SYT15

Summary

SYT15 (synaptotagmin 15, HGNC:17167) is a protein-coding gene on chromosome 10q11.22, encoding Synaptotagmin-15 (Q9BQS2). May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. It is a selective cancer dependency (DepMap: 40.0% of cell lines).

This gene encodes a member of the Synaptotagmin (Syt) family of membrane trafficking proteins. Members of this family contain a transmembrane region and a C-terminal-type tandem C2 domain. Unlike related family members, the encoded protein may be involved in membrane trafficking in non-neuronal tissues. Two trancript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 83849 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 81 total
• Cancer dependency (DepMap): dependent in 40.0% of screened cell lines
• MANE Select transcript: NM_031912

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17167
Approved symbol	SYT15
Name	synaptotagmin 15
Location	10q11.22
Locus type	gene with protein product
Status	Approved
Aliases	CHR10SYT
Ensembl gene	ENSG00000204176
Ensembl biotype	protein_coding
OMIM	608081
Entrez	83849

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374321, ENST00000374323, ENST00000374328, ENST00000449358, ENST00000503753, ENST00000512997, ENST00000907760, ENST00000907761

RefSeq mRNA: 2 — MANE Select: NM_031912 NM_031912, NM_181519

CCDS: CCDS73103, CCDS73104

Canonical transcript exons

ENST00000374321 — 8 exons

Exon	Start	End
ENSE00001463152	46585598	46585777
ENSE00001463165	46584495	46584615
ENSE00001463168	46583732	46583902
ENSE00001748738	46581896	46582191
ENSE00001801077	46580164	46580368
ENSE00002019747	46579128	46579175
ENSE00002488473	46580894	46581036
ENSE00003893560	46587505	46592064

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 78.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2164 / max 28.1643, expressed in 86 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104815	0.1122	44
104812	0.0856	37
104813	0.0107	4
104814	0.0079	0

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.53	gold quality
right lung	UBERON:0002167	77.45	gold quality
upper lobe of left lung	UBERON:0008952	77.18	gold quality
lung	UBERON:0002048	76.31	gold quality
left uterine tube	UBERON:0001303	76.12	gold quality
ectocervix	UBERON:0012249	75.16	gold quality
apex of heart	UBERON:0002098	74.82	gold quality
mucosa of stomach	UBERON:0001199	73.77	gold quality
lymph node	UBERON:0000029	72.79	gold quality
endocervix	UBERON:0000458	72.62	gold quality
subcutaneous adipose tissue	UBERON:0002190	72.49	gold quality
uterine cervix	UBERON:0000002	72.41	gold quality
placenta	UBERON:0001987	71.95	gold quality
vagina	UBERON:0000996	71.94	gold quality
adipose tissue	UBERON:0001013	71.80	gold quality
body of pancreas	UBERON:0001150	71.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.51	gold quality
lower esophagus	UBERON:0013473	71.49	gold quality
fallopian tube	UBERON:0003889	71.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	71.13	gold quality
omental fat pad	UBERON:0010414	71.06	gold quality
myometrium	UBERON:0001296	71.04	gold quality
body of uterus	UBERON:0009853	70.96	gold quality
esophagus	UBERON:0001043	70.72	gold quality
urinary bladder	UBERON:0001255	70.65	gold quality
right lobe of thyroid gland	UBERON:0001119	70.54	gold quality
tibial nerve	UBERON:0001323	70.47	gold quality
right coronary artery	UBERON:0001625	70.21	gold quality
left coronary artery	UBERON:0001626	70.03	gold quality
esophagus mucosa	UBERON:0002469	69.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

136 targeting SYT15, 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-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-545-3P	99.95	70.74	2783

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 40.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• molecular cloning and structure (PMID:12788067)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	syt15	ENSDARG00000079926
mus_musculus	Syt15	ENSMUSG00000041479
rattus_norvegicus	Syt15	ENSRNOG00000051688

Paralogs (31): SYT7 (ENSG00000011347), SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYTL4 (ENSG00000102362), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT11 (ENSG00000132718), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYTL2 (ENSG00000137501), SYT16 (ENSG00000139973), SYTL1 (ENSG00000142765), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), SYTL3 (ENSG00000164674), TC2N (ENSG00000165929), SYT9 (ENSG00000170743), SYT12 (ENSG00000173227), RPH3AL (ENSG00000181031), C2CD4C (ENSG00000183186), C2CD4A (ENSG00000198535), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Synaptotagmin-15 — Q9BQS2 (reviewed: Q9BQS2)

Alternative names: Chr10Syt, Synaptotagmin XV

All UniProt accessions (3): D6RF99, Q9BQS2, H3BLX3

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane Cell membrane Cell membrane.

Domain organisation. Neither C2 domains mediates Ca(2+)-dependent or -independent phospholipid binding.

Similarity. Belongs to the synaptotagmin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BQS2-1	1, Syt XV-a	yes
Q9BQS2-2	2, Syt XV-b
Q9BQS2-3	3
Q9BQS2-4	4

RefSeq proteins (2): NP_114118, NP_852660 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR047897	Synaptotagmin-15/17_C2A	Domain

Pfam: PF00168

UniProt features (13 total): splice variant 4, topological domain 2, sequence conflict 2, domain 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQS2-F1	77.25	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS, GOBP_SECRETION, GOBP_REGULATION_OF_REGULATED_SECRETORY_PATHWAY, GOBP_REGULATION_OF_CALCIUM_ION_DEPENDENT_EXOCYTOSIS, GOBP_CALCIUM_ION_REGULATED_EXOCYTOSIS, GOBP_REGULATION_OF_TRANSPORT, GOCC_EXOCYTIC_VESICLE, GOCC_SECRETORY_VESICLE, GOMF_SNARE_BINDING, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING, GOMF_CALCIUM_DEPENDENT_PHOSPHOLIPID_BINDING

GO Biological Process (2): vesicle-mediated transport (GO:0016192), regulation of calcium ion-dependent exocytosis (GO:0017158)

GO Molecular Function (4): SNARE binding (GO:0000149), calcium-dependent phospholipid binding (GO:0005544), calcium ion sensor activity (GO:0061891), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), exocytic vesicle (GO:0070382), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
cellular process	1
calcium-ion regulated exocytosis	1
regulation of regulated secretory pathway	1
protein binding	1
phospholipid binding	1
calcium ion binding	1
metal ion sensor activity	1
binding	1
membrane	1
cell periphery	1
transport vesicle	1
secretory vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYT15	GPRIN2	O60269	537
SYT15	ANTXRL	A6NF34	482
SYT15	NPY4R2	P0DQD5	399
SYT15	ASB14	A6NK59	384
SYT15	FRMPD2	Q68DX3	380
SYT15	AGAP6	Q5VW22	380
SYT15	KNCN	A6PVL3	369
SYT15	TMEM161A	Q9NX61	363
SYT15	ALG14	Q96F25	359
SYT15	SNAP25	P13795	357
SYT15	COLQ	Q9Y215	330
SYT15	FAM25A	B3EWG3	324
SYT15	ASAH2B	P0C7U1	322
SYT15	RAPSN	Q13702	316
SYT15	ZNF510	Q9Y2H8	311

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): SYT15 (Affinity Capture-MS), SYT15 (Two-hybrid), LOC102724488 (Two-hybrid), SYT15 (Two-hybrid), LOC102724488 (Two-hybrid), SYT15 (Two-hybrid), LOC102724488 (Two-hybrid), SYT15 (Two-hybrid), LOC102724488 (Two-hybrid), SYT15 (Two-hybrid), LOC102724488 (Two-hybrid), SYT15 (Affinity Capture-MS), SYT15 (Affinity Capture-MS), C6orf211 (Cross-Linking-MS (XL-MS)), SYT15 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A2AWP8, A2RRH5, C9J798, O43374, O70277, O95294, P04629, P59926, Q0GA42, Q13368, Q14318, Q16512, Q29RM4, Q2HY40, Q2T9P3, Q2TBA3, Q5BIM1, Q5M7W1, Q5R5M3, Q5R811, Q5T7P8, Q5XIS9, Q62746, Q6PFQ7, Q6PFY8, Q7TNM2, Q7TP90, Q7Z4K8, Q8BG60, Q8BHT7, Q8BQC3, Q8C6N3, Q8CIW5, Q8IZ69, Q8NCT1, Q920N2, Q92546, Q925B4

Diamond homologs: A0A075F932, A0FGR8, A4IJ05, K8FE10, O00445, O00750, O08625, O08835, O35681, O43581, P04409, P05128, P05129, P05130, P05696, P10102, P10829, P13677, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P41885, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1759 predictions. Top by Δscore:

Variant	Effect	Δscore
10:46582190:C:CA	donor_loss	1.0000
10:46582191:A:AT	donor_loss	1.0000
10:46582192:TACCT:T	donor_loss	1.0000
10:46582193:GTACC:G	donor_loss	1.0000
10:46582194:TGTA:T	donor_loss	1.0000
10:46583729:C:CC	acceptor_gain	1.0000
10:46583729:C:T	acceptor_gain	1.0000
10:46583730:CC:C	acceptor_gain	1.0000
10:46583731:AC:A	acceptor_gain	1.0000
10:46583732:CAC:C	acceptor_gain	1.0000
10:46583732:CACC:C	acceptor_gain	1.0000
10:46583733:ACAC:A	acceptor_gain	1.0000
10:46583734:GACAC:G	acceptor_gain	1.0000
10:46583796:T:TA	donor_gain	1.0000
10:46583899:T:TA	donor_gain	1.0000
10:46583901:C:A	donor_loss	1.0000
10:46583902:AC:A	donor_loss	1.0000
10:46583902:ACCTC:A	donor_loss	1.0000
10:46583903:TACCT:T	donor_loss	1.0000
10:46583904:ATAC:A	donor_loss	1.0000
10:46583905:CATA:C	donor_loss	1.0000
10:46584481:A:T	acceptor_gain	1.0000
10:46584482:C:CT	acceptor_gain	1.0000
10:46584492:C:CA	acceptor_loss	1.0000
10:46584492:C:CC	acceptor_gain	1.0000
10:46584493:GC:G	acceptor_loss	1.0000
10:46584493:GCTG:G	acceptor_loss	1.0000
10:46584495:GGG:G	acceptor_gain	1.0000
10:46584496:GGGG:G	acceptor_gain	1.0000
10:46584497:GGGGG:G	acceptor_gain	1.0000

AlphaMissense

2736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:46585607:T:A	V318D	0.996
10:46587573:T:A	W398R	0.995
10:46587573:T:C	W398R	0.995
10:46587534:G:C	G385R	0.994
10:46587575:G:C	W398C	0.994
10:46587575:G:T	W398C	0.994
10:46584517:T:C	L282P	0.993
10:46585650:G:C	K332N	0.993
10:46585650:G:T	K332N	0.993
10:46585619:T:C	L322P	0.992
10:46585706:T:C	F351S	0.992
10:46587535:G:A	G385D	0.992
10:46584529:T:C	L286P	0.991
10:46584556:T:C	L295P	0.991
10:46587615:T:A	W412R	0.991
10:46587615:T:C	W412R	0.991
10:46584562:T:A	V297E	0.990
10:46585742:T:C	L363P	0.990
10:46585738:A:C	S362R	0.989
10:46585740:C:A	S362R	0.989
10:46585740:C:G	S362R	0.989
10:46587574:G:C	W398S	0.989
10:46585705:T:C	F351L	0.988
10:46585707:C:A	F351L	0.988
10:46585707:C:G	F351L	0.988
10:46582031:T:C	L164P	0.987
10:46584553:G:C	R294P	0.987
10:46584568:T:A	V299E	0.987
10:46587535:G:T	G385V	0.987
10:46585748:T:C	L365P	0.986

dbSNP variants (sampled 300 via entrez): RS10545241 (10:46594606 AGAC>A), RS10588658 (10:46580719 CGTGTGTGT>C,CGT,CGTGT,CGTGTGT,CGTGTGTGTGT), RS10588659 (10:46580680 CTGTGTGTGTGTGTGTGTGTGTGTGTG>C,CTG,CTGTG,CTGTGTGTG,CTGTGTGTGTGTG,CTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG,CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG), RS10712659 (10:46586841 CAAAAA>C,CAA,CAAA,CAAAA,CAAAAAA,CAAAAAAAAA), RS111273873 (10:46578735 A>G), RS111596780 (10:46586805 A>C,G), RS111625798 (10:46579453 C>A,T), RS111852046 (10:46584752 C>T), RS111926928 (10:46579627 G>T), RS112001859 (10:46578821 C>T), RS11204657 (10:46592826 C>G), RS112255958 (10:46589134 G>A), RS112965082 (10:46583722 TC>T,TCC,TCCC), RS113324281 (10:46584716 A>C), RS113796296 (10:46584214 C>A,T)

Disease associations

OMIM: gene MIM:608081 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
Dasatinib	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Glucose	increases expression	1
Smoke	increases expression	1
Thalidomide	decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Acrylamide	decreases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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