SYT3

Summary

SYT3 (synaptotagmin 3, HGNC:11511) is a protein-coding gene on chromosome 19q13.33, encoding Synaptotagmin-3 (Q9BQG1). Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain.

Predicted to enable several functions, including calcium ion sensor activity; phospholipid binding activity; and protein dimerization activity. Involved in positive regulation of dendrite extension. Located in endosome.

Source: NCBI Gene 84258 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_001160329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11511
Approved symbol	SYT3
Name	synaptotagmin 3
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213023
Ensembl biotype	protein_coding
OMIM	600327
Entrez	84258

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000338916, ENST00000593901, ENST00000595117, ENST00000595557, ENST00000598997, ENST00000600079, ENST00000897663, ENST00000897664, ENST00000897665, ENST00000897666, ENST00000936903, ENST00000936904, ENST00000936905, ENST00000936906, ENST00000936907, ENST00000964191

RefSeq mRNA: 9 — MANE Select: NM_001160329 NM_001160328, NM_001160329, NM_001424344, NM_001424345, NM_001424346, NM_001424347, NM_001424348, NM_001424349, NM_032298

CCDS: CCDS12798

Canonical transcript exons

ENST00000600079 — 11 exons

Exon	Start	End
ENSE00000721745	50629294	50629512
ENSE00000721746	50625897	50626017
ENSE00000869333	50632286	50632811
ENSE00000954899	50629784	50630171
ENSE00002296653	50639025	50639162
ENSE00003032980	50637264	50637426
ENSE00003049413	50639790	50639881
ENSE00003150970	50621977	50622481
ENSE00003514960	50622687	50622755
ENSE00003519687	50625393	50625564
ENSE00003667811	50625162	50625294

Expression profiles

Bgee: expression breadth ubiquitous, 112 present calls, max score 90.56.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8199 / max 54.2742, expressed in 209 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182239	0.3550	87
182240	0.3447	161
182238	0.1202	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	90.56	gold quality
cortical plate	UBERON:0005343	90.47	gold quality
superior frontal gyrus	UBERON:0002661	90.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.73	gold quality
cerebellum	UBERON:0002037	88.29	gold quality
cerebellar cortex	UBERON:0002129	88.21	gold quality
cerebellar hemisphere	UBERON:0002245	88.20	gold quality
prefrontal cortex	UBERON:0000451	88.00	gold quality
frontal cortex	UBERON:0001870	87.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.19	gold quality
right frontal lobe	UBERON:0002810	87.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.00	gold quality
cerebral cortex	UBERON:0000956	86.45	gold quality
anterior cingulate cortex	UBERON:0009835	85.55	gold quality
Ammon’s horn	UBERON:0001954	84.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.96	gold quality
hypothalamus	UBERON:0001898	83.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.18	gold quality
brain	UBERON:0000955	82.92	gold quality
temporal lobe	UBERON:0001871	81.98	gold quality
amygdala	UBERON:0001876	81.74	gold quality
nucleus accumbens	UBERON:0001882	80.81	gold quality
putamen	UBERON:0001874	80.47	gold quality
caudate nucleus	UBERON:0001873	79.30	gold quality
substantia nigra	UBERON:0002038	79.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.12	gold quality
ganglionic eminence	UBERON:0004023	69.88	gold quality
pituitary gland	UBERON:0000007	67.44	gold quality
adenohypophysis	UBERON:0002196	66.71	gold quality
stromal cell of endometrium	CL:0002255	66.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting SYT3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-7114-3P	98.42	66.53	569
HSA-MIR-1180-5P	98.16	65.32	460

Literature-anchored findings (GeneRIF, showing 1)

• the extended synaptotagmins (E-Syts), endoplasmic reticulum (ER) proteins that function as PtdIns(4,5)P2- and Ca(2+)-regulated tethers to the Pplasma membrane. (PMID:27065097)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	syt3	ENSDARG00000075830
mus_musculus	Syt3	ENSMUSG00000030731
rattus_norvegicus	Syt3	ENSRNOG00000019318

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), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Synaptotagmin-3 — Q9BQG1 (reviewed: Q9BQG1)

Alternative names: Synaptotagmin III

All UniProt accessions (3): Q9BQG1, M0QY70, M0QYH4

UniProt curated annotations — full annotation on UniProt →

Function. Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain. Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis. Plays a role in dendrite formation by melanocytes.

Subunit / interactions. Homodimer; disulfide-linked via the cysteine motif. Can also form heterodimers with SYT6, SYT9 and SYT10.

Subcellular location. Cell membrane. Cytoplasmic vesicle. Secretory vesicle membrane.

Tissue specificity. Expressed in melanocytes.

Cofactor. Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.

Domain organisation. The cysteine motif mediates homo- or heterodimer formation via formation of disulfide bonds. The first C2 domain mediates Ca(2+)-dependent phospholipid binding.

Similarity. Belongs to the synaptotagmin family.

RefSeq proteins (10): NP_001153800, NP_001153801, NP_001411273, NP_001411274, NP_001411275, NP_001411276, NP_001411277, NP_001411278, NP_001411279, NP_115674 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001565	Synaptotagmin	Domain
IPR035892	C2_domain_sf	Homologous_superfamily

Pfam: PF00168

UniProt features (33 total): binding site 16, region of interest 4, compositionally biased region 3, topological domain 2, sequence conflict 2, domain 2, chain 1, transmembrane region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQG1-F1	70.61	0.40

Functional residue map

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

Ligand- & substrate-binding residues (16): 330; 330; 336; 388; 388; 389; 390; 390; 390; 393; 396; 396 …

Post-translational modifications (1): 284

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_VESICLE_ORGANIZATION, AAGCCAT_MIR135A_MIR135B, GOBP_MEMBRANE_FUSION, GOBP_GROWTH, GOBP_REGULATION_OF_EXOCYTOSIS, AREB6_01, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GGAMTNNNNNTCCY_UNKNOWN, USF_C

GO Biological Process (6): chemical synaptic transmission (GO:0007268), vesicle-mediated transport (GO:0016192), regulation of calcium ion-dependent exocytosis (GO:0017158), cell differentiation (GO:0030154), positive regulation of vesicle fusion (GO:0031340), positive regulation of dendrite extension (GO:1903861)

GO Molecular Function (5): SNARE binding (GO:0000149), calcium-dependent phospholipid binding (GO:0005544), metal ion binding (GO:0046872), calcium ion sensor activity (GO:0061891), protein binding (GO:0005515)

GO Cellular Component (7): endosome (GO:0005768), plasma membrane (GO:0005886), transport vesicle membrane (GO:0030658), synapse (GO:0045202), exocytic vesicle (GO:0070382), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport vesicle	2
anterograde trans-synaptic signaling	1
transport	1
cellular process	1
calcium-ion regulated exocytosis	1
regulation of regulated secretory pathway	1
cellular developmental process	1
vesicle fusion	1
positive regulation of organelle organization	1
regulation of vesicle fusion	1
positive regulation of transport	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
dendrite extension	1
regulation of dendrite extension	1
protein binding	1
phospholipid binding	1
cation binding	1
calcium ion binding	1
metal ion sensor activity	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cell junction	1
secretory vesicle	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYT3	KLK4	Q9Y5K2	600
SYT3	C19orf81	C9J6K1	530
SYT3	VAMP2	P19065	504
SYT3	SHANK1	Q9Y566	503
SYT3	SYT8	Q8NBV8	471
SYT3	CTU1	Q7Z7A3	447
SYT3	DHX34	Q14147	436
SYT3	EMC10	Q5UCC4	434
SYT3	KCNK16	Q96T55	433
SYT3	STX1A	Q16623	427
SYT3	LRRIQ3	A6PVS8	421
SYT3	ETNPPL	Q8TBG4	411
SYT3	STXBP1	P61764	411
SYT3	CAMK2B	Q13554	406
SYT3	SNAP25	P13795	396

IntAct

41 interactions, top by confidence:

A	B	Type	Score
KCNJ6	SYT3	psi-mi:“MI:0915”(physical association)	0.560
MRM1	SYT3	psi-mi:“MI:0915”(physical association)	0.560
SYT3	CTSD	psi-mi:“MI:0915”(physical association)	0.560
SYT3		psi-mi:“MI:0915”(physical association)	0.560
SYT3	NEFL	psi-mi:“MI:0915”(physical association)	0.560
SYT3	WFS1	psi-mi:“MI:0915”(physical association)	0.560
SYT3	RNF11	psi-mi:“MI:0915”(physical association)	0.560
HTT	SYT3	psi-mi:“MI:0915”(physical association)	0.560
SYT3	PGK2	psi-mi:“MI:0914”(association)	0.530

BioGRID (32): SYT3 (Affinity Capture-MS), SYT3 (Affinity Capture-MS), SYT10 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), FNDC3A (Affinity Capture-MS), MYH7 (Affinity Capture-MS), MADD (Affinity Capture-MS), PGK2 (Affinity Capture-MS), LMF2 (Affinity Capture-MS), SYT3 (Two-hybrid), MRM1 (Two-hybrid), SYNCRIP (Reconstituted Complex), SNAP25 (Reconstituted Complex), SYT3 (Affinity Capture-Western), SYT3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8P0N4K0, A2AB59, B4F7F3, D3YZU1, D3ZD05, O35681, O75427, O95382, P22455, P22607, P40748, P55144, P70218, Q06418, Q14160, Q1LZH7, Q2PS20, Q32P44, Q495M9, Q4ACU6, Q4H4B6, Q505F5, Q5F488, Q61851, Q63ZY3, Q6P9K8, Q6TLK4, Q6ZUM4, Q7KRY7, Q80T11, Q80U72, Q8BH60, Q8BX02, Q8N1G4, Q8TE68, Q8VC03, Q8VHK1, Q8VHK2, Q8WXD9, Q8WXE0

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1141 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50622479:GACC:G	acceptor_loss	1.0000
19:50622480:ACC:A	acceptor_loss	1.0000
19:50622482:C:CA	acceptor_loss	1.0000
19:50622682:CTTAC:C	donor_loss	1.0000
19:50622683:TTA:T	donor_loss	1.0000
19:50622685:A:AC	donor_gain	1.0000
19:50622685:AC:A	donor_gain	1.0000
19:50622685:ACC:A	donor_gain	1.0000
19:50622685:ACCC:A	donor_gain	1.0000
19:50622685:ACCCC:A	donor_loss	1.0000
19:50622686:C:CC	donor_gain	1.0000
19:50622686:C:CG	donor_loss	1.0000
19:50622686:CC:C	donor_gain	1.0000
19:50622686:CCC:C	donor_gain	1.0000
19:50622686:CCCC:C	donor_gain	1.0000
19:50622686:CCCCT:C	donor_gain	1.0000
19:50622754:TC:T	acceptor_gain	1.0000
19:50622755:CC:C	acceptor_gain	1.0000
19:50622756:C:CC	acceptor_gain	1.0000
19:50625158:TCA:T	donor_loss	1.0000
19:50625159:CA:C	donor_loss	1.0000
19:50625160:A:AC	donor_gain	1.0000
19:50625160:ACCT:A	donor_gain	1.0000
19:50625160:ACCTC:A	donor_gain	1.0000
19:50625161:C:CC	donor_gain	1.0000
19:50625161:C:G	donor_loss	1.0000
19:50625161:CCT:C	donor_gain	1.0000
19:50625161:CCTC:C	donor_gain	1.0000
19:50625161:CCTCC:C	donor_gain	1.0000
19:50625290:CGA:C	acceptor_gain	1.0000

AlphaMissense

3773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50625169:A:G	L567P	1.000
19:50625169:A:T	L567Q	1.000
19:50625197:G:T	R558S	1.000
19:50625211:A:C	M553R	1.000
19:50625211:A:T	M553K	1.000
19:50625219:C:A	W550C	1.000
19:50625219:C:G	W550C	1.000
19:50625220:C:G	W550S	1.000
19:50625221:A:G	W550R	1.000
19:50625221:A:T	W550R	1.000
19:50625271:C:A	G533V	1.000
19:50625271:C:T	G533D	1.000
19:50625272:C:A	G533C	1.000
19:50625272:C:G	G533R	1.000
19:50625274:A:T	I532N	1.000
19:50625283:T:A	N529I	1.000
19:50625289:C:A	G527V	1.000
19:50625289:C:T	G527E	1.000
19:50625290:C:A	G527W	1.000
19:50625290:C:G	G527R	1.000
19:50625290:C:T	G527R	1.000
19:50625395:G:C	D524E	1.000
19:50625395:G:T	D524E	1.000
19:50625396:T:A	D524V	1.000
19:50625396:T:C	D524G	1.000
19:50625396:T:G	D524A	1.000
19:50625397:C:A	D524Y	1.000
19:50625397:C:G	D524H	1.000
19:50625397:C:T	D524N	1.000
19:50625400:A:C	Y523D	1.000

dbSNP variants (sampled 300 via entrez): RS1000082429 (19:50627227 ACT>A), RS1000149458 (19:50629537 C>T), RS1000200536 (19:50634109 T>C), RS1000280466 (19:50640347 A>G), RS1000626472 (19:50633876 G>A,T), RS1000990959 (19:50622111 T>C), RS1001100713 (19:50631392 G>A), RS1001363111 (19:50641521 T>A,C), RS1001388664 (19:50624544 T>G), RS1001402538 (19:50624899 C>T), RS1001494703 (19:50623914 A>G), RS1001660773 (19:50636766 C>T), RS1001923567 (19:50624031 T>C), RS1001954124 (19:50630531 T>C), RS1002446602 (19:50625373 G>A,C,T)

Disease associations

OMIM: gene MIM:600327 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008151_86	Waist circumference	4.000000e-07
GCST008160_118	Waist circumference	4.000000e-07
GCST009219_8	Superior frontal gyrus volume	2.000000e-06
GCST010988_313	Adult body size	4.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
abrine	decreases expression	1
Decitabine	decreases expression, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Niclosamide	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression, decreases reaction	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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