SYT2 Gene

HGNC Family	C2 domain containing
Name	synaptotagmin II
Description	This gene encodes a synaptic vesicle membrane protein. The encoded protein is thought to function as a calcium sensor in vesicular trafficking and exocytosis. Mutations in this gene are associated with myasthenic syndrome, presynaptic, congenital, with or without motor neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSynaptotagmin‐2 (SYT2) is a pivotal membrane protein that serves as the principal Ca²⁺ sensor in fast, synchronous neurotransmitter release at presynaptic terminals, particularly at neuromuscular junctions. Through its tandem C2 domains, SYT2 binds to the syntaxin/SNAP‑25 t‐SNARE complex in a calcium‐dependent manner to up‐regulate the probability of synaptic vesicle fusion. Disruption of these interactions—as evidenced by mutations in the conserved C2B domain—undermines vesicle priming and coupling with Ca²⁺ channels, leading to presynaptic congenital myasthenic syndromes and motor neuropathies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in exocytosis, SYT2 function is modulated by post‑translational modifications and interactions with other molecules. Phosphorylation by kinases such as WNK1 alters the Ca²⁺ affinity of its C2 domains, effectively fine‑tuning vesicle release in response to cellular signals. Moreover, SYT2 acts as a receptor for certain botulinum neurotoxins (e.g., BoNT/B, BoNT/D-C, and BoNT/G), whereby its luminal domain mediates the binding and neuronal entry of these toxins—a property that also exhibits species‑specific nuances influencing toxin potency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInterestingly, SYT2’s roles are not confined to the nervous system. In human neutrophils, SYT2 localizes to specific granules and translocates to the plasma membrane and phagosomes upon stimulation, suggesting that it may function as a Ca²⁺ sensor for exocytosis and membrane fusion in immune cells as well."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Colin Rickman, Deborah A Archer, Frederic A Meunier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M310710200"}], "href": "https://doi.org/10.1074/jbc.M310710200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14709554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14709554"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Samuel M Young, Erwin Neher "}, {"type": "b", "children": [{"type": "t", "text": "Synaptotagmin has an essential function in synaptic vesicle positioning for synchronous release in addition to its role as a calcium sensor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2009.07.028"}], "href": "https://doi.org/10.1016/j.neuron.2009.07.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19709630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19709630"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David N Herrmann, Rita Horvath, Janet E Sowden, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2014.08.007"}], "href": "https://doi.org/10.1016/j.ajhg.2014.08.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25192047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25192047"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Roger G Whittaker, David N Herrmann, Boglarka Bansagi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000002185"}], "href": "https://doi.org/10.1212/WNL.0000000000002185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26519543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26519543"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ricardo A Maselli, Hélio van der Linden, Michael Ferns "}, {"type": "b", "children": [{"type": "t", "text": "Recessive congenital myasthenic syndrome caused by a homozygous mutation in SYT2 altering a highly conserved C-terminal amino acid sequence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61579"}], "href": "https://doi.org/10.1002/ajmg.a.61579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32250532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32250532"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sandra Donkervoort, Payam Mohassel, Lucia Laugwitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61765"}], "href": "https://doi.org/10.1002/ajmg.a.61765"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32776697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32776697"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Olga Mironovich, Elena Dadali, Sergey Malmberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a Novel "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "de Novo"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Variant in the "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SYT2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Gene Causing a Rare Type of Distal Hereditary Motor Neuropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes11111238"}], "href": "https://doi.org/10.3390/genes11111238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33105646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33105646"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Byung-Hoon Lee, Xiaoshan Min, Charles J Heise, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2004.07.018"}], "href": "https://doi.org/10.1016/j.molcel.2004.07.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15350218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15350218"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jing Shi, Shizhong Bao, Jun Yin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dominant antigenic peptides located at the heavy chain terminal of botulinum neurotoxin B contain receptor-binding sites for synaptotagmin II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.07.048"}], "href": "https://doi.org/10.1016/j.bbrc.2008.07.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18639519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18639519"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jasmin Strotmeier, Gesche Willjes, Thomas Binz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human synaptotagmin-II is not a high affinity receptor for botulinum neurotoxin B and G: increased therapeutic dosage and immunogenicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2011.12.037"}], "href": "https://doi.org/10.1016/j.febslet.2011.12.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22265973"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22265973"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Lisheng Peng, Ronnie P-A Berntsson, William H Tepp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human synaptotagmin II is not an effective receptor for type B, D-C and G toxins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.103564"}], "href": "https://doi.org/10.1242/jcs.103564"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22454523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22454523"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "I Maria Lindmark, Anna Karlsson, Lena Serrander, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synaptotagmin II could confer Ca(2+) sensitivity to phagocytosis in human neutrophils."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0167-4889(02)00209-4"}], "href": "https://doi.org/10.1016/s0167-4889(02"}, {"type": "t", "text": "00209-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12063179"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12063179"}]}]}]}
Synonyms	MYSPC, SYTII, CMS7
Proteins	SYT2_HUMAN
NCBI Gene ID	127833
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SYT2 has 4,913 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 121 datasets.

Click the + buttons to view associations for SYT2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SYT2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SYT2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SYT2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SYT2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SYT2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SYT2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SYT2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SYT2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SYT2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SYT2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SYT2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SYT2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SYT2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SYT2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SYT2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SYT2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with SYT2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SYT2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SYT2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SYT2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SYT2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SYT2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SYT2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SYT2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SYT2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SYT2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SYT2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SYT2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SYT2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SYT2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SYT2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SYT2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SYT2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SYT2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SYT2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SYT2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SYT2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SYT2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SYT2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SYT2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SYT2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.