SYT8

Summary

SYT8 (synaptotagmin 8, HGNC:19264) is a protein-coding gene on chromosome 11p15.5, encoding Synaptotagmin-8 (Q8NBV8). Involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues.

This gene encodes a member of the synaptotagmin protein family. Synaptotagmins are membrane proteins that are important in neurotransmission and hormone secretion, both of which involve regulated exocytosis. Expression of the encoded protein in human pancreatic islets has been connected to activity of the promoter for the insulin gene, on the same chromosome several hundred kilobases away (PMID: 21336277 and 22928559). This association would link response to gluclose to insulin secretion. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 90019 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_001394072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19264
Approved symbol	SYT8
Name	synaptotagmin 8
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434K0322
Ensembl gene	ENSG00000149043
Ensembl biotype	protein_coding
OMIM	607719
Entrez	90019

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000341958, ENST00000381968, ENST00000381978, ENST00000417052, ENST00000424556, ENST00000430303, ENST00000464897, ENST00000475245, ENST00000479089, ENST00000479276, ENST00000482118, ENST00000483280, ENST00000490707, ENST00000494431, ENST00000852977, ENST00000852978, ENST00000852979, ENST00000970785, ENST00000970786

RefSeq mRNA: 5 — MANE Select: NM_001394072 NM_001290332, NM_001290333, NM_001290334, NM_001394072, NM_138567

CCDS: CCDS7726, CCDS91401

Canonical transcript exons

ENST00000341958 — 8 exons

Exon	Start	End
ENSE00001490396	1834990	1835199
ENSE00003522967	1836756	1836861
ENSE00003566260	1835296	1835459
ENSE00003569077	1835886	1835984
ENSE00003583767	1836126	1836284
ENSE00003628644	1837192	1837521
ENSE00003643554	1836957	1837090
ENSE00003686259	1836425	1836592

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 94.76.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3015 / max 249.1086, expressed in 227 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112494	0.9966	95
112490	0.7341	155
112493	0.1404	49
112488	0.1179	34
112496	0.0907	36
112495	0.0891	38
112491	0.0556	25
112492	0.0367	20
112489	0.0302	15
112497	0.0101	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	94.76	gold quality
zone of skin	UBERON:0000014	94.43	gold quality
skin of abdomen	UBERON:0001416	94.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.95	gold quality
esophagus mucosa	UBERON:0002469	90.18	gold quality
gall bladder	UBERON:0002110	88.13	gold quality
lower esophagus mucosa	UBERON:0035834	86.92	gold quality
saliva-secreting gland	UBERON:0001044	85.36	gold quality
minor salivary gland	UBERON:0001830	85.07	gold quality
body of pancreas	UBERON:0001150	83.26	gold quality
urinary bladder	UBERON:0001255	82.74	gold quality
placenta	UBERON:0001987	80.18	gold quality
right lung	UBERON:0002167	75.92	gold quality
upper lobe of left lung	UBERON:0008952	74.81	gold quality
pancreas	UBERON:0001264	72.58	gold quality
right uterine tube	UBERON:0001302	71.45	gold quality
duodenum	UBERON:0002114	70.92	gold quality
tonsil	UBERON:0002372	69.99	gold quality
ascending aorta	UBERON:0001496	69.67	gold quality
thoracic aorta	UBERON:0001515	69.44	gold quality
lung	UBERON:0002048	69.02	gold quality
vagina	UBERON:0000996	68.29	gold quality
esophagus	UBERON:0001043	67.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.37	gold quality
mucosa of stomach	UBERON:0001199	66.84	gold quality
small intestine	UBERON:0002108	66.46	gold quality
descending thoracic aorta	UBERON:0002345	66.10	gold quality
right coronary artery	UBERON:0001625	65.82	gold quality
thoracic mammary gland	UBERON:0005200	64.88	gold quality
left coronary artery	UBERON:0001626	64.79	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	108.79
E-MTAB-6678	yes	16.16
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

Literature-anchored findings (GeneRIF, showing 2)

• Inactivation of the insulin promoter by promoter-targeting siRNA reduces SYT8 gene expression. (PMID:21336277)
• SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC. (PMID:28026832)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Syt8	ENSMUSG00000031098
rattus_norvegicus	Syt8	ENSRNOG00000020245

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), 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-8 — Q8NBV8 (reviewed: Q8NBV8)

Alternative names: Synaptotagmin VIII

All UniProt accessions (6): Q8NBV8, A0AA75HZC2, C9J253, C9K032, F8WBL4, H0Y3G9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Mediates Ca(2+)-regulation of exocytosis acrosomal reaction in sperm. May mediate Ca(2+)-regulation of exocytosis in insulin secreted cells.

Subunit / interactions. Homodimer or homooligomer. Homodimerization and homooligomerization do not depend on Ca(2+). Interacts with SYNCRIP isoform 2 C-terminus. Binds inositol 1,3,4,5-tetrakisphosphate (IP4). Binds to AP2 in a Ca(2+)-independent manner. Interacts with STX1A, STX1B and STX2; the interaction is Ca(2+)-dependent.

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

Domain organisation. The first C2 domain/C2A does not mediate Ca(2+)-dependent phospholipid binding. The second C2 domain/C2B is responsible for SYNCRIP and inositol 1,3,4,5-tetrakisphosphate (IP4)-binding.

Similarity. Belongs to the synaptotagmin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NBV8-4	4	yes
Q8NBV8-1	1

RefSeq proteins (5): NP_001277261, NP_001277262, NP_001277263, NP_001381001, NP_612634 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00168

UniProt features (18 total): sequence variant 5, sequence conflict 4, topological domain 2, domain 2, splice variant 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-Q8NBV8-F1	80.61	0.54

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 141 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RNGTGGGC_UNKNOWN, GOBP_SINGLE_FERTILIZATION, GOBP_REGULATION_OF_VESICLE_FUSION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, MODULE_418, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_CELL_CELL_SIGNALING

GO Biological Process (5): acrosome reaction (GO:0007340), 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 (4): SNARE binding (GO:0000149), calcium-dependent phospholipid binding (GO:0005544), calcium-dependent protein binding (GO:0048306), calcium ion sensor activity (GO:0061891)

GO Cellular Component (10): acrosomal vesicle (GO:0001669), plasma membrane (GO:0005886), axon (GO:0030424), synaptic vesicle membrane (GO:0030672), dense core granule (GO:0031045), exocytic vesicle (GO:0070382), cytoplasm (GO:0005737), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of regulated secretory pathway	2
synaptic vesicle exocytosis	2
protein binding	2
calcium ion binding	2
secretory granule	2
cellular anatomical structure	2
membrane fusion involved in acrosome reaction	1
single fertilization	1
reproductive process	1
acrosomal vesicle exocytosis	1
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
phospholipid binding	1
metal ion sensor activity	1
membrane	1
cell periphery	1
neuron projection	1
synaptic vesicle	1
exocytic vesicle membrane	1
transport vesicle	1
secretory vesicle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1
membrane-bounded organelle	1

Protein interactions and networks

STRING

490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYT8	MRPL23	Q16540	558
SYT8	STX2	P32856	541
SYT8	SYT3	Q9BQG1	471
SYT8	STX11	O75558	456
SYT8	KLHL14	Q9P2G3	440
SYT8	TNNI2	P48788	437
SYT8	ANO1	Q5XXA6	422
SYT8	VAMP5	O95183	420
SYT8	A8MYK1	A8MYK1	416
SYT8	STX18	Q9P2W9	415
SYT8	RAB3D	O95716	405
SYT8	SERF2	P84101	384
SYT8	STK3	Q13188	376
SYT8	TLDC2	A0PJX2	370
SYT8	GLP1R	P43220	364

IntAct

0 interactions, top by confidence:

BioGRID (2): SYNCRIP (Reconstituted Complex), SYT8 (Affinity Capture-Western)

ESM2 similar proteins: D3YZZ2, E7ERA6, F2Z333, H3BV60, O00292, O18796, O43508, O43612, O54907, O55232, O55241, O60391, O75462, O75610, O77668, O95633, O95685, P13224, P41155, P56717, Q02833, Q06643, Q14626, Q1LZB9, Q2TBM7, Q4V892, Q5RF19, Q5TM22, Q6IA17, Q6UXT9, Q6ZMM2, Q862Z7, Q86VR8, Q86YD3, Q8BQB4, Q8NBV8, Q8TAD2, Q99640, Q99MF4, Q9BZR6

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1383 predictions. Top by Δscore:

Variant	Effect	Δscore
11:1835982:G:GT	donor_gain	1.0000
11:1836006:G:GT	donor_gain	1.0000
11:1836031:A:T	donor_gain	1.0000
11:1836045:G:GT	donor_gain	1.0000
11:1836045:G:T	donor_gain	1.0000
11:1836285:G:GG	donor_gain	1.0000
11:1836589:TCAG:T	donor_loss	1.0000
11:1836590:CAG:C	donor_loss	1.0000
11:1836591:AG:A	donor_loss	1.0000
11:1836592:GG:G	donor_loss	1.0000
11:1836754:A:AG	acceptor_gain	1.0000
11:1836755:G:GG	acceptor_gain	1.0000
11:1836755:GC:G	acceptor_gain	1.0000
11:1836755:GCCC:G	acceptor_gain	1.0000
11:1836955:A:AG	acceptor_gain	1.0000
11:1836956:G:GG	acceptor_gain	1.0000
11:1835393:G:GT	donor_gain	0.9900
11:1835879:A:AG	acceptor_gain	0.9900
11:1835880:C:G	acceptor_gain	0.9900
11:1835881:TCCA:T	acceptor_loss	0.9900
11:1835882:CCAG:C	acceptor_loss	0.9900
11:1835883:CAGGT:C	acceptor_loss	0.9900
11:1835884:A:AG	acceptor_gain	0.9900
11:1835884:AGGT:A	acceptor_gain	0.9900
11:1835885:G:GG	acceptor_gain	0.9900
11:1835885:GGT:G	acceptor_gain	0.9900
11:1835885:GGTG:G	acceptor_gain	0.9900
11:1835974:G:GT	donor_gain	0.9900
11:1836030:G:GT	donor_gain	0.9900
11:1836034:GG:G	donor_gain	0.9900

AlphaMissense

2459 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:1837064:T:C	F314L	0.972
11:1837066:C:A	F314L	0.972
11:1837066:C:G	F314L	0.972
11:1836261:T:C	F179L	0.962
11:1836263:T:A	F179L	0.962
11:1836263:T:G	F179L	0.962
11:1837058:T:C	F312L	0.949
11:1837060:C:A	F312L	0.949
11:1837060:C:G	F312L	0.949
11:1837046:T:C	F308L	0.948
11:1837048:C:A	F308L	0.948
11:1837048:C:G	F308L	0.948
11:1836262:T:G	F179C	0.930
11:1837065:T:C	F314S	0.916
11:1837302:G:C	W359C	0.913
11:1837302:G:T	W359C	0.913
11:1836279:T:C	F185L	0.910
11:1836281:C:A	F185L	0.910
11:1836281:C:G	F185L	0.910
11:1836970:G:C	K282N	0.897
11:1836970:G:T	K282N	0.897
11:1837065:T:G	F314C	0.886
11:1837050:A:T	N309I	0.882
11:1836187:C:A	A154D	0.881
11:1836127:T:C	I134T	0.878
11:1836820:T:A	V264E	0.878
11:1836826:T:A	V266E	0.876
11:1836966:T:A	V281E	0.875
11:1837047:T:C	F308S	0.875
11:1836476:T:C	F204L	0.872

dbSNP variants (sampled 300 via entrez): RS1000366025 (11:1837915 G>A), RS1000539869 (11:1830948 G>A), RS1000614662 (11:1830086 C>A,T), RS1000930347 (11:1831101 A>G), RS1001406518 (11:1837553 C>T), RS1001466986 (11:1837666 G>A,C), RS1001490265 (11:1834177 C>A), RS1001527733 (11:1834187 C>T), RS1001654008 (11:1830028 G>A), RS1001791389 (11:1830808 A>G), RS1001978632 (11:1834009 G>A), RS1002002715 (11:1830747 C>T), RS1002945694 (11:1833206 C>A,T), RS1003748293 (11:1836784 C>G,T), RS1003987662 (11:1830602 C>G)

Disease associations

OMIM: gene MIM:607719 | 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
GCST002112_1	Celiac disease	7.000000e-06
GCST007000_5	Logical memory (delayed recall) in mild cognitive impairment	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects methylation, decreases expression, increases abundance	5
Particulate Matter	increases expression, decreases expression, increases abundance, affects cotreatment	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
bisphenol F	decreases expression	1
propylparaben	decreases expression	1
bisphenol A	decreases expression	1
lead acetate	decreases expression	1
methylparaben	decreases expression	1
butyraldehyde	increases expression	1
cupric chloride	decreases expression	1
perfluorodecanoic acid	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Calcitriol	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Mercuric Chloride	increases expression	1
Phenobarbital	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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