VAMP3

Summary

VAMP3 (vesicle associated membrane protein 3, HGNC:12644) is a protein-coding gene on chromosome 1p36.23, encoding Vesicle-associated membrane protein 3 (Q15836). SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network.

Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. This gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Because of its high homology to other known VAMPs, its broad tissue distribution, and its subcellular localization, the protein encoded by this gene was shown to be the human equivalent of the rodent cellubrevin. In platelets the protein resides on a compartment that is not mobilized to the plasma membrane on calcium or thrombin stimulation.

Source: NCBI Gene 9341 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_004781

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12644
Approved symbol	VAMP3
Name	vesicle associated membrane protein 3
Location	1p36.23
Locus type	gene with protein product
Status	Approved
Aliases	CEB
Ensembl gene	ENSG00000049245
Ensembl biotype	protein_coding
OMIM	603657
Entrez	9341

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000054666, ENST00000470357, ENST00000487194

RefSeq mRNA: 1 — MANE Select: NM_004781 NM_004781

CCDS: CCDS88

Canonical transcript exons

ENST00000054666 — 5 exons

Exon	Start	End
ENSE00001474288	7779626	7781432
ENSE00001474297	7771296	7771385
ENSE00003491204	7773442	7773511
ENSE00003607081	7778118	7778169
ENSE00003671151	7777160	7777318

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 112.7057 / max 2592.6961, expressed in 1826 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
437	112.7057	1826

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior olivary complex	UBERON:0002127	99.23	gold quality
parietal pleura	UBERON:0002400	99.07	gold quality
visceral pleura	UBERON:0002401	99.02	gold quality
cranial nerve II	UBERON:0000941	98.98	gold quality
pleura	UBERON:0000977	98.86	gold quality
gingival epithelium	UBERON:0001949	98.85	gold quality
gingiva	UBERON:0001828	98.70	gold quality
inferior vagus X ganglion	UBERON:0005363	98.68	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.61	gold quality
palpebral conjunctiva	UBERON:0001812	98.59	gold quality
spinal cord	UBERON:0002240	98.56	gold quality
trabecular bone tissue	UBERON:0002483	98.47	gold quality
eye	UBERON:0000970	98.37	gold quality
oocyte	CL:0000023	98.36	gold quality
medial globus pallidus	UBERON:0002477	98.36	gold quality
globus pallidus	UBERON:0001875	98.33	gold quality
renal glomerulus	UBERON:0000074	98.28	gold quality
upper leg skin	UBERON:0004262	98.21	gold quality
subthalamic nucleus	UBERON:0001906	98.19	gold quality
tongue squamous epithelium	UBERON:0006919	98.17	gold quality
mammalian vulva	UBERON:0000997	98.16	gold quality
cauda epididymis	UBERON:0004360	98.16	gold quality
metanephric glomerulus	UBERON:0004736	98.14	gold quality
squamous epithelium	UBERON:0006914	98.11	gold quality
secondary oocyte	CL:0000655	98.09	gold quality
esophagus squamous epithelium	UBERON:0006920	98.07	gold quality
olfactory bulb	UBERON:0002264	98.03	gold quality
adult organism	UBERON:0007023	98.03	gold quality
hair follicle	UBERON:0002073	97.97	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-13	no	2.96
E-MTAB-9543	no	2.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting VAMP3, 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-4533	100.00	69.48	2758
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-2682-5P	99.73	67.38	1055

Literature-anchored findings (GeneRIF, showing 22)

• Hyperacidification of cellubrevin endocytic compartments and defective endosomal recycling in cystic fibrosis respiratory epithelial cells (PMID:11809765)
• VAMP-3 and VAMP-8 are present in human platelets and are required for granule secretion. (PMID:12130530)
• These results do not suggest that a common genetic variant at VAMP2 or VAMP3 contributes to the development of bipolar affective disorder in German patients. (PMID:18628682)
• VAMP3-dependent integrin trafficking is crucial in cell migration and cell adhesion to laminin. (PMID:19159614)
• TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. (PMID:19781582)
• the importance of VAMP3 in the trafficking of matrix metalloproteinases during degradation of extracellular matrix substrates and subsequent cellular invasion (PMID:19910495)
• Endothelial cells specifically select VAMP 3 over VAMP8 to cooperate with syntaxin 4 and SNAP23 in the Ca(2+)-triggered fusion of Weibel-Palade bodies with the plasma membrane. (PMID:21094665)
• Data suggest a new integrin trafficking pathway in which endocytosed integrins are transported from VAMP3-containing recycling endosomes to STX6-containing trans-Golgi network before being recycled to the plasma membrane. (PMID:22573826)
• mutation of the Godzilla ubiquitylation target lysines on VAMP3 abrogates the formation of enlarged endosomes induced by either Godzilla or RNF167. (PMID:23353890)
• Genome-wide expression profiling identified the transcription of ADIPOR1, VAMP3 and C11ORF10 to be correlated with decreased ANRIL expression in a time-dependent manner. (PMID:23813974)
• Data suggest VAMP3 and SNAP23 (synaptosomal-associated protein 23 kDa) participate in interleukin-1beta-, interleukin-1 receptor-, calcium signaling-dependent secretion/exocytosis of interleukin-6 and tumor necrosis factor alpha from synoviocytes. (PMID:24373201)
• These results indicated that Uukuniemi virus relies on VAMP3 for penetration, providing an indication of added complexity in the trafficking of viruses through the endocytic network. (PMID:24850728)
• phosphatidylinositol 4-kinase IIalpha knockdown inhibited vesicle-associated membrane protein 3 trafficking to perinuclear membranes and impaired the rate of VAMP3-mediated recycling of the transferrin receptor (PMID:25002402)
• highlight the role that VAMP3 and VAMP7 play in selection of the pathways leading to generation of ultrastructurally different LC3 compartments (PMID:25046114)
• Liquid chromatography-MS/MS analysis showed that the HHV-6 gM/gN complex interacts with the v-SNARE protein, vesicle-associated membrane protein 3 (VAMP3). (PMID:25209806)
• The small GTPase Rab8 interacts with VAMP-3 to regulate the delivery of recycling T-cell receptors to the immune synapse. (PMID:26034069)
• RABGEF1 mediates recycling endosome fusion with GAS-containing autophagosome-like vacuoles through the STX6-VAMP3-VTI1B complex; SNAREs are involved in autophagosome formation in response to bacterial infection (PMID:27791468)
• The authors found that activation of dendritic cells by bacterial lipopolysaccharide leads to increased Forster resonance energy transfer-fluorescence of fluorescently labeled syntaxin 4 with VAMP3 specifically at the plasma membrane, indicating increased SNARE complex formation, whereas FRET with other tested SNAREs was unaltered. (PMID:28524818)
• Knockdown of VAMP3 and SNAP23 reduces endothelial secretion of miR-126-3p and miR-200a-3p, as well as the proliferation, migration, and suppression of contractile markers in smooth muscle cells caused by vascular endothelial cell-coculture. (PMID:28716920)
• this study demonstrates the role of VAMP3 in mediating cytokine secretion related to atopic dermatitis (PMID:31128202)
• Circ_0002984 induces proliferation, migration and inflammation response of VSMCs induced by ox-LDL through miR-326-3p/VAMP3 axis in atherosclerosis. (PMID:34169652)
• CCAAT enhancer binding protein delta activates vesicle associated membrane protein 3 transcription to enhance chemoresistance and extracellular PD-L1 expression in triple-negative breast cancer. (PMID:38627816)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	vamp3	ENSDARG00000070161
mus_musculus	Vamp3	ENSMUSG00000028955
rattus_norvegicus	Vamp3	ENSRNOG00000030055
drosophila_melanogaster	Syb	FBGN0003660
caenorhabditis_elegans		WBGENE00004898
caenorhabditis_elegans		WBGENE00004899
caenorhabditis_elegans		WBGENE00014084
caenorhabditis_elegans		WBGENE00044062

Paralogs (10): SEC22C (ENSG00000093183), YKT6 (ENSG00000106636), VAMP4 (ENSG00000117533), VAMP8 (ENSG00000118640), SEC22A (ENSG00000121542), VAMP7 (ENSG00000124333), VAMP1 (ENSG00000139190), VAMP5 (ENSG00000168899), VAMP2 (ENSG00000220205), SEC22B (ENSG00000265808)

Protein

Protein identifiers

Vesicle-associated membrane protein 3 — Q15836 (reviewed: Q15836)

Alternative names: Cellubrevin, Synaptobrevin-3

All UniProt accessions (3): K7EKX0, Q15836, Q6FGG2

UniProt curated annotations — full annotation on UniProt →

Function. SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network.

Subunit / interactions. Interacts with POPDC1 (via the C-terminus cytoplasmic tail). Interacts with BCAP31; involved in VAMP3 export from the endoplasmic reticulum. Interacts with BAIAP3; this interaction is increased in the presence of calcium. Interacts with PICALM.

Subcellular location. Early endosome membrane. Recycling endosome membrane. Synapse. Synaptosome.

Post-translational modifications. Ubiquitinated by RNF167 at Lys-66, Lys-68 and Lys-77, regulating the recycling endosome pathway. (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type B (BoNT/B, botB) which hydrolyzes the 59-Gln-|-Phe-60 bond and probably inhibits neurotransmitter release. (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type D (BoNT/D, botD) which hydrolyzes the 42-Lys-|-Leu-43 bond and probably inhibits neurotransmitter release. Note that humans are not known to be infected by C.botulinum type D. (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type F (BoNT/F, botF) which hydrolyzes the 41-Gln-|-Lys-42 bond and probably inhibits neurotransmitter release.

Similarity. Belongs to the synaptobrevin family.

RefSeq proteins (1): NP_004772* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00957

UniProt features (16 total): cross-link 3, site 3, mutagenesis site 2, topological domain 2, initiator methionine 1, chain 1, sequence conflict 1, transmembrane region 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15836-F1	91.56	0.80

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 (3): 41–42 ((microbial infection) cleavage; by c.botulinum neurotoxin type f (bont/f, botf)); 42–43 ((microbial infection) cleavage; by c.botulinum neurotoxin type d (bont/d, botd)); 58–59 ((microbial infection) cleavage; by c.botulinum neurotoxin type b (bont/b, botb))

Post-translational modifications (4): 66, 68, 77, 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
66–68	abolished ubiquitination by rnf167; when associated with r-77.
77	abolished ubiquitination by rnf167; when associated with 66-r–r-68.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013407	RHOH GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9035034	RHOF GTPase cycle

MSigDB gene sets: 400 (showing top): RNGTGGGC_UNKNOWN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_MEMBRANE_FUSION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE

GO Biological Process (16): positive regulation of receptor recycling (GO:0001921), exocytosis (GO:0006887), obsolete vesicle docking involved in exocytosis (GO:0006904), vesicle fusion (GO:0006906), vesicle-mediated transport (GO:0016192), calcium-ion regulated exocytosis (GO:0017156), substrate adhesion-dependent cell spreading (GO:0034446), SNARE complex assembly (GO:0035493), retrograde transport, endosome to Golgi (GO:0042147), Golgi to plasma membrane protein transport (GO:0043001), membrane fusion (GO:0061025), protein-containing complex assembly (GO:0065003), cellular response to type II interferon (GO:0071346), negative regulation of secretion by cell (GO:1903531), protein transport (GO:0015031), establishment of localization in cell (GO:0051649)

GO Molecular Function (3): SNAP receptor activity (GO:0005484), syntaxin-1 binding (GO:0017075), protein binding (GO:0005515)

GO Cellular Component (23): cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), transport vesicle (GO:0030133), clathrin-coated vesicle (GO:0030136), secretory granule (GO:0030141), clathrin-coated endocytic vesicle membrane (GO:0030669), phagocytic vesicle membrane (GO:0030670), SNARE complex (GO:0031201), early endosome membrane (GO:0031901), trans-Golgi network membrane (GO:0032588), neuron projection (GO:0043005), intracellular membrane-bounded organelle (GO:0043231), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), endosome (GO:0005768), early endosome (GO:0005769), endomembrane system (GO:0012505), cytoplasmic vesicle (GO:0031410), phagocytic vesicle (GO:0045335)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	13
Antigen processing-Cross presentation	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
endomembrane system	3
vesicle-mediated transport	2
secretion by cell	2
transport	2
cytoplasmic vesicle	2
endocytic vesicle membrane	2
endosome membrane	2
endosome	2
receptor recycling	1
regulation of receptor recycling	1
positive regulation of macromolecule metabolic process	1
positive regulation of signaling	1
vesicle fusion to plasma membrane	1
vesicle organization	1
organelle membrane fusion	1
cellular process	1
regulated exocytosis	1
cell-substrate adhesion	1
vesicle fusion	1
protein-containing complex assembly	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
Golgi to plasma membrane transport	1
protein transport	1
establishment of protein localization to plasma membrane	1
protein localization to plasma membrane	1
membrane organization	1
cellular component assembly	1
protein-containing complex organization	1
response to type II interferon	1
cellular response to cytokine stimulus	1
negative regulation of cellular process	1
negative regulation of secretion	1
regulation of secretion by cell	1
intracellular protein localization	1
establishment of protein localization	1
establishment of localization	1

Protein interactions and networks

STRING

2486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VAMP3	SNAP23	O00161	999
VAMP3	STX4	Q12846	999
VAMP3	STX6	O43752	996
VAMP3	STX16	O14662	983
VAMP3	VAMP7	P51809	980
VAMP3	STX10	O60499	977
VAMP3	VTI1A	Q96AJ9	977
VAMP3	STX1B	P61266	961
VAMP3	STX3	Q13277	961
VAMP3	STX2	P32856	894
VAMP3	SNAP25	P13795	873
VAMP3	STX1A	Q16623	871
VAMP3	VTI1B	Q9UEU0	842
VAMP3	CD9	P21926	794
VAMP3	STX7	O15400	787

IntAct

427 interactions, top by confidence:

A	B	Type	Score
STX4	VAMP3	psi-mi:“MI:0915”(physical association)	0.880
VAMP3	STX4	psi-mi:“MI:0915”(physical association)	0.880
SNAP29	VAMP3	psi-mi:“MI:0915”(physical association)	0.740
VAMP3	SNAP23	psi-mi:“MI:0915”(physical association)	0.670
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
EIF2B2	SLC27A2	psi-mi:“MI:0914”(association)	0.640
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
BCL2L13	VAMP3	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	BCL2L13	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	PTGES	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	TMX2	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	STX1A	psi-mi:“MI:0915”(physical association)	0.560
STX2	VAMP3	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	AHNAK2	psi-mi:“MI:0915”(physical association)	0.560
	VAMP3	psi-mi:“MI:0915”(physical association)	0.560
BIK	VAMP3	psi-mi:“MI:0915”(physical association)	0.560
BSCL2	VAMP3	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	GORAB	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	TMEM35A	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	RMDN3	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	CIAO2A	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	FAM209A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (494): VAMP3 (Two-hybrid), BCL2L13 (Two-hybrid), VAMP3 (Affinity Capture-MS), STX6 (Affinity Capture-Western), STX7 (Affinity Capture-Western), STX8 (Affinity Capture-Western), VAMP3 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS), VAMP3 (Affinity Capture-MS)

ESM2 similar proteins: O02495, O15155, O23429, O35623, O94651, O95183, P13701, P18489, P23763, P32867, P34351, P35589, P47192, P47193, P47194, P63024, P63025, P63026, P63027, P63044, P63045, P78768, P93654, Q04338, Q09730, Q0V7N0, Q15836, Q20574, Q27236, Q2KJD2, Q4R8T0, Q54GB3, Q5RBX2, Q60WU2, Q62442, Q62896, Q63666, Q6TMJ9, Q7XIE2, Q8VXX9

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

5 interactions.

A	Effect	B	Mechanism
VAMP3	“form complex”	“LE-TGN SNARE”	binding
RNF167	“down-regulates quantity by destabilization”	VAMP3	ubiquitination
BVES	“up-regulates activity”	VAMP3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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	5	16.2×	1e-03
trans-Golgi Network Vesicle Budding	5	15.9×	1e-03
Retrograde transport at the Trans-Golgi-Network	5	13.7×	2e-03
Intra-Golgi and retrograde Golgi-to-ER traffic	8	10.5×	1e-04
Membrane Trafficking	15	7.0×	1e-06
Vesicle-mediated transport	15	6.5×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	10	61.3×	2e-13
vesicle fusion	8	38.5×	7e-09
membrane fusion	6	30.0×	5e-06
exocytosis	12	14.6×	7e-09
retrograde transport, endosome to Golgi	7	11.5×	3e-04
endoplasmic reticulum to Golgi vesicle-mediated transport	7	7.6×	3e-03
intracellular protein transport	14	7.3×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

17 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	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

563 predictions. Top by Δscore:

Variant	Effect	Δscore
1:7771384:AT:A	donor_gain	1.0000
1:7771384:ATGT:A	donor_loss	1.0000
1:7771385:TGTG:T	donor_loss	1.0000
1:7771386:G:GG	donor_gain	1.0000
1:7771386:GT:G	donor_loss	1.0000
1:7778112:TTACA:T	acceptor_loss	1.0000
1:7778113:TACA:T	acceptor_loss	1.0000
1:7778114:ACAG:A	acceptor_loss	1.0000
1:7778115:CA:C	acceptor_loss	1.0000
1:7778116:A:AG	acceptor_gain	1.0000
1:7778117:G:GG	acceptor_gain	1.0000
1:7778117:GAT:G	acceptor_gain	1.0000
1:7778117:GATGT:G	acceptor_gain	1.0000
1:7779624:A:AG	acceptor_gain	1.0000
1:7779624:AGTGT:A	acceptor_gain	1.0000
1:7779625:G:GG	acceptor_gain	1.0000
1:7779625:GT:G	acceptor_gain	1.0000
1:7779625:GTGTG:G	acceptor_gain	1.0000
1:7771382:AAAT:A	donor_gain	0.9900
1:7771383:AAT:A	donor_gain	0.9900
1:7771388:GAGT:G	donor_loss	0.9900
1:7777156:CTAG:C	acceptor_loss	0.9900
1:7777157:TAGG:T	acceptor_loss	0.9900
1:7777317:AGGTA:A	donor_loss	0.9900
1:7777318:GGTA:G	donor_loss	0.9900
1:7777319:G:GC	donor_loss	0.9900
1:7777320:T:A	donor_loss	0.9900
1:7778111:GTTAC:G	acceptor_loss	0.9900
1:7778167:TCGGT:T	donor_loss	0.9900
1:7778168:CGG:C	donor_loss	0.9900

AlphaMissense

653 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:7777265:T:C	F60L	1.000
1:7777267:T:A	F60L	1.000
1:7777267:T:G	F60L	1.000
1:7777215:T:C	L43P	0.999
1:7777233:G:C	R49P	0.999
1:7777235:G:C	A50P	0.999
1:7777241:G:C	A52P	0.999
1:7777245:T:C	L53P	0.999
1:7777266:T:C	F60S	0.999
1:7777266:T:G	F60C	0.999
1:7777277:G:C	A64P	0.999
1:7777176:G:C	R30P	0.998
1:7777183:C:A	N32K	0.998
1:7777183:C:G	N32K	0.998
1:7777197:T:C	L37P	0.998
1:7777224:T:C	L46S	0.998
1:7777250:G:C	A55P	0.998
1:7777256:G:C	A57P	0.998
1:7777257:C:A	A57D	0.998
1:7777173:T:A	M29K	0.997
1:7777203:G:T	R39I	0.997
1:7777204:A:C	R39S	0.997
1:7777204:A:T	R39S	0.997
1:7777206:A:T	D40V	0.997
1:7777215:T:A	L43H	0.997
1:7777160:G:C	V25L	0.996
1:7777160:G:T	V25L	0.996
1:7777173:T:G	M29R	0.996
1:7777182:A:T	N32I	0.996
1:7777259:T:C	S58P	0.996

dbSNP variants (sampled 300 via entrez): RS1000046262 (1:7770773 G>A,C), RS1000222007 (1:7771767 T>G), RS1000310433 (1:7776034 G>T), RS1000508107 (1:7770769 A>G), RS1000723448 (1:7780935 A>G), RS1000883227 (1:7781874 T>C), RS1000947946 (1:7776638 C>A), RS1000964394 (1:7770297 C>A), RS1001008223 (1:7776339 G>C), RS1001529450 (1:7771518 T>A), RS1001581775 (1:7777676 AG>A), RS1001621339 (1:7779061 C>A,G,T), RS1001633188 (1:7773099 A>G), RS1001716287 (1:7771706 G>T), RS1002667000 (1:7780109 C>G)

Disease associations

OMIM: gene MIM:603657 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000879_31	Crohn’s disease	7.000000e-09
GCST001588_5	Periodontal microbiota	5.000000e-06
GCST003429_37	Morning vs. evening chronotype	2.000000e-08
GCST004131_79	Inflammatory bowel disease	1.000000e-12
GCST004132_92	Crohn’s disease	3.000000e-06
GCST004133_62	Ulcerative colitis	4.000000e-09
GCST90093091_1	DHEAS levels	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007001	dehydroepiandrosterone sulphate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases methylation	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	increases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sodium arsenite	increases expression	1
coumarin	affects phosphorylation	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Etoposide	affects expression	1
Formaldehyde	increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Sarin	decreases expression	1
Smoke	decreases expression	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	affects expression	1

Clinical trials (associated diseases)

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