SYT12

Summary

SYT12 (synaptotagmin 12, HGNC:18381) is a protein-coding gene on chromosome 11q13.2, encoding Synaptotagmin-12 (Q8IV01). Synaptic vesicle phosphoprotein that enhances spontaneous neurotransmitter release but does not effect induced neurotransmitter release.

This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. Studies of the orthologous gene in rat have shown that the encoded protein selectively modulates spontaneous synaptic-vesicle exocytosis and may also be involved in regulating calcium independent secretion in nonneuronal cells. Alternative splicing results in multiple transcript variants. The gene has previously been referred to as synaptotagmin XI but has been renamed synaptotagmin XII to be standard with mouse and rat official nomenclature.

Source: NCBI Gene 91683 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_177963

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18381
Approved symbol	SYT12
Name	synaptotagmin 12
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	SRG1
Ensembl gene	ENSG00000173227
Ensembl biotype	protein_coding
OMIM	606436
Entrez	91683

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000393946, ENST00000525149, ENST00000525457, ENST00000526281, ENST00000527043, ENST00000531392, ENST00000533427, ENST00000891866, ENST00000932787, ENST00000932788, ENST00000932789, ENST00000932790, ENST00000945332, ENST00000945333, ENST00000945334, ENST00000945335

RefSeq mRNA: 4 — MANE Select: NM_177963 NM_001177880, NM_001318773, NM_001318775, NM_177963

CCDS: CCDS8154

Canonical transcript exons

ENST00000527043 — 8 exons

Exon	Start	End
ENSE00001187059	67045744	67045877
ENSE00001187065	67044593	67044713
ENSE00001187072	67043638	67043853
ENSE00001187080	67039811	67040203
ENSE00001516979	67048584	67050863
ENSE00002168244	67023134	67023460
ENSE00003518786	67034645	67034838
ENSE00003657668	67030122	67030178

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 92.92.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3977 / max 52.3008, expressed in 404 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115384	1.0213	265
115387	0.4360	195
115385	0.3935	154
115388	0.2309	138
115386	0.1814	120
206348	0.1345	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	92.92	gold quality
cerebellar cortex	UBERON:0002129	92.85	gold quality
cerebellar hemisphere	UBERON:0002245	92.80	gold quality
cerebellum	UBERON:0002037	91.68	gold quality
cerebellar vermis	UBERON:0004720	89.52	gold quality
prefrontal cortex	UBERON:0000451	87.95	gold quality
right frontal lobe	UBERON:0002810	87.19	gold quality
frontal cortex	UBERON:0001870	85.57	gold quality
anterior cingulate cortex	UBERON:0009835	84.90	gold quality
cingulate cortex	UBERON:0003027	84.85	gold quality
neocortex	UBERON:0001950	84.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.64	gold quality
postcentral gyrus	UBERON:0002581	82.50	gold quality
parietal lobe	UBERON:0001872	81.90	gold quality
pons	UBERON:0000988	81.62	gold quality
nucleus accumbens	UBERON:0001882	81.57	gold quality
cerebral cortex	UBERON:0000956	81.47	gold quality
superior frontal gyrus	UBERON:0002661	80.77	gold quality
right coronary artery	UBERON:0001625	80.72	gold quality
putamen	UBERON:0001874	80.67	gold quality
telencephalon	UBERON:0001893	80.48	gold quality
brain	UBERON:0000955	79.86	gold quality
caudate nucleus	UBERON:0001873	79.85	gold quality
right lobe of liver	UBERON:0001114	79.41	gold quality
forebrain	UBERON:0001890	79.25	gold quality
pancreatic ductal cell	CL:0002079	78.77	silver quality
primary visual cortex	UBERON:0002436	77.66	gold quality
corpus epididymis	UBERON:0004359	77.49	gold quality
decidua	UBERON:0002450	76.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting SYT12, 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-4481	100.00	66.42	1669
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4758-3P	99.12	63.96	869

Literature-anchored findings (GeneRIF, showing 2)

• Studies of the orthologous gene in rat have shown that spontaneous synaptic-vesicle exocytosis is selectively modulated by synaptotagmin 12. (PMID:17190793)
• Synaptotagmin 12 (SYT12) Gene Expression Promotes Cell Proliferation and Progression of Lung Adenocarcinoma and Involves the Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway. (PMID:32108133)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	syt12	ENSDARG00000101776
mus_musculus	Syt12	ENSMUSG00000049303
rattus_norvegicus	Syt12	ENSRNOG00000019306
drosophila_melanogaster	Syt12	FBGN0261085
caenorhabditis_elegans		WBGENE00004925

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), RPH3AL (ENSG00000181031), C2CD4C (ENSG00000183186), C2CD4A (ENSG00000198535), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Synaptotagmin-12 — Q8IV01 (reviewed: Q8IV01)

Alternative names: Synaptotagmin XII

All UniProt accessions (2): Q8IV01, E9PNM5

UniProt curated annotations — full annotation on UniProt →

Function. Synaptic vesicle phosphoprotein that enhances spontaneous neurotransmitter release but does not effect induced neurotransmitter release. Unlike other synaptotagmins, it does not bind Ca(2+) or phospholipids. Essential for mossy-fiber long-term potentiation in the hippocampus.

Subunit / interactions. Homodimer. Can also form heterodimers. Interacts with SYT1.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Post-translational modifications. Phosphorylation of Ser-97 is required for mossy-fiber long-term potentiation.

Similarity. Belongs to the synaptotagmin family.

RefSeq proteins (4): NP_001171351, NP_001305702, NP_001305704, NP_808878* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR030537	Syt12_C2B	Domain
IPR035892	C2_domain_sf	Homologous_superfamily

Pfam: PF00168

UniProt features (10 total): modified residue 3, topological domain 2, domain 2, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IV01-F1	74.47	0.28

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 (3): 97, 99, 214

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 149 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, AHRARNT_01, BENPORATH_ES_WITH_H3K27ME3, TGCGCANK_UNKNOWN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, chr11q13, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_EXOCYTOSIS, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_SECRETION

GO Biological Process (5): vesicle-mediated transport (GO:0016192), regulation of calcium ion-dependent exocytosis (GO:0017158), spontaneous exocytosis of neurotransmitter (GO:0048792), long-term synaptic potentiation (GO:0060291), presynaptic modulation of chemical synaptic transmission (GO:0099171)

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

GO Cellular Component (9): plasma membrane (GO:0005886), synaptic vesicle membrane (GO:0030672), exocytic vesicle (GO:0070382), hippocampal mossy fiber to CA3 synapse (GO:0098686), synaptic vesicle (GO:0008021), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
presynapse	2
cellular anatomical structure	2
transport	1
cellular process	1
calcium-ion regulated exocytosis	1
regulation of regulated secretory pathway	1
neurotransmitter secretion	1
synaptic vesicle exocytosis	1
regulation of synaptic plasticity	1
positive regulation of synaptic transmission	1
modulation of chemical synaptic transmission	1
protein binding	1
phospholipid binding	1
calcium ion binding	1
metal ion sensor activity	1
membrane	1
cell periphery	1
synaptic vesicle	1
exocytic vesicle membrane	1
transport vesicle	1
secretory vesicle	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1
exocytic vesicle	1
cytoplasm	1
intracellular vesicle	1
cell junction	1
synapse	1

Protein interactions and networks

STRING

874 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYT12	CCDC62	Q6P9F0	720
SYT12	ACMSD	Q8TDX5	668
SYT12	MCCC1	Q96RQ3	663
SYT12	STX1B	P61266	633
SYT12	GAK	O14976	604
SYT12	HIP1R	O75146	596
SYT12	STK39	Q9UEW8	593
SYT12	SYT1	P21579	542
SYT12	RIT2	Q99578	508
SYT12	LRRK2	Q5S007	507
SYT12	DGKQ	P52824	481
SYT12	GBA1	P04062	479
SYT12	SYN2	Q92777	477
SYT12	SNCA	P37840	474
SYT12	TMEM175	Q9BSA9	471

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MAPK8	WDR62	psi-mi:“MI:0914”(association)	0.730
SYT12	B4GALT5	psi-mi:“MI:0914”(association)	0.530
SYT12	PDK2	psi-mi:“MI:0914”(association)	0.530
CFTR	SYT12	psi-mi:“MI:0915”(physical association)	0.370
PIM1	IDH3B	psi-mi:“MI:0914”(association)	0.350
SYT12	APOD	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): SYT12 (Affinity Capture-RNA), SYT12 (Affinity Capture-RNA), SYT12 (Affinity Capture-RNA), PDK2 (Affinity Capture-MS), GMCL1 (Affinity Capture-MS), HTT (Affinity Capture-MS), PDK3 (Affinity Capture-MS), MADD (Affinity Capture-MS), CCDC77 (Affinity Capture-MS), ENTPD7 (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), ZNF445 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), B4GALT5 (Affinity Capture-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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1785 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67021861:T:TA	acceptor_gain	1.0000
11:67021864:TCCA:T	acceptor_loss	1.0000
11:67021865:CCA:C	acceptor_loss	1.0000
11:67021866:CA:C	acceptor_loss	1.0000
11:67021867:A:AG	acceptor_gain	1.0000
11:67021868:G:C	acceptor_loss	1.0000
11:67021868:G:GG	acceptor_gain	1.0000
11:67021911:AAG:A	donor_gain	1.0000
11:67021911:AAGG:A	donor_loss	1.0000
11:67021914:G:GG	donor_gain	1.0000
11:67021915:T:G	donor_loss	1.0000
11:67030522:TC:T	donor_gain	1.0000
11:67040199:CTCGG:C	donor_gain	1.0000
11:67040200:TCGG:T	donor_gain	1.0000
11:67040201:CGG:C	donor_gain	1.0000
11:67040201:CGGGT:C	donor_loss	1.0000
11:67040202:GG:G	donor_gain	1.0000
11:67040202:GGG:G	donor_gain	1.0000
11:67040202:GGGTA:G	donor_loss	1.0000
11:67040203:GG:G	donor_gain	1.0000
11:67040203:GGTA:G	donor_loss	1.0000
11:67040204:G:GG	donor_gain	1.0000
11:67040204:GT:G	donor_loss	1.0000
11:67040205:T:A	donor_loss	1.0000
11:67043633:TGCA:T	acceptor_loss	1.0000
11:67043634:GCAGA:G	acceptor_loss	1.0000
11:67043635:CAG:C	acceptor_loss	1.0000
11:67043636:A:AG	acceptor_gain	1.0000
11:67043636:A:T	acceptor_loss	1.0000
11:67043637:G:GG	acceptor_gain	1.0000

AlphaMissense

2767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67044632:T:G	Y293D	1.000
11:67044636:T:C	L294P	1.000
11:67044651:G:C	R299P	1.000
11:67044654:T:C	L300P	1.000
11:67045753:T:A	V323D	1.000
11:67045793:A:C	K336N	1.000
11:67045793:A:T	K336N	1.000
11:67045852:T:C	F356S	1.000
11:67048660:G:A	G390E	1.000
11:67048692:T:A	W401R	1.000
11:67048692:T:C	W401R	1.000
11:67044608:G:T	G285W	0.999
11:67044618:T:C	L288P	0.999
11:67044621:T:C	L289P	0.999
11:67044623:T:C	S290P	0.999
11:67044627:T:A	L291H	0.999
11:67044627:T:C	L291P	0.999
11:67044645:C:A	A297D	0.999
11:67044650:C:A	R299S	0.999
11:67044654:T:A	L300H	0.999
11:67044660:T:A	V302E	0.999
11:67045755:A:G	K324E	0.999
11:67045757:G:C	K324N	0.999
11:67045757:G:T	K324N	0.999
11:67045759:T:A	V325E	0.999
11:67045765:T:C	L327P	0.999
11:67045768:T:C	L328P	0.999
11:67045791:A:G	K336E	0.999
11:67045792:A:T	K336I	0.999
11:67045833:T:C	F350L	0.999

dbSNP variants (sampled 300 via entrez): RS1000099727 (11:67043429 G>A,C), RS1000106164 (11:67032161 G>A), RS1000129453 (11:67027878 G>A), RS1000133615 (11:67017472 G>A,T), RS1000183626 (11:67027679 GC>G,GCC), RS1000217066 (11:67040320 A>G,T), RS1000273729 (11:67033513 C>T), RS1000335080 (11:67005312 G>A), RS1000405248 (11:67005517 G>A), RS1000408583 (11:67034053 A>T), RS1000415982 (11:67015762 A>T), RS1000464730 (11:67017287 G>A,C,T), RS1000466937 (11:67015523 G>A), RS1000498622 (11:67029115 C>T), RS1000727943 (11:67023301 C>A,G,T)

Disease associations

OMIM: gene MIM:606436 | 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
GCST001241_12	Bipolar disorder	2.000000e-07
GCST90020029_341	Waist circumference adjusted for body mass index	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	4
Tetrachlorodibenzodioxin	increases expression, affects binding, increases reaction	3
sodium arsenite	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Calcitriol	increases expression	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
abrine	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	affects methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	increases expression	1
Lead	affects expression	1

Clinical trials (associated diseases)

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