STX17

Summary

STX17 (syntaxin 17, HGNC:11432) is a protein-coding gene on chromosome 9q31.1, encoding Syntaxin-17 (P56962). SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes.

Enables SNAP receptor activity; SNARE binding activity; and protein phosphatase binding activity. Involved in several processes, including autophagosome membrane docking; endoplasmic reticulum to Golgi vesicle-mediated transport; and endoplasmic reticulum-Golgi intermediate compartment organization. Acts upstream of or within protein localization to phagophore assembly site. Located in several cellular components, including autophagosome membrane; endoplasmic reticulum-Golgi intermediate compartment; and mitochondria-associated endoplasmic reticulum membrane contact site. Part of SNARE complex.

Source: NCBI Gene 55014 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_017919

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11432
Approved symbol	STX17
Name	syntaxin 17
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20651
Ensembl gene	ENSG00000136874
Ensembl biotype	protein_coding
OMIM	604204
Entrez	55014

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000259400, ENST00000524405, ENST00000525342, ENST00000525579, ENST00000525640, ENST00000525847, ENST00000526607, ENST00000529340, ENST00000529385, ENST00000531035, ENST00000533696, ENST00000534052, ENST00000861129, ENST00000861130, ENST00000861131, ENST00000861132, ENST00000928328, ENST00000928329, ENST00000958301, ENST00000958302

RefSeq mRNA: 1 — MANE Select: NM_017919 NM_017919

CCDS: CCDS6745

Canonical transcript exons

ENST00000259400 — 8 exons

Exon	Start	End
ENSE00001022894	99968434	99974534
ENSE00002148473	99906654	99906706
ENSE00003471471	99928778	99928843
ENSE00003487881	99967653	99967739
ENSE00003535769	99960105	99960155
ENSE00003627714	99951060	99951285
ENSE00003668817	99959917	99960032
ENSE00003796095	99915178	99915362

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 94.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.2355 / max 215.3042, expressed in 1793 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97702	18.2355	1793

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	94.66	gold quality
secondary oocyte	CL:0000655	94.08	gold quality
calcaneal tendon	UBERON:0003701	92.79	gold quality
adrenal tissue	UBERON:0018303	92.09	gold quality
pylorus	UBERON:0001166	90.66	gold quality
skin of hip	UBERON:0001554	90.34	gold quality
corpus epididymis	UBERON:0004359	89.82	gold quality
caput epididymis	UBERON:0004358	89.79	gold quality
esophagus squamous epithelium	UBERON:0006920	88.95	gold quality
oocyte	CL:0000023	88.91	gold quality
cauda epididymis	UBERON:0004360	88.83	gold quality
trabecular bone tissue	UBERON:0002483	88.79	gold quality
tendon	UBERON:0000043	88.77	gold quality
cardia of stomach	UBERON:0001162	88.72	gold quality
mammalian vulva	UBERON:0000997	88.24	gold quality
upper leg skin	UBERON:0004262	87.92	gold quality
superficial temporal artery	UBERON:0001614	87.63	gold quality
oral cavity	UBERON:0000167	87.62	gold quality
pancreatic ductal cell	CL:0002079	87.30	silver quality
urethra	UBERON:0000057	86.98	gold quality
tibia	UBERON:0000979	86.98	gold quality
muscle of leg	UBERON:0001383	86.76	gold quality
gastrocnemius	UBERON:0001388	86.76	gold quality
lower lobe of lung	UBERON:0008949	86.73	gold quality
renal medulla	UBERON:0000362	86.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.66	gold quality
penis	UBERON:0000989	86.56	gold quality
islet of Langerhans	UBERON:0000006	86.53	gold quality
sperm	CL:0000019	86.52	gold quality
tonsil	UBERON:0002372	86.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.99
E-MTAB-7606	no	90.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

274 targeting STX17, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-25-3P	99.98	74.60	1817

Literature-anchored findings (GeneRIF, showing 34)

• Common variants in the STX17 gene region do not play a key role in the pathogenesis of human melanoma. (PMID:19209086)
• The syntaxin 17 is essential for maintaining the architecture of ERGIC and Golgi. (PMID:21545355)
• Study identifies syntaxin 17 (Stx17) as the autophagosomal SNARE required for fusion with the endosome/lysosome. (PMID:23217709)
• the homotypic fusion and protein sorting-tethering complex promotes autophagosome-lysosome fusion through interaction with STX17 (PMID:24554770)
• Syn17 acts as a switch that responds to nutrient conditions and integrates functions for the endoplasmic reticulum and autophagosomes with mitochondrial dynamics (PMID:25619926)
• This study demonstrates that the amount of syntaxin 17 decreased in Hepatitis C Virus replicating cells. In addition, syntaxin 17 is identified to be a novel factor controlling the release of HCV, and the relevance of autophagosome-lysosome fusion as a regulator of the amount of released viral particles is revealed. (PMID:27099307)
• Pacer recruits PI3KC3 and HOPS complexes to the autophagosome for their site-specific activation by anchoring to the autophagosomal SNARE Stx17. (PMID:28306502)
• L. pneumophila Lpg1137 can shut down ER-mitochondria communication through cleavage of syntaxin 17 (PMID:28504273)
• Data suggest that accumulation of autophagosomes confers cytotoxicity in a number of cell types including neurons mimicking neurodegeneration; RNA interference of combinations of MTOR, VPS33A, and STX17 lead to accumulation of autophagosomes and cytotoxicity. (MTOR = mechanistic target of rapamycin kinase; VPS33A = vacuolar protein sorting 33A; STX17 = syntaxin 17) (PMID:28673965)
• MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation. (PMID:29073720)
• SNARE priming, as exemplified by Syntaxin-17, is essential for maturation of autophagosomes but not for their formation. (PMID:29138318)
• STX17 is targeted specifically to LC3 positive autophagosome membranes. STX17 interacts with LC3 and GABARAP and has binding sites for LC3 at aa 172-175 (LC3-Interaction Region 1 [LIR1]) and aa 189-192 (LIR2). (PMID:29420192)
• Stx17 directly interacts with IRGM, and efficient Stx17 recruitment to autophagosomes requires IRGM. Both IRGM and Stx17 directly interact with mammalian Atg8 proteins, thus being guided to autophagosomes. (PMID:29420192)
• The cytotoxicity of coxsackievirus B3 is associated with a blockage of autophagic flux mediated by reduced STX17 expression. (PMID:29445155)
• Syntaxin 17 promotes lipid droplet formation by regulating the distribution of acyl-CoA synthetase 3 (PMID:29549094)
• MAP1B-LC1 links microtubules and Stx17 in fed cells, and starvation causes the dephosphorylation of MAP1B-LC1 at Thr217, allowing Stx17 to dissociate from MAP1B-LC1 and bind to Atg14L. (PMID:29925525)
• results reveal that the Stx17-PGAM5 axis plays pivotal roles in mitochondrial division and PINK1/Parkin-mediated mitophagy. (PMID:30237312)
• The kinase ULK1 and the apoptosis modulator BRUCE both regulate STX17 engagement during autophagosome maturation in mammalian cells. (PMID:30415939)
• The Stx17 fusion competency is regulated by a phosphosite in its N-peptide, representing a previously unknown regulatory step in mammalian autophagy. (PMID:30655294)
• Stx17 knockout diminished LC3 response and reduced sequestration of the prototypical bulk autophagy cargo lactate dehydrogenase. We conclude that Stx17 is a TBK1 substrate and that together they orchestrate assembly of mammalian pre-autophagosomal structure (PMID:30827897)
• Study demonstrated that the STX17 initiates mitophagy upon depletion of outer mitochondrial membrane protein Fis1. Fis1 loss results in aberrant STX17 accumulation on mitochondria, which exposes the N terminus and promotes self-oligomerization to trigger mitophagy. Findings uncover a PINK1/Parkin-independent mitophagic mechanism in which outer mitochondrial membrane protein Fis1 regulates mitochondrial quality control. (PMID:31053718)
• EACC affects the translocation of SNAREs Stx17 and SNAP29 on autophagosomes without impeding the completion of autophagosomes. EACC treatment also reduces the interaction of Stx17 with the HOPS subunit VPS33A and the cognate lysosomal R-SNARE VAMP8. (PMID:31188703)
• DIPK2A promotes STX17- and VAMP7-mediated autophagosome-lysosome fusion by binding to VAMP7B. (PMID:31251111)
• Acetylation of STX17 (syntaxin 17) controls autophagosome maturation. (PMID:32264736)
• Decoding three distinct states of the Syntaxin17 SNARE motif in mediating autophagosome-lysosome fusion. (PMID:32817423)
• Long non-coding RNA XIST confers aggressive progression via miR-361-3p/STX17 in retinoblastoma cells. (PMID:33155266)
• A SNARE protein Syntaxin 17 captures CFTR to potentiate autophagosomal clearance under stress. (PMID:33191543)
• Circular RNA circ_0000034 upregulates STX17 level to promote human retinoblastoma development via inhibiting miR-361-3p. (PMID:33336726)
• ULK phosphorylation of STX17 controls autophagosome maturation via FLNA. (PMID:37389864)
• The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome-lysosome fusion. (PMID:38182888)
• Human YKT6 forms priming complex with STX17 and SNAP29 to facilitate autophagosome-lysosome fusion. (PMID:38340317)
• SLC34A2 promotes cell proliferation by activating STX17-mediated autophagy in esophageal squamous cell carcinoma. (PMID:38720472)
• Syntaxin 17 recruitment to mature autophagosomes is temporally regulated by PI4P accumulation. (PMID:38831696)
• Exacerbation of atherosclerosis by STX17 knockdown: Unravelling the role of autophagy and inflammation. (PMID:39008328)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stx17	ENSDARG00000006869
mus_musculus	Stx17	ENSMUSG00000061455
rattus_norvegicus	Stx17	ENSRNOG00000005801
drosophila_melanogaster	Syx17	FBGN0035540
caenorhabditis_elegans	syx-17	WBGENE00012150

Paralogs (12): STX7 (ENSG00000079950), STX1B (ENSG00000099365), STX4 (ENSG00000103496), STX1A (ENSG00000106089), STX2 (ENSG00000111450), STX12 (ENSG00000117758), STX16 (ENSG00000124222), STX11 (ENSG00000135604), STX5 (ENSG00000162236), STX3 (ENSG00000166900), TSNARE1 (ENSG00000171045), STX19 (ENSG00000178750)

Protein

Protein identifiers

Syntaxin-17 — P56962 (reviewed: P56962)

All UniProt accessions (5): E9PIC2, E9PJV6, E9PJW1, E9PQU9, P56962

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. STX17 is a SNARE of the autophagosome involved in autophagy through the direct control of autophagosome membrane fusion with the lysosome membrane. May also play a role in the early secretory pathway where it may maintain the architecture of the endoplasmic reticulum-Golgi intermediate compartment/ERGIC and Golgi and/or regulate transport between the endoplasmic reticulum, the ERGIC and the Golgi.

Subunit / interactions. Forms a SNARE complex composed of VAMP8, SNAP29 and STX17 involved in fusion of autophagosome with lysosome. Interacts with VAMP7 and VTI1B. Probably interacts with BET1, SCFD1 and SEC22B. Interacts with PTPN2 and ABL1; involved in STX17 phosphorylation. Interacts with COPB1. Interacts with TMED9 and TMED10; the interaction is direct. Interacts with ATG14. Interacts with RUBCNL/PACER; promoting targeting of RUBCNL/PACER to autophagosome. Interacts with VAMP8, SNAP29, VPS39 and VPS41; these interactions are increased in the absence of TMEM39A. Interacts with IRGM; promoting STX17 recruitment to autophagosomes. Interacts with ATG8 proteins GABARAP and MAP1LC3B. Interacts with RNF115; this interaction enhances STX17 stability which in turn promotes autophagosome maturation. Interacts with RAB39A (GTP-bound); the interaction promotes autophagosome-lysosome membrane fusion driven by STX17-SNAP29-VAMP8. Interacts with RAB39B; the interaction may promote a different fonction in autophagy as compared with RAB39A. (Microbial infection) The interactions with VAMP8, SNAP29 and VPS41 are decreased in presence of SARS coronavirus-2/SARS-CoV-2 ORF3A protein.

Subcellular location. Endoplasmic reticulum membrane. Smooth endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane. Cytoplasmic vesicle. Autophagosome membrane. COPII-coated vesicle membrane. Cytoplasm. Cytosol. Mitochondrion membrane. Autolysosome membrane.

Post-translational modifications. Phosphorylated at Tyr-157 probably by ABL1. Dephosphorylation by PTPN2; regulates exit from the endoplasmic reticulum. (Microbial infection) Cleaved by the L.pneumophila serine protease Lpg1137, impairing endoplasmic reticulum-mitochondria communication, leading to inhibit autophagy.

Similarity. Belongs to the syntaxin family.

RefSeq proteins (1): NP_060389* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000727	T_SNARE_dom	Domain
IPR006012	Syntaxin/epimorphin_CS	Conserved_site
IPR010989	SNARE	Homologous_superfamily
IPR028676	STX17_SNARE	Domain
IPR045242	Syntaxin	Family
IPR059001	STX17_N	Domain

Pfam: PF26585

UniProt features (25 total): mutagenesis site 5, modified residue 4, topological domain 3, sequence conflict 3, helix 2, transmembrane region 2, initiator methionine 1, chain 1, short sequence motif 1, domain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4WY4	X-RAY DIFFRACTION	1.4
7BV4	X-RAY DIFFRACTION	2
7BV6	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56962-F1	70.59	0.41

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 (4): 2, 41, 157, 289

Mutagenesis-validated functional residues (5):

Position	Phenotype
244	alters localization to the autophagosome; when associated with leu-248.
248	alters localization to the autophagosome; when associated with leu-244.
264	alters localization to the autophagosome; when associated with leu-268.
268	alters localization to the autophagosome; when associated with leu-264.
299–300	localizes to the golgi instead of the endoplasmic reticulum.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 228 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, AP1_01, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_MEMBRANE_FUSION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_MACROAUTOPHAGY, GOBP_MEMBRANE_DOCKING, GOBP_EXOCYTOSIS, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (13): intracellular protein transport (GO:0006886), exocytosis (GO:0006887), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), vesicle fusion (GO:0006906), Golgi organization (GO:0007030), autophagosome membrane docking (GO:0016240), protein localization to phagophore assembly site (GO:0034497), obsolete vesicle docking (GO:0048278), autophagosome-lysosome fusion (GO:0061909), endoplasmic reticulum-Golgi intermediate compartment organization (GO:0097111), autophagosome maturation (GO:0097352), autophagy (GO:0006914), vesicle-mediated transport (GO:0016192)

GO Molecular Function (5): SNARE binding (GO:0000149), SNAP receptor activity (GO:0005484), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), protein binding (GO:0005515)

GO Cellular Component (21): autophagosome membrane (GO:0000421), mitochondrion (GO:0005739), autophagosome (GO:0005776), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), ER to Golgi transport vesicle membrane (GO:0012507), COPII-coated ER to Golgi transport vesicle (GO:0030134), smooth endoplasmic reticulum membrane (GO:0030868), SNARE complex (GO:0031201), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), autolysosome membrane (GO:0120281), cytoplasm (GO:0005737), lysosome (GO:0005764), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), HOPS complex (GO:0030897), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	6
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
intracellular protein localization	2
intracellular transport	2
vesicle-mediated transport	2
organelle organization	2
macroautophagy	2
vacuole	2
bounding membrane of organelle	2
membrane protein complex	2
protein transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
intercellular transport	1
Golgi vesicle transport	1
vesicle organization	1
organelle membrane fusion	1
endomembrane system organization	1
autophagosome maturation	1
organelle localization by membrane tethering	1
autophagosome assembly	1
vesicle fusion	1
protein-containing complex disassembly	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
transport	1
cellular process	1
protein binding	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
kinase binding	1
phosphatase binding	1
binding	1
vacuolar membrane	1
autophagosome	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

2054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STX17	SNAP29	O95721	998
STX17	VAMP8	Q9BV40	998
STX17	ATG14	Q6ZNE5	996
STX17	VAMP7	P51809	995
STX17	ATG5	Q9H1Y0	917
STX17	YKT6	O15498	914
STX17	VPS16	Q9H269	837
STX17	ATG13	O75143	831
STX17	VPS33A	Q96AX1	831
STX17	VPS39	Q96JC1	831
STX17	RB1CC1	Q8TDY2	817
STX17	NR4A3	Q92570	812
STX17	EPG5	Q9HCE0	803
STX17	PRDX5	P30044	784
STX17	ULK1	O75385	781

IntAct

113 interactions, top by confidence:

A	B	Type	Score
VAMP8	SNAP29	psi-mi:“MI:0914”(association)	0.830
STX17	SNAP29	psi-mi:“MI:0914”(association)	0.810
SNAP29	STX17	psi-mi:“MI:0915”(physical association)	0.810
SNAP29	STX17	psi-mi:“MI:0914”(association)	0.810
SNAP29	STX17	psi-mi:“MI:0403”(colocalization)	0.810
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
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
VPS39	STX17	psi-mi:“MI:0915”(physical association)	0.590
STX17	VPS41	psi-mi:“MI:0915”(physical association)	0.590
VPS41	STX17	psi-mi:“MI:0915”(physical association)	0.590
STX17	VPS33A	psi-mi:“MI:0915”(physical association)	0.540
VPS16	STX17	psi-mi:“MI:0915”(physical association)	0.540
STX17	VPS33A	psi-mi:“MI:0914”(association)	0.540
VPS33A	STX17	psi-mi:“MI:0914”(association)	0.540
VPS33A	STX17	psi-mi:“MI:0403”(colocalization)	0.540
STX17	VPS16	psi-mi:“MI:0403”(colocalization)	0.540
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530

BioGRID (303): VPS33A (Affinity Capture-MS), VPS16 (Affinity Capture-MS), VPS33A (Affinity Capture-Western), VPS16 (Affinity Capture-Western), VPS11 (Affinity Capture-Western), VPS18 (Affinity Capture-Western), VPS39 (Affinity Capture-Western), VPS41 (Affinity Capture-Western), STX17 (Affinity Capture-MS), STX17 (Affinity Capture-MS), STX17 (Affinity Capture-MS), STX17 (Affinity Capture-MS), STX17 (Affinity Capture-RNA), STX17 (Affinity Capture-Western), STX17 (Two-hybrid)

ESM2 similar proteins: O08522, O14662, O22151, O49160, O60499, O64791, O73787, O88384, O88630, O88983, O95249, P56962, P58200, Q08851, Q08DB5, Q13190, Q2KIU0, Q2TBU3, Q40554, Q4VBI7, Q5E9Y2, Q5RBL6, Q5REB4, Q62931, Q63635, Q68FW4, Q6DDF4, Q7ZTY7, Q8BVI5, Q8K1E0, Q8VDS8, Q944A9, Q946Y7, Q94KK7, Q9CQ56, Q9D0I4, Q9LMP7, Q9LNH6, Q9LRP1, Q9NZ43

Diamond homologs: P56962, Q5E9Y2, Q5RBW6, Q84R43, Q9D0I4, Q9ER00, Q9Z158, G3V7P1, O15400, O64791, O70257, P32854, P70452, P91409, Q08850, Q12846, Q3SWZ3, Q3ZBT5, Q42374, Q54JY7, Q54X86, Q5R602, Q5TX47, Q6F3B4, Q7KVY7, Q7XIE2, Q8VZU2, Q9SRV7, Q9SVC2, Q9SXB0, Q9ZPV9, Q9ZQZ8, Q9ZSD4

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
RUBCNL	“up-regulates activity”	STX17	binding
STX17	“form complex”	“STX17-VAMP8 SNARE complex”	binding
TBK1	“up-regulates activity”	STX17	phosphorylation
ABL1	“down-regulates activity”	STX17	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
ER-Phagosome pathway	5	9.0×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
endosomal vesicle fusion	6	73.3×	5e-08
endosome to lysosome transport	6	22.0×	9e-05
autophagosome maturation	5	19.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1295 predictions. Top by Δscore:

Variant	Effect	Δscore
9:99915174:TTAG:T	acceptor_loss	1.0000
9:99915176:A:G	acceptor_loss	1.0000
9:99915332:GT:G	donor_gain	1.0000
9:99915333:TT:T	donor_gain	1.0000
9:99915359:GAAG:G	donor_gain	1.0000
9:99915360:AAGG:A	donor_loss	1.0000
9:99915361:AGG:A	donor_loss	1.0000
9:99915363:G:GC	donor_loss	1.0000
9:99928772:A:AG	acceptor_gain	1.0000
9:99928773:T:G	acceptor_gain	1.0000
9:99928773:TATA:T	acceptor_loss	1.0000
9:99928773:TATAG:T	acceptor_gain	1.0000
9:99928774:A:AG	acceptor_gain	1.0000
9:99928774:ATAG:A	acceptor_loss	1.0000
9:99928774:ATAGT:A	acceptor_gain	1.0000
9:99928775:T:G	acceptor_gain	1.0000
9:99928775:TA:T	acceptor_loss	1.0000
9:99928775:TAGTA:T	acceptor_gain	1.0000
9:99928776:A:AG	acceptor_gain	1.0000
9:99928776:AGTA:A	acceptor_loss	1.0000
9:99928776:AGTAT:A	acceptor_gain	1.0000
9:99928777:G:GG	acceptor_gain	1.0000
9:99928777:GT:G	acceptor_gain	1.0000
9:99928777:GTAT:G	acceptor_gain	1.0000
9:99928777:GTATC:G	acceptor_gain	1.0000
9:99928840:TCAGG:T	donor_loss	1.0000
9:99928841:CAGG:C	donor_loss	1.0000
9:99928842:AGG:A	donor_loss	1.0000
9:99928843:GGTAA:G	donor_loss	1.0000
9:99928844:G:GG	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003731 (9:99929499 A>C,G), RS1000087743 (9:99913903 T>C), RS1000099812 (9:99958042 T>C), RS1000158175 (9:99936533 T>A,G), RS1000204110 (9:99906887 T>G), RS1000241819 (9:99923644 A>G), RS1000268760 (9:99907371 T>C), RS1000507866 (9:99946599 A>C,G), RS1000512870 (9:99956712 T>G), RS1000523361 (9:99913561 T>C,G), RS1000604828 (9:99908814 C>A,G), RS1000659598 (9:99952890 AG>A,AGGGGGGG), RS1000676386 (9:99917445 G>A), RS1000721156 (9:99940560 C>A,T), RS1000728152 (9:99916973 G>C)

Disease associations

OMIM: gene MIM:604204 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000719_4	Alopecia areata	4.000000e-07
GCST010397_104	Gut microbiota (bacterial taxa, rank normal transformation method)	1.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
entinostat	affects cotreatment, decreases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Plant Extracts	increases expression, affects cotreatment	1
Selenomethionine	affects expression	1
Vitamin E	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HU	Abcam HeLa STX17 KO	Cancer cell line	Female
CVCL_TR08	HAP1 STX17 (-) 1	Cancer cell line	Male
CVCL_XU01	HAP1 STX17 (-) 2	Cancer cell line	Male
CVCL_XU02	HAP1 STX17 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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