SYT13

Summary

SYT13 (synaptotagmin 13, HGNC:14962) is a protein-coding gene on chromosome 11p11.2, encoding Synaptotagmin-13 (Q7L8C5). May be involved in transport vesicle docking to the plasma membrane.

This gene encodes a member of the large synaptotagmin protein family. Family members have an extracellular N-terminal transmembrane domain and a cytoplasmic C terminus with two tandem C2 domains (C2A and C2B). Synaptotogmin family members can form homo- and heteromeric complexes with each other. They also have different biochemical properties and developmental profiles, and patterns of tissue distribution. Synaptotagmins function as membrane traffickers in multicellular organisms. Two alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Source: NCBI Gene 57586 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_020826

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14962
Approved symbol	SYT13
Name	synaptotagmin 13
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1427
Ensembl gene	ENSG00000019505
Ensembl biotype	protein_coding
OMIM	607716
Entrez	57586

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000020926, ENST00000528101, ENST00000533332

RefSeq mRNA: 2 — MANE Select: NM_020826 NM_001247987, NM_020826

CCDS: CCDS31470

Canonical transcript exons

ENST00000020926 — 6 exons

Exon	Start	End
ENSE00000711706	45286025	45286341
ENSE00001329248	45240302	45244356
ENSE00003467951	45255666	45255891
ENSE00003512287	45254270	45254404
ENSE00003528155	45252421	45252722
ENSE00003661676	45246383	45246512

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 99.21.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0283 / max 250.4812, expressed in 329 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119472	3.6960	319
119470	0.2139	85
119471	0.1183	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.21	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.54	gold quality
endothelial cell	CL:0000115	98.01	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.95	gold quality
cortical plate	UBERON:0005343	97.90	gold quality
islet of Langerhans	UBERON:0000006	96.63	gold quality
pons	UBERON:0000988	96.44	gold quality
substantia nigra pars compacta	UBERON:0001965	96.02	gold quality
superior frontal gyrus	UBERON:0002661	96.00	gold quality
postcentral gyrus	UBERON:0002581	95.95	gold quality
parietal lobe	UBERON:0001872	95.62	gold quality
entorhinal cortex	UBERON:0002728	95.24	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.18	gold quality
primary visual cortex	UBERON:0002436	95.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.27	gold quality
occipital lobe	UBERON:0002021	94.06	gold quality
prefrontal cortex	UBERON:0000451	93.12	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.92	gold quality
frontal cortex	UBERON:0001870	92.88	gold quality
colonic mucosa	UBERON:0000317	92.66	gold quality
neocortex	UBERON:0001950	92.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.66	gold quality
cerebellar vermis	UBERON:0004720	91.63	gold quality
superior vestibular nucleus	UBERON:0007227	91.37	gold quality
cerebral cortex	UBERON:0000956	91.33	gold quality
right frontal lobe	UBERON:0002810	90.89	gold quality
lateral globus pallidus	UBERON:0002476	89.80	gold quality
temporal lobe	UBERON:0001871	89.62	gold quality
anterior cingulate cortex	UBERON:0009835	89.58	gold quality
cingulate cortex	UBERON:0003027	89.54	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	421.21
E-GEOD-83139	yes	299.17
E-ENAD-27	yes	292.31
E-GEOD-93593	yes	146.12
E-HCAD-31	yes	30.26
E-GEOD-81608	yes	24.92
E-GEOD-81547	yes	10.76
E-GEOD-125970	yes	6.98
E-ANND-3	yes	4.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting SYT13, 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-4455	100.00	65.48	1587
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-548AV-5P	99.60	70.84	2107

Literature-anchored findings (GeneRIF, showing 12)

• human SYT13 functions as a liver tumor suppressor gene that complements a molecular defect in rat liver tumor cells resulting in a normalized cellular phenotype in vitro and suppression of tumorigenicity in vivo (PMID:18202767)
• These studies combine to suggest that SYT13 is a liver tumor suppressor gene and that its function may be mediated through pathways implicated in mesenchymal to epithelial transition (PMID:20840848)
• SYT13 expression in gastric cancer is associated with peritoneal metastases. (PMID:29741294)
• SYT13 levels were significantly associated with shorter peritoneal recurrence-free survival (PRFS) and overall survival in patients with gastric cancer; positive levels of SYT13 and CEA mRNA demonstrated the highest hazards ratio for peritoneal recurrence (PMID:31055693)
• Identification SYT13 as a novel biomarker in lung adenocarcinoma. (PMID:31625195)
• Silencing of synaptotagmin 13 inhibits tumor growth through suppressing proliferation and promoting apoptosis of colorectal cancer cells. (PMID:31939613)
• Synaptotagmin 13 is neuroprotective across motor neuron diseases. (PMID:32065260)
• Synaptotagmin 13 Is Highly Expressed in Estrogen Receptor-Positive Breast Cancer. (PMID:34677264)
• The highly expressed calcium-insensitive synaptotagmin-11 and synaptotagmin-13 modulate insulin secretion. (PMID:35753051)
• Role of synaptotagmin 13 (SYT13) in promoting breast cancer and signaling pathways. (PMID:36630025)
• Synaptotagmin 13 Could Drive the Progression of Esophageal Squamous Cell Carcinoma Through Upregulating ACRV1. (PMID:39046915)
• Heterozygous knockout of Synaptotagmin13 phenocopies ALS features and TP53 activation in human motor neurons. (PMID:39097602)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	syt13	ENSDARG00000012306
mus_musculus	Syt13	ENSMUSG00000027220
rattus_norvegicus	Syt13	ENSRNOG00000008000
drosophila_melanogaster	Sytbeta	FBGN0261090

Paralogs (31): SYT7 (ENSG00000011347), 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), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Synaptotagmin-13 — Q7L8C5 (reviewed: Q7L8C5)

Alternative names: Synaptotagmin XIII

All UniProt accessions (3): Q7L8C5, H0YD47, H0YE47

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transport vesicle docking to the plasma membrane.

Subunit / interactions. Interacts with NRXN1.

Subcellular location. Membrane.

Tissue specificity. Expressed in brain, pancreas and kidney.

Domain organisation. The first C2 domain/C2A does not mediate Ca(2+)-dependent phospholipid binding. The second C2 domain/C2B domain binds phospholipids regardless of whether calcium is present.

Similarity. Belongs to the synaptotagmin family.

RefSeq proteins (2): NP_001234916, NP_065877* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR028692	Syt13_C2B	Domain
IPR035892	C2_domain_sf	Homologous_superfamily

Pfam: PF00168

UniProt features (16 total): strand 9, topological domain 2, domain 2, chain 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1WFM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L8C5-F1	69.25	0.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 153 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_REGULATION_OF_VESICLE_FUSION, WHITEHURST_PACLITAXEL_SENSITIVITY, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, MODULE_418, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS

GO Biological Process (4): vesicle-mediated transport (GO:0016192), regulation of calcium ion-dependent exocytosis (GO:0017158), calcium-dependent activation of synaptic vesicle fusion (GO:0099502), regulation of synaptic vesicle exocytosis (GO:2000300)

GO Molecular Function (3): SNARE binding (GO:0000149), calcium-dependent phospholipid binding (GO:0005544), calcium ion sensor activity (GO:0061891)

GO Cellular Component (7): plasma membrane (GO:0005886), transport vesicle (GO:0030133), axon (GO:0030424), synaptic vesicle membrane (GO:0030672), dense core granule (GO:0031045), exocytic vesicle (GO:0070382), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of regulated secretory pathway	2
synaptic vesicle exocytosis	2
transport	1
cellular process	1
calcium-ion regulated exocytosis	1
positive regulation of synaptic vesicle fusion to presynaptic active zone membrane	1
regulation of neurotransmitter secretion	1
protein binding	1
phospholipid binding	1
calcium ion binding	1
metal ion sensor activity	1
membrane	1
cell periphery	1
endomembrane system	1
cytoplasmic vesicle	1
neuron projection	1
synaptic vesicle	1
exocytic vesicle membrane	1
secretory granule	1
transport vesicle	1
secretory vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYT13	NRXN1	Q9ULB1	752
SYT13	SYT1	P21579	518
SYT13	SYT10	Q6XYQ8	472
SYT13	NXPH2	O95156	428
SYT13	VAMP1	P23763	425
SYT13	GRK7	Q8WTQ7	398
SYT13	PDZD11	Q5EBL8	387
SYT13	SYT16	Q17RD7	384
SYT13	EXOC5	O00471	369
SYT13	RAB3C	Q96E17	364
SYT13	UNC13A	Q9UPW8	335
SYT13	KCNK16	Q96T55	333
SYT13	SYT14	Q8NB59	329
SYT13	DISP3	Q9P2K9	326
SYT13	PRDM11	Q9NQV5	321

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SYT13	NCL	psi-mi:“MI:0915”(physical association)	0.400
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYT13	ZDHHC6	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): SYT13 (Proximity Label-MS), SYT13 (Reconstituted Complex), NRXN1 (Reconstituted Complex), FEM1B (Affinity Capture-MS), ZDHHC6 (Affinity Capture-MS), SYT13 (Proximity Label-MS)

ESM2 similar proteins: A0AVI2, A0FGR9, A2AP18, A3KGK3, A6QQP7, F1LYQ8, F8VPU2, O00329, O08835, O14976, O15068, O35904, O75038, O75923, O94887, P19687, P40749, P50232, P58069, P97610, P97874, Q14644, Q15283, Q28013, Q5DTI8, Q5FWL4, Q5M7N9, Q5RAB8, Q5RJH2, Q60790, Q63406, Q63713, Q64096, Q6DN12, Q6P7F1, Q7L8C5, Q7ZWU7, Q8IV01, Q8VHQ7, Q91VS8

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1028 predictions. Top by Δscore:

Variant	Effect	Δscore
11:45244188:T:TA	donor_gain	1.0000
11:45244203:T:TA	donor_gain	1.0000
11:45244352:GACAT:G	acceptor_gain	1.0000
11:45244353:ACAT:A	acceptor_gain	1.0000
11:45244354:CAT:C	acceptor_gain	1.0000
11:45244354:CATC:C	acceptor_gain	1.0000
11:45244357:C:CC	acceptor_gain	1.0000
11:45244358:T:G	acceptor_loss	1.0000
11:45246381:AC:A	donor_gain	1.0000
11:45246382:CC:C	donor_gain	1.0000
11:45252720:CAG:C	acceptor_gain	1.0000
11:45252723:C:CC	acceptor_gain	1.0000
11:45254400:CACAC:C	acceptor_gain	1.0000
11:45254402:CAC:C	acceptor_gain	1.0000
11:45254402:CACCT:C	acceptor_loss	1.0000
11:45254404:CCTGT:C	acceptor_loss	1.0000
11:45254405:C:CC	acceptor_gain	1.0000
11:45254408:T:TC	acceptor_gain	1.0000
11:45255661:CCTA:C	donor_loss	1.0000
11:45255662:CTAC:C	donor_loss	1.0000
11:45255665:CCATT:C	donor_gain	1.0000
11:45255887:TTGAA:T	acceptor_gain	1.0000
11:45255888:TGAA:T	acceptor_gain	1.0000
11:45255889:GAA:G	acceptor_gain	1.0000
11:45255891:ACT:A	acceptor_loss	1.0000
11:45255892:C:CC	acceptor_gain	1.0000
11:45255892:C:CG	acceptor_loss	1.0000
11:45255893:T:G	acceptor_loss	1.0000
11:45286022:CACCT:C	donor_loss	1.0000
11:45286023:ACC:A	donor_loss	1.0000

AlphaMissense

2756 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:45244265:C:A	W356C	1.000
11:45244265:C:G	W356C	1.000
11:45244267:A:G	W356R	1.000
11:45244267:A:T	W356R	1.000
11:45246451:C:G	R303P	1.000
11:45244070:C:A	W421C	0.999
11:45244070:C:G	W421C	0.999
11:45244072:A:G	W421R	0.999
11:45244072:A:T	W421R	0.999
11:45244112:C:A	W407C	0.999
11:45244112:C:G	W407C	0.999
11:45244248:A:G	F362S	0.999
11:45244262:G:C	N357K	0.999
11:45244262:G:T	N357K	0.999
11:45244263:T:A	N357I	0.999
11:45244266:C:G	W356S	0.999
11:45244347:A:T	V329D	0.999
11:45246448:A:G	L304P	0.999
11:45246452:G:T	R303S	0.999
11:45246484:A:G	L292P	0.999
11:45286164:C:T	G15D	0.999
11:45244069:G:C	H422D	0.998
11:45244077:G:T	A419D	0.998
11:45244114:A:G	W407R	0.998
11:45244114:A:T	W407R	0.998
11:45244263:T:G	N357T	0.998
11:45246428:C:G	A311P	0.998
11:45246429:T:A	K310N	0.998
11:45246429:T:G	K310N	0.998
11:45246430:T:A	K310I	0.998

dbSNP variants (sampled 300 via entrez): RS1000008936 (11:45247560 G>A), RS1000096367 (11:45286792 A>T), RS1000148865 (11:45281966 T>C), RS1000183804 (11:45282389 C>T), RS1000315083 (11:45241289 G>T), RS1000398123 (11:45257372 G>A), RS1000613775 (11:45253036 T>C), RS1000664 (11:45264252 T>A,G), RS1000665 (11:45264534 C>G), RS1000678824 (11:45251810 T>G), RS1000680750 (11:45265091 G>A), RS1000746085 (11:45259034 C>A), RS1000749822 (11:45263830 G>C), RS1000798144 (11:45277448 C>T), RS1000832397 (11:45240994 G>A)

Disease associations

OMIM: gene MIM:607716 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002783_399	Body mass index	7.000000e-06
GCST002783_525	Body mass index	7.000000e-06
GCST003880_3	Schizophrenia	1.000000e-06
GCST006193_3	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-09
GCST006194_6	Diastolic blood pressure x smoking status (current vs non-current) interaction (1df test)	1.000000e-08
GCST006412_119	Intraocular pressure	2.000000e-09
GCST006427_33	Depression in smokers	5.000000e-06
GCST007267_67	Systolic blood pressure	5.000000e-10
GCST007269_197	Pulse pressure	6.000000e-15
GCST010988_415	Adult body size	5.000000e-08
GCST90020026_773	Hip index	3.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0004695	intraocular pressure measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
methyleugenol	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Cocaine	affects response to substance	1
Folic Acid	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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