SNAP23

Summary

SNAP23 (synaptosome associated protein 23, HGNC:11131) is a protein-coding gene on chromosome 15q15.1-q15.2, encoding Synaptosomal-associated protein 23 (O00161). Essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion. It is a selective cancer dependency (DepMap: 65.7% of cell lines).

Specificity of vesicular transport is regulated, in part, by the interaction of a vesicle-associated membrane protein termed synaptobrevin/VAMP with a target compartment membrane protein termed syntaxin. These proteins, together with SNAP25 (synaptosome-associated protein of 25 kDa), form a complex which serves as a binding site for the general membrane fusion machinery. Synaptobrevin/VAMP and syntaxin are believed to be involved in vesicular transport in most, if not all cells, while SNAP25 is present almost exclusively in the brain, suggesting that a ubiquitously expressed homolog of SNAP25 exists to facilitate transport vesicle/target membrane fusion in other tissues. The protein encoded by this gene is structurally and functionally similar to SNAP25 and binds tightly to multiple syntaxins and synaptobrevins/VAMPs. It is an essential component of the high affinity receptor for the general membrane fusion machinery and is an important regulator of transport vesicle docking and fusion. Two alternative transcript variants encoding different protein isoforms have been described for this gene.

Source: NCBI Gene 8773 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 65.7% of screened cell lines
• MANE Select transcript: NM_003825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11131
Approved symbol	SNAP23
Name	synaptosome associated protein 23
Location	15q15.1-q15.2
Locus type	gene with protein product
Status	Approved
Aliases	SNAP23A, SNAP23B, HsT17016
Ensembl gene	ENSG00000092531
Ensembl biotype	protein_coding
OMIM	602534
Entrez	8773

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 27 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000249647, ENST00000349777, ENST00000397138, ENST00000561526, ENST00000563333, ENST00000563451, ENST00000563765, ENST00000563830, ENST00000563873, ENST00000564153, ENST00000566035, ENST00000566141, ENST00000566327, ENST00000567094, ENST00000568227, ENST00000568331, ENST00000568451, ENST00000568514, ENST00000568745, ENST00000568841, ENST00000568859, ENST00000626061, ENST00000627440, ENST00000873737, ENST00000873738, ENST00000873739, ENST00000873740, ENST00000873741, ENST00000873742, ENST00000873743, ENST00000873744, ENST00000926282, ENST00000960520, ENST00000960521, ENST00000960522, ENST00000960523, ENST00000960524

RefSeq mRNA: 2 — MANE Select: NM_003825 NM_003825, NM_130798

CCDS: CCDS10087, CCDS10088

Canonical transcript exons

ENST00000249647 — 8 exons

Exon	Start	End
ENSE00001921361	42495634	42495713
ENSE00001950216	42531413	42533058
ENSE00003473126	42512955	42512996
ENSE00003530990	42515237	42515354
ENSE00003547573	42511833	42511903
ENSE00003567479	42513399	42513447
ENSE00003635811	42529675	42529819
ENSE00003689744	42528262	42528420

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.3909 / max 710.7732, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146273	49.8684	1822
146272	0.3895	176
146271	0.1130	40
146270	0.0200	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.73	gold quality
mononuclear cell	CL:0000842	98.68	gold quality
leukocyte	CL:0000738	98.53	gold quality
jejunal mucosa	UBERON:0000399	98.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.66	gold quality
epithelium of nasopharynx	UBERON:0001951	97.58	gold quality
nasopharynx	UBERON:0001728	97.57	gold quality
colonic mucosa	UBERON:0000317	97.50	gold quality
colonic epithelium	UBERON:0000397	97.50	gold quality
lower lobe of lung	UBERON:0008949	97.45	gold quality
placenta	UBERON:0001987	97.41	gold quality
calcaneal tendon	UBERON:0003701	97.34	gold quality
blood	UBERON:0000178	97.20	gold quality
superficial temporal artery	UBERON:0001614	97.17	gold quality
trabecular bone tissue	UBERON:0002483	97.11	gold quality
vermiform appendix	UBERON:0001154	97.03	gold quality
seminal vesicle	UBERON:0000998	96.92	gold quality
parotid gland	UBERON:0001831	96.75	gold quality
tonsil	UBERON:0002372	96.70	gold quality
bone marrow cell	CL:0002092	96.68	gold quality
descending thoracic aorta	UBERON:0002345	96.65	gold quality
visceral pleura	UBERON:0002401	96.61	gold quality
lymph node	UBERON:0000029	96.57	gold quality
jejunum	UBERON:0002115	96.45	gold quality
caecum	UBERON:0001153	96.36	gold quality
palpebral conjunctiva	UBERON:0001812	96.36	gold quality
pleura	UBERON:0000977	96.31	gold quality
parietal pleura	UBERON:0002400	96.31	gold quality
rectum	UBERON:0001052	96.29	gold quality
thoracic aorta	UBERON:0001515	96.21	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	33.45
E-CURD-122	yes	21.05
E-HCAD-10	yes	16.08
E-HCAD-1	yes	5.26
E-MTAB-2983	no	1076.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting SNAP23, 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-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-5688	99.96	73.23	4504
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-551B-5P	99.96	71.28	3493

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 65.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• SNAP-23 and syntaxin-4 are expressed in human eosinophils and are likely candidates for association with VAMP-2 during docking, which is followed by exocytosis. (PMID:11842301)
• cleaved by calpain in activated platelets (PMID:12121992)
• CFTR-mediated chloride currents are inhibited by introducing excess SNAP-23 into HT29-Cl.19A epithelial cells. (PMID:12209004)
• A synaptosome-associated protein of 23 kDa(SNAP23), the ubiqitously expressed homologue of SNAP25, has been shown to interact directly with ubiquitous kinesin heavy chain (uKHC). (PMID:12475239)
• Palmitoylated peptides from the cysteine-rich domain of this protein cause membrane fusion depending on peptide length, position of cysteines, and extent of palmitoylation. (PMID:12551899)
• an examination of the homotetrameric structure of the N-terminal domain of this protein (PMID:12556468)
• studies show that synaptosomal-associated protein-23 is phosphorylated in platelets during cell activation through a protein kinase C-related mechanism at two or more sites (PMID:12930825)
• Because SNAP-23 plays a central role in SNAREs complex formation, it was chosen to examine possible functional implications of the SNARE system in plasma cell Ig secretion. (PMID:16272324)
• expression of SNAP-23 and syntaxin-2 on the extracellular surface of the platelet plasma membrane. (PMID:17485553)
• SNAP-23 is not essential for constitutive exocytosis of secreted alkaline phosphatase (PMID:17825825)
• The expression of the SNARE protein SNAP-25 and its cellular homologue SNAP-23, as well as syntaxin1 and VAMP (vesicle-associated membrane protein) in samples of normal parathyroid tissue, chief cell adenoma, and parathyroid carcinoma, was examined. (PMID:18457912)
• Overexpression of a dominant negative SNAP-23 mutant suppressed expression of P-selectin, CD40L, CD41, CD61, release from dense granules and platelet aggregation (PMID:18665925)
• the importance of SNAP23 in the trafficking of matrix metalloproteinases during degradation of extracellular matrix substrates and subsequent cellular invasion (PMID:19910495)
• SNAP23 and SNAP25 palmitoylation is regulated by DHHC palmitoyl transferases (PMID:20519516)
• Introduction of the SNARE domain of SNAP-23 into neutrophils as an HIV transactivator of transcription (TAT) fusion protein significantly inhibits exocytosis of neutrophil granule subsets without altering signal transduction pathway activation. (PMID:21642540)
• Data show that knockdown of SNAP-23 inhibited the production of virus. (PMID:21768361)
• STX-3 and SNAP-23 are crucial for the release of all chemokines in mature human mast cells (PMID:21981832)
• Results suggest that phagosomal SNAP-23 is one of the key players regulating the phagosomal environment in macrophages. (PMID:23087210)
• Data suggest SNAP23 and VAMP3 (vesicle-associated membrane protein 3) participate in interleukin-1beta-, interleukin-1 receptor-, calcium signaling-dependent secretion/exocytosis of interleukin-6 and tumor necrosis factor alpha from synoviocytes. (PMID:24373201)
• The association of Src, EGFR and beta1 integrin is dependent upon membrane traffic that is mediated by syntaxin13 (officially known as STX12) and SNAP23. (PMID:24496451)
• Increased level of SNAP23-Syntaxin4-VAMP7 interaction correlates with decreased Syntaxin4 phosphorylation and trafficking of MT1-MMP to invadopodia during cellular invasion. (PMID:24807903)
• these data suggest that SNAP23 is a key component of the endothelial SNARE machinery that mediates endothelial exocytosis. (PMID:26266817)
• Localization of SNAP23 was found in plasma membrane, lipid droplets and mitochondria of skeletal muscle. (PMID:26733245)
• Study showed that SNAP23 was recruited to the close sites of lipid droplet (LD) in HCV-infected cells, implying that SNAP23 was required for HCV-induced LD enlargement and, HCV production. (PMID:27550144)
• A novel regulatory mechanism for SNAP23-dependent mast cell activation of T. vaginalis-secreted LTB4 involving surface trafficking of BLT1. (PMID:27795355)
• Study identified SNAP23 as a novel oncogene in Ovarian Cancer (OC). It is over-expressed in OC and could promote the proliferation, migration and invasion of OC in vitro. (PMID:27855700)
• PKM2 promotes tumor cell exosome release via phosphorylating protein SNAP23. (PMID:28067230)
• 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)
• Rab5 is essential for FcepsilonRI-triggered association of the SNARE protein SNAP23 with the secretory granules. (PMID:29127297)
• Data suggest that acylation of SNAP23 (synaptosome associated protein 23) and STX11 (syntaxin-11) regulates exocytosis in platelets; maintaining acylation states of SNAP23 and STX11 is important for platelet function. (PMID:29352103)
• SNAP23 suppressed progression of cervical cancer and induced cell cycle G2/M arrest via upregulating p21(cip1) and downregulating CyclinB1 (PMID:29908998)
• Results show that SNAP23 is phosphorylated by HOTAIR promoting the release of exosome from hepatocellular carcinoma cells. (PMID:30943982)
• issue and biofluid enrichment analyses show broad representation of EVs from across the body without bias towards kidney or urine proteins. Among the proteins linked to neurological diseases, SNAP23 and calbindin were the most elevated in Parkinson’s disease with 86% prediction success for disease diagnosis in the discovery cohort and 76% prediction success in the replication cohort. (PMID:31229437)
• Reduction in SNAP-23 Alters Microfilament Organization in Myofibrobastic Hepatic Stellate Cells. (PMID:31757226)
• SNAP23 depletion enables more SNAP25/calcium channel excitosome formation to increase insulin exocytosis in type 2 diabetes. (PMID:32051343)
• IKKbeta activation promotes amphisome formation and extracellular vesicle secretion in tumor cells. (PMID:32949647)
• Pancreas-specific SNAP23 depletion prevents pancreatitis by attenuating pathological basolateral exocytosis and formation of trypsin-activating autolysosomes. (PMID:33213278)
• Let-7a regulates EV secretion and mitochondrial oxidative phosphorylation by targeting SNAP23 in colorectal cancer. (PMID:33446221)
• LINC00511 drives invasive behavior in hepatocellular carcinoma by regulating exosome secretion and invadopodia formation. (PMID:34088337)
• SNAP23-Mediated Perturbation of Cholesterol-Enriched Membrane Microdomain Promotes Extracellular Vesicle Production in Src-Activated Cancer Cells. (PMID:36184518)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	snap23.1	ENSDARG00000012874
danio_rerio	snap23.2	ENSDARG00000055252
mus_musculus	Snap23	ENSMUSG00000027287
rattus_norvegicus	Snap23	ENSRNOG00000050552

Paralogs (3): SNAP29 (ENSG00000099940), SNAP25 (ENSG00000132639), SNAP47 (ENSG00000143740)

Protein

Protein identifiers

Synaptosomal-associated protein 23 — O00161 (reviewed: O00161)

Alternative names: Vesicle-membrane fusion protein SNAP-23

All UniProt accessions (12): O00161, A8K287, H3BM38, H3BNE1, H3BNG6, H3BP15, H3BPJ0, H3BQY9, H3BR18, H3BR99, H3BU94, H3BV99

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion.

Subunit / interactions. Homotetramer (via coiled-coil domain), also forms heterotetramers with STX4 and VAMP3. Found in a complex with VAMP8 and STX1A. Found in a complex with VAMP8 and STX4 in pancreas. Interacts simultaneously with SNAPIN and SYN4. Interacts with STX1A. Interacts with STX12. Interacts tightly to multiple syntaxins and synaptobrevins/VAMPs. Interacts with ZDHHC13 (via ANK repeats). Interacts with ZDHHC17 (via ANK repeats).

Subcellular location. Cell membrane. Synapse. Synaptosome.

Tissue specificity. Ubiquitous. Highest levels where found in placenta.

Similarity. Belongs to the SNAP-25 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00161-1	SNAP-23a	yes
O00161-2	SNAP-23b

RefSeq proteins (2): NP_003816, NP_570710 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000727	T_SNARE_dom	Domain
IPR000928	SNAP-25_dom	Domain

Pfam: PF00835

UniProt features (22 total): modified residue 8, lipid moiety-binding region 6, domain 2, splice variant 2, chain 1, sequence conflict 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1NHL	X-RAY DIFFRACTION	2.3
3ZUS	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00161-F1	83.10	0.50

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 (14): 110, 161, 79, 80, 83, 85, 87, 112, 1, 5, 6, 20, 23, 34

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-6798695	Neutrophil degranulation
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9035034	RHOF GTPase cycle
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 277 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, CHUNG_BLISTER_CYTOTOXICITY_DN, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_VESICLE_TARGETING, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (8): histamine secretion by mast cell (GO:0002553), exocytosis (GO:0006887), post-Golgi vesicle-mediated transport (GO:0006892), obsolete vesicle targeting (GO:0006903), protein transport (GO:0015031), synaptic vesicle priming (GO:0016082), synaptic vesicle fusion to presynaptic active zone membrane (GO:0031629), membrane fusion (GO:0061025)

GO Molecular Function (3): SNAP receptor activity (GO:0005484), syntaxin binding (GO:0019905), protein binding (GO:0005515)

GO Cellular Component (19): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), cilium (GO:0005929), phagocytic vesicle membrane (GO:0030670), SNARE complex (GO:0031201), specific granule membrane (GO:0035579), specific granule (GO:0042581), azurophil granule (GO:0042582), neuron projection (GO:0043005), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), presynapse (GO:0098793), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
RHO GTPase cycle	8
Membrane Trafficking	2
Immune System	2
Antigen processing-Cross presentation	1
Innate Immune System	1
Class I MHC mediated antigen processing & presentation	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
exocytic process	2
vesicle fusion to plasma membrane	2
synaptic vesicle exocytosis	2
plasma membrane bounded cell projection	2
secretory granule membrane	2
secretory granule	2
histamine secretion involved in inflammatory response	1
mast cell degranulation	1
establishment of localization in cell	1
vesicle-mediated transport	1
secretion by cell	1
Golgi vesicle transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein-containing complex assembly	1
synaptic vesicle membrane organization	1
membrane organization	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
SNARE binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cell-cell junction	1
cell-substrate junction	1
intraciliary transport particle	1
membrane-bounded organelle	1
endocytic vesicle membrane	1
phagocytic vesicle	1
membrane protein complex	1
specific granule	1
primary lysosome	1
extracellular vesicle	1

Protein interactions and networks

STRING

2246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNAP23	VAMP3	Q15836	999
SNAP23	VAMP2	P19065	999
SNAP23	VAMP7	P51809	999
SNAP23	STX4	Q12846	999
SNAP23	STX3	Q13277	999
SNAP23	VAMP8	Q9BV40	999
SNAP23	STX2	P32856	995
SNAP23	STX11	O75558	989
SNAP23	STX1A	Q16623	971
SNAP23	STX6	O43752	951
SNAP23	SEC22B	O75396	944
SNAP23	VAMP1	P23763	932
SNAP23	STX19	Q8N4C7	930
SNAP23	SNAPIN	O95295	917
SNAP23	SNAP29	O95721	897

IntAct

145 interactions, top by confidence:

A	B	Type	Score
STX11	SNAP23	psi-mi:“MI:0915”(physical association)	0.900
SNAP23	STX11	psi-mi:“MI:0915”(physical association)	0.900
STX11	SNAP23	psi-mi:“MI:0914”(association)	0.900
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
NAPA	SNAP23	psi-mi:“MI:0914”(association)	0.780
SNAP23	NAPA	psi-mi:“MI:0915”(physical association)	0.780
NAPA	SNAP23	psi-mi:“MI:0915”(physical association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
VAMP3	SNAP23	psi-mi:“MI:0915”(physical association)	0.670
VAMP3	SNAP23	psi-mi:“MI:0914”(association)	0.670
SNAP23	STX3	psi-mi:“MI:0915”(physical association)	0.660
STX3	SNAP23	psi-mi:“MI:0914”(association)	0.660
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
SNAP23	NAPB	psi-mi:“MI:0915”(physical association)	0.560
NAPB	SNAP23	psi-mi:“MI:0915”(physical association)	0.560
SNAP23	STX1A	psi-mi:“MI:0915”(physical association)	0.550
STX1A	SNAP23	psi-mi:“MI:0915”(physical association)	0.550
SCGN	SNAP23	psi-mi:“MI:0914”(association)	0.550
SNAP23	SCGN	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (348): SNAP23 (Two-hybrid), SNAP23 (Two-hybrid), VAMP5 (Two-hybrid), NAPB (Two-hybrid), SNAP23 (Two-hybrid), SNAP23 (Affinity Capture-Western), SNAP23 (Affinity Capture-MS), SNAP23 (Affinity Capture-MS), SNAP23 (Affinity Capture-MS), SNAP23 (Affinity Capture-MS), SNAP23 (Affinity Capture-MS), SNAP23 (Affinity Capture-MS), SNAP23 (Affinity Capture-MS), ABI2 (Two-hybrid), ABI3 (Two-hybrid)

ESM2 similar proteins: O00161, O09044, O15400, O35526, O64791, O70257, O70377, O70439, O88384, O95721, P32851, P36975, P36976, P36977, P36978, P58200, P61264, P61265, P61266, P61267, P61268, P83351, P83528, Q0E1I7, Q0II86, Q16623, Q16932, Q2KIU0, Q3ZBT5, Q42374, Q5NVG5, Q5R4L2, Q5R5K4, Q5R602, Q5TZ66, Q6PC54, Q7XIE2, Q8VZU2, Q944A9, Q9ERB0

Diamond homologs: O00161, O09044, O70377, P36975, P36976, P36977, P36978, P60877, P60878, P60879, P60880, P60881, Q17QQ3, Q5NVG5, Q5R1X1, Q5TZ66, Q6PC54, O74786, P40357, Q59XP0, Q6BKU3, Q6C5G0, Q6CSD1, Q6FY22, Q752V4, P55820, Q9SD96, Q9S7P9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	SNAP23	phosphorylation
SNAP23	“form complex”	“STX11-SNAP23 SNARE complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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	24.0×	1e-04
Retrograde transport at the Trans-Golgi-Network	7	23.3×	7e-06
trans-Golgi Network Vesicle Budding	6	23.1×	2e-05
MAP2K and MAPK activation	5	21.6×	1e-04
Golgi Associated Vesicle Biogenesis	7	21.2×	7e-06
Signaling by RAF1 mutants	5	21.1×	1e-04
Intra-Golgi traffic	5	19.7×	2e-04
Signaling by moderate kinase activity BRAF mutants	5	19.2×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking	9	77.5×	3e-13
vesicle fusion	10	67.6×	8e-14
membrane fusion	5	35.1×	2e-05
exocytosis	13	22.2×	5e-12
autophagosome maturation	5	19.7×	3e-04
intracellular protein transport	15	10.9×	1e-09
protein transport	11	5.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1466 predictions. Top by Δscore:

Variant	Effect	Δscore
15:42512953:A:AG	acceptor_gain	1.0000
15:42512954:G:GA	acceptor_gain	1.0000
15:42513397:A:AG	acceptor_gain	1.0000
15:42513398:G:GA	acceptor_gain	1.0000
15:42513445:AGGGT:A	donor_loss	1.0000
15:42513446:GG:G	donor_gain	1.0000
15:42513447:GG:G	donor_gain	1.0000
15:42513448:G:GG	donor_gain	1.0000
15:42513448:GTA:G	donor_loss	1.0000
15:42513449:T:A	donor_loss	1.0000
15:42515235:A:AG	acceptor_gain	1.0000
15:42515236:G:GG	acceptor_gain	1.0000
15:42528229:T:TA	acceptor_gain	1.0000
15:42528243:A:AG	acceptor_gain	1.0000
15:42529669:T:TA	acceptor_gain	1.0000
15:42529673:A:AG	acceptor_gain	1.0000
15:42529674:G:GA	acceptor_gain	1.0000
15:42529674:GC:G	acceptor_gain	1.0000
15:42529674:GCAT:G	acceptor_gain	1.0000
15:42529674:GCATA:G	acceptor_gain	1.0000
15:42544020:AG:A	donor_gain	1.0000
15:42544021:G:C	donor_gain	1.0000
15:42544051:AT:A	donor_gain	1.0000
15:42544052:T:TA	donor_gain	1.0000
15:42545072:CATA:C	donor_loss	1.0000
15:42545075:ACCT:A	donor_loss	1.0000
15:42545076:C:G	donor_loss	1.0000
15:42545258:GATAT:G	acceptor_gain	1.0000
15:42545259:ATAT:A	acceptor_gain	1.0000
15:42545260:TAT:T	acceptor_gain	1.0000

AlphaMissense

1399 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:42529746:T:C	L166P	0.931
15:42531432:G:C	R197P	0.916
15:42531455:G:C	A205P	0.904
15:42529757:G:C	A170P	0.903
15:42512955:T:C	S20P	0.902
15:42529716:T:C	L156P	0.902
15:42513399:T:C	S34P	0.897
15:42512988:G:C	A31P	0.884
15:42531413:G:C	A191P	0.884
15:42515243:T:C	L52P	0.870
15:42512959:T:C	L21P	0.865
15:42531443:G:C	A201P	0.863
15:42529714:C:A	N155K	0.861
15:42529714:C:G	N155K	0.861
15:42512989:C:A	A31D	0.844
15:42529696:A:C	E149D	0.838
15:42529696:A:T	E149D	0.838
15:42515249:G:C	R54P	0.830
15:42529749:A:T	K167I	0.826
15:42529758:C:A	A170D	0.826
15:42529695:A:T	E149V	0.814
15:42513443:A:C	Q48H	0.803
15:42513443:A:T	Q48H	0.803
15:42528272:T:C	F93L	0.795
15:42528274:T:A	F93L	0.795
15:42528274:T:G	F93L	0.795
15:42513408:G:C	A37P	0.791
15:42512968:C:A	T24K	0.790
15:42531431:C:A	R197S	0.765
15:42515315:T:C	L76P	0.760

dbSNP variants (sampled 300 via entrez): RS1000021467 (15:42502725 G>A), RS1000063744 (15:42493242 T>C), RS1000123406 (15:42500000 C>G), RS1000221779 (15:42531630 T>C), RS1000327909 (15:42523497 G>A), RS1000371997 (15:42524831 C>T), RS1000447761 (15:42516969 G>C), RS1000487969 (15:42524487 T>C), RS1000499677 (15:42533038 C>G,T), RS1000500553 (15:42503150 A>C), RS1000529008 (15:42497789 C>T), RS1000553443 (15:42533433 C>T), RS1000685219 (15:42493506 G>A), RS1000829092 (15:42525949 C>G,T), RS1000878231 (15:42520001 T>C,G)

Disease associations

OMIM: gene MIM:602534 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008103_17	Bipolar disorder	9.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066300 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.41	Kd	386.1	nM	CHEMBL5653589
6.38	ED50	416.1	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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	2149450: Binding affinity to human SNAP23 incubated for 45 mins by Kinobead based pull down assay	kd	0.3861	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	affects phosphorylation	1
selenomethylselenocysteine	decreases expression	1
methylmercuric chloride	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	affects expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
U 0126	affects expression, affects reaction	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	increases activity, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	decreases expression	1
Succimer	affects cotreatment, increases expression	1
Endosulfan	decreases expression	1
Formaldehyde	decreases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases 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
CHEMBL5652492	Binding	Binding affinity to human SNAP23 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

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1RV	HyCyte MIA PaCa-2 KO-hSNAP23	Cancer cell line	Male
CVCL_TP76	HAP1 SNAP23 (-) 1	Cancer cell line	Male
CVCL_TP77	HAP1 SNAP23 (-) 2	Cancer cell line	Male
CVCL_TP78	HAP1 SNAP23 (-) 3	Cancer cell line	Male
CVCL_TP79	HAP1 SNAP23 (-) 4	Cancer cell line	Male
CVCL_TP80	HAP1 SNAP23 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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