)	0.880
SNAP29	VAMP8	psi-mi:“MI:0915”(physical association)	0.830
VAMP8	SNAP29	psi-mi:“MI:0914”(association)	0.830
STX17	SNAP29	psi-mi:“MI:0914”(association)	0.810
SNAP29	STX17	psi-mi:“MI:0914”(association)	0.810
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
STX17	VAMP8	psi-mi:“MI:0915”(physical association)	0.740
VAMP8	STX17	psi-mi:“MI:0915”(physical association)	0.740
STX17	VAMP8	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
VAMP8	STX7	psi-mi:“MI:0915”(physical association)	0.670
STX6	GOSR2	psi-mi:“MI:0914”(association)	0.670
VAMP8	STX7	psi-mi:“MI:0914”(association)	0.670

BioGRID (184): STX6 (Affinity Capture-Western), STX7 (Affinity Capture-Western), STX8 (Affinity Capture-Western), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Proximity Label-MS), VAMP8 (Affinity Capture-MS), VAMP8 (Affinity Capture-Western)

ESM2 similar proteins: G3V7P1, O02495, O09044, O15400, O49377, O70257, O70377, O70404, O70439, O70480, O75379, O88384, O95183, P31109, P33328, P47193, P51809, P58200, P63024, P63025, P63026, P63027, P63045, P70280, Q15836, Q17QI5, Q2KHY2, Q2KIU0, Q2KJD2, Q32L97, Q3T0Y8, Q3ZBT5, Q4R8T0, Q5R602, Q5RBW6, Q5REQ5, Q5RF94, Q5ZL74, Q60WU2, Q86Y82

Diamond homologs: O02495, O48850, O49377, O70404, O70480, O75379, O95183, P13701, P18489, P23763, P31109, P33328, P34351, P35589, P47192, P47193, P47194, P63024, P63025, P63026, P63027, P63044, P63045, Q0V7N0, Q12255, Q15836, Q27236, Q2KHY2, Q2KJD2, Q32L97, Q3T0Y8, Q4R8T0, Q5REQ5, Q60WU2, Q62442, Q63666, Q6TMJ9, Q92356, Q9BV40, Q9FMR5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
VAMP8	“form complex”	“STX11-VAMP8 SNARE complex”	binding
MARCHF9	“down-regulates quantity by destabilization”	VAMP8	ubiquitination
VAMP8	“form complex”	“STX17-VAMP8 SNARE complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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
Intra-Golgi traffic	8	42.4×	6e-10
trans-Golgi Network Vesicle Budding	6	31.1×	2e-06
Retrograde transport at the Trans-Golgi-Network	5	22.4×	7e-05
Golgi Associated Vesicle Biogenesis	5	20.4×	1e-04
COPII-mediated vesicle transport	6	20.0×	2e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	15.8×	3e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	7	15.0×	1e-05
COPI-mediated anterograde transport	6	13.4×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	9	113.0×	6e-15
vesicle fusion	10	98.7×	1e-15
membrane fusion	8	81.9×	4e-12
obsolete vesicle docking involved in exocytosis	5	55.2×	2e-06
intra-Golgi vesicle-mediated transport	5	43.2×	5e-06
exocytosis	10	24.9×	6e-10
cellular response to type II interferon	5	17.1×	4e-04
intracellular protein transport	16	17.0×	1e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

480 predictions. Top by Δscore:

Variant	Effect	Δscore
2:85579004:CACA:C	acceptor_loss	1.0000
2:85579153:G:GT	donor_gain	1.0000
2:85579159:G:GT	donor_gain	1.0000
2:85579168:G:GG	donor_gain	1.0000
2:85581574:A:AG	acceptor_gain	1.0000
2:85581575:G:GC	acceptor_gain	1.0000
2:85581575:GT:G	acceptor_gain	1.0000
2:85581575:GTC:G	acceptor_gain	1.0000
2:85581575:GTCT:G	acceptor_gain	1.0000
2:85579007:A:AG	acceptor_gain	0.9900
2:85579007:AG:A	acceptor_gain	0.9900
2:85579007:AGGAG:A	acceptor_gain	0.9900
2:85579008:G:GG	acceptor_gain	0.9900
2:85579008:GG:G	acceptor_gain	0.9900
2:85579008:GGA:G	acceptor_gain	0.9900
2:85579008:GGAGG:G	acceptor_gain	0.9900
2:85579159:G:T	donor_gain	0.9900
2:85579164:CACA:C	donor_gain	0.9900
2:85579165:ACA:A	donor_gain	0.9900
2:85579166:CA:C	donor_gain	0.9900
2:85579167:AGTG:A	donor_loss	0.9900
2:85579168:G:T	donor_loss	0.9900
2:85579169:T:A	donor_loss	0.9900
2:85579177:G:GT	donor_gain	0.9900
2:85579177:G:T	donor_gain	0.9900
2:85579178:G:T	donor_gain	0.9900
2:85579206:G:GT	donor_gain	0.9900
2:85579207:G:T	donor_gain	0.9900
2:85581572:ACAG:A	acceptor_loss	0.9900
2:85581573:CA:C	acceptor_loss	0.9900

AlphaMissense

659 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:85579136:T:C	L44P	0.997
2:85581597:T:C	S62P	0.997
2:85581598:C:G	S62W	0.997
2:85581576:T:C	S55P	0.996
2:85581577:C:T	S55F	0.996
2:85579162:G:C	A53P	0.995
2:85581613:G:C	R67P	0.995
2:85579094:A:T	N30I	0.994
2:85579111:G:C	A36P	0.994
2:85579157:T:C	L51P	0.994
2:85581609:G:C	A66P	0.994
2:85579103:G:C	R33P	0.992
2:85579109:T:C	L35P	0.992
2:85579115:G:C	R37P	0.992
2:85581585:T:C	F58L	0.992
2:85581587:C:A	F58L	0.992
2:85581587:C:G	F58L	0.992
2:85581654:T:C	C81R	0.992
2:85579052:T:C	L16P	0.991
2:85581586:T:C	F58S	0.991
2:85579139:G:C	R45P	0.990
2:85579148:C:T	T48I	0.989
2:85579095:T:A	N30K	0.988
2:85579095:T:G	N30K	0.988
2:85581577:C:A	S55Y	0.988
2:85581586:T:G	F58C	0.987
2:85579085:T:A	M27K	0.985
2:85579117:G:T	G38W	0.985
2:85579136:T:A	L44H	0.985
2:85579093:A:T	N30Y	0.982

dbSNP variants (sampled 300 via entrez): RS1000301061 (2:85580100 A>AC), RS1000489462 (2:85580608 G>A,C,T), RS1000863621 (2:85579693 A>G), RS1001229985 (2:85581484 A>AAT), RS1001304016 (2:85579350 A>C,G), RS1001670923 (2:85580130 T>G), RS1001741939 (2:85580525 G>T), RS1002218706 (2:85578643 G>T), RS1003480606 (2:85578279 A>G), RS1004075428 (2:85581231 G>A,C), RS1004367784 (2:85579395 G>A), RS1004433308 (2:85579671 C>A,G,T), RS1005373131 (2:85580989 G>C), RS1005445336 (2:85581304 ACCT>A), RS1005484039 (2:85579744 A>G)

Disease associations

OMIM: gene MIM:603177 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001148_4	Prostate cancer	3.000000e-15
GCST003116_32	Coronary artery disease	4.000000e-10
GCST003117_3	Myocardial infarction	3.000000e-10
GCST004606_59	Eosinophil count	4.000000e-09
GCST004624_66	Sum eosinophil basophil counts	5.000000e-10
GCST004787_22	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2.000000e-13
GCST005196_204	Coronary artery disease	2.000000e-23
GCST010479_58	Coronary artery disease	4.000000e-11
GCST90002381_33	Eosinophil count	3.000000e-13
GCST90002382_40	Eosinophil percentage of white cells	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066312 (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
5.74	Kd	1835	nM	CHEMBL3752910
5.74	ED50	1835	nM	CHEMBL3752910
5.34	Kd	4589	nM	CHEMBL5653589
5.34	ED50	4589	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149752: Binding affinity to human VAMP8 incubated for 45 mins by Kinobead based pull down assay	kd	1.8352	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149752: Binding affinity to human VAMP8 incubated for 45 mins by Kinobead based pull down assay	kd	4.5895	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	7
(+)-JQ1 compound	decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
sodium arsenite	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
3-nitrobenzanthrone	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
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
clothianidin	increases expression	1
nutlin 3	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652794	Binding	Binding affinity to human VAMP8 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1CQ	Abcam A-431 VAMP8 KO	Cancer cell line	Female
CVCL_B3L4	Abcam HEK293T VAMP8 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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