VAMP7

Summary

VAMP7 (vesicle associated membrane protein 7, HGNC:11486) is a protein-coding gene on chromosome Xq28 and Yq12, encoding Vesicle-associated membrane protein 7 (P51809). Involved in the targeting and/or fusion of transport vesicles to their target membrane during transport of proteins from the early endosome to the lysosome.

This gene encodes a transmembrane protein that is a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family. The encoded protein localizes to late endosomes and lysosomes and is involved in the fusion of transport vesicles to their target membranes. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 6845 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 129 total
• Phenotypes (HPO): 43
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005638

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11486
Approved symbol	VAMP7
Name	vesicle associated membrane protein 7
Location	Xq28 and Yq12
Locus type	gene with protein product
Status	Approved
Aliases	VAMP-7, TI-VAMP
Ensembl gene	ENSG00000124333
Ensembl biotype	protein_coding
OMIM	300053
Entrez	6845

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000262640, ENST00000286448, ENST00000460621, ENST00000463317, ENST00000479687, ENST00000488344, ENST00000895988, ENST00000895989, ENST00000895990, ENST00000936172, ENST00000936173, ENST00000942503, ENST00000942504, ENST00000942505, ENST00000942506

RefSeq mRNA: 3 — MANE Select: NM_005638 NM_001145149, NM_001185183, NM_005638

CCDS: CCDS14770, CCDS48199, CCDS55548

Canonical transcript exons

ENST00000286448 — 8 exons

Exon	Start	End
ENSE00001380487	155881345	155881448
ENSE00002096759	155889458	155889612
ENSE00003469069	155898112	155898249
ENSE00003506587	155919813	155919880
ENSE00003525378	155900497	155900587
ENSE00003552457	155939701	155939793
ENSE00003563079	155895623	155895680
ENSE00003571718	155941883	155943769

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.28.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.28	gold quality
oocyte	CL:0000023	99.08	gold quality
monocyte	CL:0000576	96.06	gold quality
mononuclear cell	CL:0000842	95.98	gold quality
endothelial cell	CL:0000115	95.68	gold quality
leukocyte	CL:0000738	95.67	gold quality
visceral pleura	UBERON:0002401	94.97	gold quality
pleura	UBERON:0000977	94.73	gold quality
parietal pleura	UBERON:0002400	94.73	gold quality
esophagus squamous epithelium	UBERON:0006920	94.51	gold quality
renal glomerulus	UBERON:0000074	94.11	gold quality
trabecular bone tissue	UBERON:0002483	93.86	gold quality
nephron tubule	UBERON:0001231	93.83	gold quality
metanephric glomerulus	UBERON:0004736	93.80	gold quality
tibia	UBERON:0000979	93.74	gold quality
skin of hip	UBERON:0001554	93.62	gold quality
upper leg skin	UBERON:0004262	93.61	gold quality
choroid plexus epithelium	UBERON:0003911	93.50	gold quality
epithelium of esophagus	UBERON:0001976	93.43	gold quality
bone marrow	UBERON:0002371	93.34	gold quality
squamous epithelium	UBERON:0006914	93.07	gold quality
parotid gland	UBERON:0001831	92.94	gold quality
calcaneal tendon	UBERON:0003701	92.94	gold quality
blood vessel layer	UBERON:0004797	92.94	gold quality
palpebral conjunctiva	UBERON:0001812	92.93	gold quality
jejunal mucosa	UBERON:0000399	92.84	gold quality
kidney epithelium	UBERON:0004819	92.73	gold quality
pons	UBERON:0000988	92.72	gold quality
placenta	UBERON:0001987	92.66	gold quality
cranial nerve II	UBERON:0000941	92.59	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, MBD2, NR1I2, ZNF143

miRNA regulators (miRDB)

120 targeting VAMP7, 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-3646	100.00	73.56	5283
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-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6715A-3P	99.83	68.05	1473

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• A G–>C transversion in a regulatory region was found to be associated with bipolar affective disorder. (PMID:11840509)
• In ICF (immunodeficiency, centromeric instability, facial abnormalities) syndrome SYBL1 escapes from silencing and this correlates with altered patterns of histone methylation and acetylation. (PMID:12444103)
• results reported here clarify that a Staf-zinc finger family factor is the major nuclear protein bound to the synaptobrevin-like 1 (SYBL1) promoter region and is responsible for its regulation in HeLa cells (PMID:14672948)
• VAMP-7 is involved in the constitutive exocytosis as a slow, minor v-SNARE, but not in lysosomal transport (PMID:16195891)
• Data show that the insensitivity of TI-VAMP to botulinum neurotoxin B relies on at least 12 amino acid changes versus VAMP-2, which are scattered along an interface of 22 amino acid residues in length. (PMID:16430921)
• Our results show that VAMP-7 is a crucial component of granzyme B release and target cell killing in the NK cell line YT-Indy. (PMID:18042464)
• 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)
• The participation of vesicle-associated membrane protein 7 as a partner of syntaxin 7 in VacA-induced vacuole formation is reported. (PMID:18362137)
• Collectively, these data point to a specific role of VAMP7 in delivering MT1-MMP to sites of matrix degradation, maintaining the functional machinery required for invasion. (PMID:18571410)
• Study demonstrates that the clathrin-mediated endocytosis of the SNARE VAMP7 is directly mediated by Hrb, a clathrin adaptor and ArfGAP. (PMID:18775314)
• HRB is involved in clathrin-dependent endocytosis and recruits TI-VAMP in this process (PMID:18819912)
• The present results suggest that a SNARE complex containing VAMP7 and Vti1a defines a novel traffic pathway to the cell surface in both neuronal and non-neuronal cells. (PMID:19138172)
• show that TI-VAMP interacts with the Vps9 domain and ankyrin-repeat-containing protein Varp, a guanine nucleotide exchange factor of the small GTPase Rab21, through a specific domain herein called the interacting domain. (PMID:19745841)
• TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. (PMID:19781582)
• Results highlight the role of TI-VAMP in the secretory pathway of a tetraspanin, and support a model in which CD82 allows EGFR entry in microdomains that control its clathrin-dependent endocytosis and signaling. (PMID:20144992)
• SNARE VAMP7/TI-VAMP adopts a closed conformation (PMID:20378544)
• Alternative splicing of SYBL1 by exon skipping events results in the production of a number of VAMP7 isoforms. (PMID:21609427)
• VAMP7 is involved in many fusion processes and thus plays a more general function in NK-cell activity than VAMP4. (PMID:21805468)
• The endosomal trafficking and recycling of MT1-MMP was found to be dependent upon Rab7 and VAMP7, and blocking the function of these proteins reduced cell migration and invasion. (PMID:22002060)
• Downregulation of VAMP7 expression inhibited the fusion of ATP-storing vesicles and ATP-mediated calcium wave propagation. (PMID:22188132)
• Behavioral characterization studies indicate that deletion of Vamp7 exon 7 is associated with a role for VAMP7 in higher brain functions. (PMID:22323709)
• These studies identify a new alpha-granule subtype expressing VAMP-7 that moves to the periphery during spreading, supporting the premise that alpha-granules are heterogeneous and demonstrating that granule exocytosis is required for platelet spreading. (PMID:22589474)
• In a mammalian tumor cell line a subset of VAMP7 (V-SNARE)-positive vacuoles colocalize with LC3 at the cell periphery (focal adhesions) upon starvation. (PMID:22951367)
• VAMP7-SNARE motif is trapped between Varp and the VAMP7 longin domain, and hence Varp kinetically inhibits the ability of VAMP7 to form SNARE complexes (PMID:23104059)
• Overexpression of Vamp7 inhibited the heterotypic fusion with lysosomes and the homotypic fusion between individual Coxiella phagosomes and replicative vacuoles. (PMID:23217169)
• hVps41 and VAMP7 are specifically involved in the fusion of trans-Golgi network-derived lysosome-associated membrane protein carriers with late endosomes. (PMID:23322049)
• Activation of TI-VAMP-mediated exocytosis thus relies on tyrosine phosphorylation. (PMID:23471971)
• CALM is able to sort VAMP4 and VAMP7, even though they have sorting signals for other clathrin adaptors. (PMID:23741335)
• Increased level of SNAP23-Syntaxin4-VAMP7 interaction correlates with decreased Syntaxin4 phosphorylation and trafficking of MT1-MMP to invadopodia during cellular invasion. (PMID:24807903)
• increased gene dosage of VAMP7, and thus higher expression levels of its protein product, enhances estrogen receptor action in male genitourinary tissues (PMID:24880616)
• highlight the role that VAMP3 and VAMP7 play in selection of the pathways leading to generation of ultrastructurally different LC3 compartments (PMID:25046114)
• VAMP-7 participates in both platelet granule secretion and spreading and suggest a mechanism whereby VAMP-7 links granule exocytosis with actin reorganization. (PMID:25999457)
• The pseudoautosomal region of human X and Y chromosome encoded VAMP7 protein was predicted to interact with at least 22 proteins encoded on the somatic chromosomes. (PMID:26279084)
• GLUT5 required an interaction cascade of Rab11, Myo5B, Slp4a, Munc18-2, and Vamp7 with Stx3. (PMID:26553929)
• DIPK2A promotes STX17- and VAMP7-mediated autophagosome-lysosome fusion by binding to VAMP7B. (PMID:31251111)
• Cytotoxic Granule Exocytosis From Human Cytotoxic T Lymphocytes Is Mediated by VAMP7. (PMID:31447853)
• Gene Copy Number Quantification of SHOX, VAMP7, and SRY for the Detection of Sex Chromosome Aneuploidies in Neonates. (PMID:32423256)
• A case series of infants with increased VAMP7 gene dosage at birth and virilization defects. (PMID:32622737)
• Role of VAMP7-Dependent Secretion of Reticulon 3 in Neurite Growth. (PMID:33357422)
• A BLOC-1-AP-3 super-complex sorts a cis-SNARE complex into endosome-derived tubular transport carriers. (PMID:33886957)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sybl1	ENSDARG00000030775
rattus_norvegicus	Vamp7	ENSRNOG00000008372
drosophila_melanogaster	Vamp7	FBGN0266186
caenorhabditis_elegans		WBGENE00004899
caenorhabditis_elegans		WBGENE00014084
caenorhabditis_elegans		WBGENE00044062

Paralogs (10): VAMP3 (ENSG00000049245), SEC22C (ENSG00000093183), YKT6 (ENSG00000106636), VAMP4 (ENSG00000117533), VAMP8 (ENSG00000118640), SEC22A (ENSG00000121542), VAMP1 (ENSG00000139190), VAMP5 (ENSG00000168899), VAMP2 (ENSG00000220205), SEC22B (ENSG00000265808)

Protein

Protein identifiers

Vesicle-associated membrane protein 7 — P51809 (reviewed: P51809)

Alternative names: Synaptobrevin-like protein 1, Tetanus-insensitive VAMP

All UniProt accessions (2): E5RH06, P51809

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the targeting and/or fusion of transport vesicles to their target membrane during transport of proteins from the early endosome to the lysosome. Required for heterotypic fusion of late endosomes with lysosomes and homotypic lysosomal fusion. Required for calcium regulated lysosomal exocytosis. Involved in the export of chylomicrons from the endoplasmic reticulum to the cis Golgi. Required for exocytosis of mediators during eosinophil and neutrophil degranulation, and target cell killing by natural killer cells. Required for focal exocytosis of late endocytic vesicles during phagosome formation.

Subunit / interactions. Component of the SNARE complex composed of STX4, SNAP23 and VAMP7 that binds SYT7 during lysosomal exocytosis. Component of the SNARE complex composed of STX7, STX8, VAMP7 and VTI1B that is required for heterotypic fusion of late endosomes with lysosomes. May interact with STX17. Interacts with PICALM. Interacts with RAB21.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle membrane. Golgi apparatus. trans-Golgi network membrane. Late endosome membrane. Lysosome membrane. Endoplasmic reticulum membrane. Phagosome membrane. Synapse. Synaptosome.

Tissue specificity. Detected in all tissues tested.

Miscellaneous. The gene coding for this protein is located in the pseudoautosomal region 2 (PAR2) of X and Y chromosomes. Loss-of-function mutant (antisense inhibition) displays impaired granzyme B release and target cell killing by natural killer cells.

Similarity. Belongs to the synaptobrevin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51809-1	1, Ti-VAMPa/VAMP7a	yes
P51809-2	2, Ti-VAMPb/VAMP7b
P51809-3	3, Ti-VAMPc/VAMP7c

RefSeq proteins (3): NP_001138621, NP_001172112, NP_005629* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001388	Synaptobrevin-like	Family
IPR010908	Longin_dom	Domain
IPR011012	Longin-like_dom_sf	Homologous_superfamily
IPR042855	V_SNARE_CC	Domain
IPR051097	Synaptobrevin-like_transport	Family

Pfam: PF00957, PF13774

UniProt features (24 total): strand 7, helix 4, modified residue 3, splice variant 2, topological domain 2, domain 2, initiator methionine 1, chain 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DMW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51809-F1	84.59	0.57

Functional residue map

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

Post-translational modifications (3): 2, 167, 168

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-432720	Lysosome Vesicle Biogenesis
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9020591	Interleukin-12 signaling

MSigDB gene sets: 369 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, SHEPARD_BMYB_MORPHOLINO_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_LYSOSOMAL_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCM_MSN, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GOBP_VESICLE_ORGANIZATION

GO Biological Process (12): exocytosis (GO:0006887), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), vesicle fusion (GO:0006906), phagocytosis, engulfment (GO:0006911), endosome to lysosome transport (GO:0008333), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), calcium-ion regulated exocytosis (GO:0017156), eosinophil degranulation (GO:0043308), neutrophil degranulation (GO:0043312), natural killer cell degranulation (GO:0043320), positive regulation of histamine secretion by mast cell (GO:1903595)

GO Molecular Function (3): SNARE binding (GO:0000149), SNAP receptor activity (GO:0005484), protein binding (GO:0005515)

GO Cellular Component (28): cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), membrane (GO:0016020), lamellipodium (GO:0030027), secretory granule (GO:0030141), transport vesicle membrane (GO:0030658), secretory granule membrane (GO:0030667), clathrin-coated endocytic vesicle membrane (GO:0030669), phagocytic vesicle membrane (GO:0030670), platelet alpha granule (GO:0031091), pseudopodium (GO:0031143), SNARE complex (GO:0031201), late endosome membrane (GO:0031902), azurophil granule membrane (GO:0035577), neuron projection (GO:0043005), synapse (GO:0045202), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), cytoplasmic vesicle (GO:0031410), plasma membrane bounded cell projection (GO:0120025)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Membrane Trafficking	2
trans-Golgi Network Vesicle Budding	2
Clathrin-mediated endocytosis	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle-mediated transport	3
leukocyte degranulation	3
plasma membrane bounded cell projection	3
cytoplasm	2
intercellular transport	2
transport	2
cellular anatomical structure	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
secretory granule	2
endocytic vesicle membrane	2
secretion by cell	1
vesicle fusion to plasma membrane	1
intracellular transport	1
Golgi vesicle transport	1
vesicle organization	1
organelle membrane fusion	1
phagocytosis	1
plasma membrane invagination	1
lysosomal transport	1
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
regulated exocytosis	1
eosinophil activation involved in immune response	1
eosinophil mediated immunity	1
neutrophil activation involved in immune response	1
neutrophil mediated immunity	1
natural killer cell activation involved in immune response	1
natural killer cell mediated cytotoxicity	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
protein binding	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1

Protein interactions and networks

STRING

2030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VAMP7	SNAP23	O00161	999
VAMP7	STX4	Q12846	999
VAMP7	STX7	O15400	997
VAMP7	SNAP29	O95721	996
VAMP7	STX17	P56962	995
VAMP7	VAMP8	Q9BV40	990
VAMP7	VTI1A	Q96AJ9	986
VAMP7	VTI1B	Q9UEU0	984
VAMP7	VAMP3	Q15836	980
VAMP7	STX8	Q9UNK0	978
VAMP7	SYT7	O43581	974
VAMP7	SNAP25	P13795	966
VAMP7	VAMP2	P19065	954
VAMP7	STX3	Q13277	953
VAMP7	BET1	O15155	952

IntAct

118 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
STX6	GOSR2	psi-mi:“MI:0914”(association)	0.670
STX3	SNAP23	psi-mi:“MI:0914”(association)	0.660
VAMP7	AGFG1	psi-mi:“MI:0915”(physical association)	0.640
AGFG1	VAMP7	psi-mi:“MI:0915”(physical association)	0.640
AGFG1	VAMP7	psi-mi:“MI:0407”(direct interaction)	0.640
VAMP7	AGFG1	psi-mi:“MI:0407”(direct interaction)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
VAMP7		psi-mi:“MI:0915”(physical association)	0.600
VAMP7		psi-mi:“MI:0403”(colocalization)	0.600
PIP4P2	NEDD4	psi-mi:“MI:0914”(association)	0.590
NAPA	NBAS	psi-mi:“MI:0914”(association)	0.530
ATP6V0A1	ATP6V1G1	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
STX12	FAM234B	psi-mi:“MI:0914”(association)	0.530
GINM1	ADCY9	psi-mi:“MI:0914”(association)	0.530
STX3	NBAS	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
VAMP7	STX7	psi-mi:“MI:0914”(association)	0.530

BioGRID (204): STX6 (Affinity Capture-Western), STX7 (Affinity Capture-Western), STX8 (Affinity Capture-Western), VAMP7 (Affinity Capture-MS), VAMP7 (Affinity Capture-MS), VAMP7 (Affinity Capture-MS), VAMP7 (Affinity Capture-MS), VAMP7 (Affinity Capture-MS), VAMP7 (Proximity Label-MS), VAMP7 (Affinity Capture-Western), VAMP7 (Affinity Capture-Western), VAMP7 (Affinity Capture-MS), VAMP7 (Affinity Capture-MS), VAMP7 (Affinity Capture-MS), VAMP7 (Affinity Capture-MS)

ESM2 similar proteins: A0JN39, A8WGF4, D2SW95, G3V7P1, O00232, O08547, O08595, O14662, O49377, O75396, P23514, P51809, P53618, P70280, Q0DJ99, Q0DJA0, Q0JNK5, Q17QI5, Q4KM74, Q53PC7, Q5R922, Q5RAI9, Q5RBI3, Q5RBW6, Q5RF94, Q5VQ78, Q5ZIA5, Q5ZJW4, Q5ZL74, Q66HV4, Q6H8D5, Q6H8D6, Q6NYH1, Q6P7L4, Q7QG73, Q7SXP0, Q8L828, Q94AU2, Q9C827, Q9CAA0

Diamond homologs: O23429, O48850, O49377, O70404, O70480, O75379, P31109, P33328, P47192, P51809, P70280, Q12255, Q17QI5, Q27236, Q32L97, Q3T0Y8, Q54GB3, Q5REQ5, Q5RF94, Q5ZL74, Q63666, Q6TMJ9, Q86AQ7, Q8VY69, Q92356, Q9BV40, Q9FMR5, Q9JHW5, Q9LFP1, Q9M376, Q9MAS5, Q9SIQ9, Q9W0C1, Q9WUF4, Q9ZTW3, O02495, P13701, P18489, P23763, P35589

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	VAMP7	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
Downstream signal transduction	5	22.9×	1e-04
Intra-Golgi traffic	5	15.6×	5e-04
Retrograde transport at the Trans-Golgi-Network	5	13.2×	9e-04
RHOQ GTPase cycle	6	13.1×	3e-04
RHOJ GTPase cycle	5	12.1×	1e-03
Intra-Golgi and retrograde Golgi-to-ER traffic	8	10.1×	1e-04
Golgi-to-ER retrograde transport	5	8.0×	3e-03
RAC3 GTPase cycle	5	7.2×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	6	42.2×	2e-06
vesicle fusion	7	38.6×	3e-07
membrane fusion	6	34.4×	4e-06
lysosomal lumen acidification	5	30.9×	6e-05
endocytic recycling	6	14.7×	3e-04
regulation of macroautophagy	5	13.6×	2e-03
exocytosis	8	11.1×	6e-05
Ras protein signal transduction	5	9.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1188 predictions. Top by Δscore:

Variant	Effect	Δscore
X:155881447:AGGTA:A	donor_loss	1.0000
X:155881448:GG:G	donor_loss	1.0000
X:155881449:G:C	donor_loss	1.0000
X:155881450:T:G	donor_loss	1.0000
X:155889452:T:TA	acceptor_gain	1.0000
X:155889454:ATAGA:A	acceptor_loss	1.0000
X:155889456:A:AC	acceptor_loss	1.0000
X:155889456:A:AG	acceptor_gain	1.0000
X:155889457:G:GA	acceptor_gain	1.0000
X:155889457:GA:G	acceptor_gain	1.0000
X:155889457:GACT:G	acceptor_gain	1.0000
X:155889566:GC:G	donor_gain	1.0000
X:155889567:C:G	donor_gain	1.0000
X:155889609:GCAA:G	donor_gain	1.0000
X:155889613:G:GG	donor_gain	1.0000
X:155898108:TCAG:T	acceptor_loss	1.0000
X:155898110:A:AG	acceptor_gain	1.0000
X:155898110:AG:A	acceptor_gain	1.0000
X:155898111:G:A	acceptor_loss	1.0000
X:155898111:G:GC	acceptor_gain	1.0000
X:155898111:GG:G	acceptor_gain	1.0000
X:155898111:GGA:G	acceptor_gain	1.0000
X:155898111:GGAT:G	acceptor_gain	1.0000
X:155898111:GGATT:G	acceptor_gain	1.0000
X:155898246:GCTG:G	donor_gain	1.0000
X:155898247:CTG:C	donor_loss	1.0000
X:155898248:TG:T	donor_loss	1.0000
X:155898249:GG:G	donor_loss	1.0000
X:155898252:A:C	donor_loss	1.0000
X:155898266:GA:G	donor_gain	1.0000

AlphaMissense

2892 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:57082186:T:C	C64R	0.999
Y:57082188:T:G	C64W	0.999
Y:57084683:T:C	F86L	0.999
Y:57084684:T:C	F86S	0.999
Y:57084685:C:A	F86L	0.999
Y:57084685:C:G	F86L	0.999
Y:57076009:T:A	V8D	0.998
Y:57076011:G:C	A9P	0.998
Y:57076012:C:A	A9D	0.998
Y:57076030:T:A	L15H	0.998
Y:57082184:T:C	L63P	0.998
Y:57082187:G:A	C64Y	0.998
Y:57084653:T:C	F76L	0.998
Y:57084655:T:A	F76L	0.998
Y:57084655:T:G	F76L	0.998
Y:57084663:T:C	L79P	0.998
Y:57084717:C:A	A97E	0.998
Y:57084728:G:C	A101P	0.998
Y:57084744:T:C	F106S	0.998
Y:57087081:T:C	L136P	0.998
Y:57087093:T:A	M140K	0.998
Y:57106341:G:C	A148P	0.998
Y:57106348:G:C	R150P	0.998
Y:57106369:T:C	L157S	0.998
Y:57106390:T:C	L164P	0.998
Y:57076030:T:C	L15P	0.997
Y:57076032:G:C	A16P	0.997
Y:57076033:C:A	A16D	0.997
Y:57076058:C:A	N24K	0.997
Y:57076058:C:G	N24K	0.997

dbSNP variants (sampled 300 via entrez): RS1000004843 (X:155896621 C>A,T), RS1000062989 (X:155933574 G>A), RS1000134512 (X:155933748 A>T), RS1000225382 (X:155909520 G>C), RS1000252100 (X:155913064 A>G,T), RS1000283310 (X:155912753 T>C), RS1000366016 (X:155938212 C>G), RS1000444807 (X:155896368 A>G), RS1000539845 (X:155930447 A>G), RS1000569856 (X:155891526 G>T), RS1000626464 (X:155918707 C>T), RS1000634782 (X:155884360 T>C,G), RS1000689863 (X:155924816 A>G), RS1000801275 (X:155918572 A>G), RS1000832124 (X:155902966 C>G)

Disease associations

OMIM: gene MIM:300053 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000030	Testicular gonadoblastoma
HP:0000045	Abnormal scrotum morphology
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000058	Abnormal labia morphology
HP:0000062	Ambiguous genitalia
HP:0000100	Nephrotic syndrome
HP:0000133	Gonadal dysgenesis
HP:0000142	Abnormal vagina morphology
HP:0000149	Ovarian gonadoblastoma
HP:0000150	Gonadoblastoma
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000812	Abnormal internal genitalia
HP:0000815	Hypergonadotropic hypogonadism
HP:0000823	Delayed puberty
HP:0000837	Increased circulating gonadotropin level
HP:0000846	Adrenal insufficiency
HP:0000868	Decreased fertility in females
HP:0000939	Osteoporosis
HP:0002215	Sparse axillary hair
HP:0002225	Sparse pubic hair
HP:0002667	Nephroblastoma
HP:0002750	Delayed skeletal maturation
HP:0003251	Male infertility
HP:0008187	Absence of secondary sex characteristics
HP:0008193	Primary gonadal insufficiency
HP:0008214	Decreased serum estradiol

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066305 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression, decreases reaction	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression	1
mercuric bromide	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Nickel	affects expression, decreases reaction	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	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
CHEMBL5652793	Binding	Binding affinity to human VAMP7 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

Clinical trials (associated diseases)

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