Details for: SYT2

Gene ID: 127833

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SYT2

Ensembl ID: ENSG00000143858

Description: synaptotagmin 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • retinal ganglion cell CL0000740
    CSI 8.04
    rCSI 17.75%
    PRS 94.92
  • cerebral cortex neuron CL0010012
    CSI 6.82
    rCSI 27.79%
    PRS 94.95
  • cerebellar granule cell CL0001031
    CSI 5.36
    rCSI 7.88%
    PRS 96.26
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 4.78
    rCSI 17.19%
    PRS 94.17
  • regular atrial cardiac myocyte CL0002129
    CSI 4.59
    rCSI 14.76%
    PRS 96.58
  • adipocyte CL0000136
    CSI 4.37
    rCSI 5.61%
    PRS 95.76
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.86
    rCSI 4.61%
    PRS 95.08
  • inhibitory interneuron CL0000498
    CSI 3.62
    rCSI 8.36%
    PRS 95.35
  • retinal bipolar neuron CL0000748
    CSI 3.59
    rCSI 6.73%
    PRS 95.63
  • hepatic stellate cell CL0000632
    CSI 3.35
    rCSI 12.56%
    PRS 97.56
  • cardiac muscle cell CL0000746
    CSI 3.31
    rCSI 4.75%
    PRS 95.26
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.23
    rCSI 4.02%
    PRS 94.31
  • parietal epithelial cell CL1000452
    CSI 2.56
    rCSI 6.84%
    PRS 97.41
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.07
    rCSI 3.66%
    PRS 95.08
  • cerebellar neuron CL1001611
    CSI 1.9
    rCSI 16.73%
    PRS 92.65
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.71
    rCSI 2.75%
    PRS 95.03
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.55
    rCSI 4.85%
    PRS 95.69
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.52
    rCSI 3.7%
    PRS 93.87
  • basket cell CL0000118
    CSI 1.5
    rCSI 9.4%
    PRS 88.82
  • ON midget ganglion cell CL4033046
    CSI 1.42
    rCSI 28.89%
    PRS 94.49
  • OFF midget ganglion cell CL4033047
    CSI 1.39
    rCSI 28.37%
    PRS 94.56
  • direct pathway medium spiny neuron CL4023026
    CSI 1.28
    rCSI 30.64%
    PRS 93.11
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.28
    rCSI 30.78%
    PRS 92.75
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.13
    rCSI 7.05%
    PRS 95.82
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.1
    rCSI 4.14%
    PRS 94.67
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.91
    rCSI 5.36%
    PRS 94.84
  • ON parasol ganglion cell CL4033052
    CSI 0.81
    rCSI 11.5%
    PRS 94.59
  • central nervous system neuron CL2000029
    CSI 0.58
    rCSI 4.27%
    PRS 95.72

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SYT2](/details-gene/127833) (synaptotagmin 2) encodes a synaptic vesicle membrane protein that acts as a primary calcium sensor for the rapid, synchronous exocytosis of neurotransmitters and hormones. As a member of the synaptotagmin family, its function is critical for coupling action potentials to vesicle fusion at the presynaptic terminal. **Overall**, expression data reveals that [SYT2](/details-gene/127833) is a defining marker for a variety of neuronal subtypes, with the highest significance observed in [retinal ganglion cell](/details-cell/CL0000740)s, [cerebral cortex neuron](/details-cell/CL0010012)s, and [cerebellar granule cell](/details-cell/CL0001031)s. Clinically, mutations in [SYT2](/details-gene/127833) are directly implicated in both dominant and recessive forms of congenital myasthenic syndromes, highlighting its indispensable role at the neuromuscular junction ([Link](https://omim.org/entry/600104)). ## Cellular Roles and Expression Landscape The expression profile of [SYT2](/details-gene/127833) firmly establishes it as a key component of the nervous system. **Overall**, its significance is highest in diverse neuronal populations, including excitatory glutamatergic neurons such as [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041)s and inhibitory interneurons like [VIP GABAergic cortical interneuron](/details-cell/CL4023016)s. This broad expression across different neuronal types underscores its fundamental role in mediating synaptic transmission throughout the central nervous system. Beyond the brain and retina, [SYT2](/details-gene/127833) shows significant expression in other excitable cells, such as [regular atrial cardiac myocyte](/details-cell/CL0002129)s and the broader [cardiac muscle cell](/details-cell/CL0000746) population. This suggests a potential role in regulating calcium-dependent secretion or membrane trafficking events in the heart. Interestingly, the gene also demonstrates notable significance in non-neuronal, non-muscle cells, including [adipocyte](/details-cell/CL0000136)s and [hepatic stellate cell](/details-cell/CL0000632)s, hinting at a more widespread, albeit less characterized, function in vesicle-mediated transport processes outside of classical synaptic contexts. ## Pathways and Molecular Function The molecular function of [SYT2](/details-gene/127833) is centered on its role as a calcium sensor and its interactions with the synaptic machinery. Gene Ontology annotations confirm its involvement in 'Calcium-dependent activation of synaptic vesicle fusion' ([GO:0099502](https://www.ebi.ac.uk/QuickGO/term/GO:0099502)) and 'Regulation of synaptic vesicle exocytosis' ([GO:2000300](https://www.ebi.ac.uk/QuickGO/term/GO:2000300)). This is achieved through its 'Calcium ion sensor activity' ([GO:0061891](https://www.ebi.ac.uk/QuickGO/term/GO:0061891)) and 'Snare binding' ([GO:0000149](https://www.ebi.ac.uk/QuickGO/term/GO:0000149)) capabilities, allowing it to trigger the fusion of the [synaptic vesicle membrane](/details-cell/GO0030672) with the presynaptic [plasma membrane](/details-cell/GO0005886). Reactome pathway analysis further situates [SYT2](/details-gene/127833) within the core 'Neuronal system' ([R-HSA-112316](https://reactome.org/content/detail/R-HSA-112316)) and highlights its participation in 'Protein-protein interactions at synapses' ([R-HSA-6794362](https://reactome.org/content/detail/R-HSA-6794362)). Its annotation in pathways related to 'Clathrin-mediated endocytosis' ([R-HSA-8856828](https://reactome.org/content/detail/R-HSA-8856828)) is consistent with its role in the synaptic vesicle cycle, which involves both exocytosis and subsequent membrane recycling. Notably, its inclusion in pathways like 'Neurotoxicity of clostridium toxins' ([R-HSA-168799](https://reactome.org/content/detail/R-HSA-168799)) underscores its importance as a molecular target for bacterial toxins that disrupt neurotransmission. ## Research Directions The established role of [SYT2](/details-gene/127833) in congenital myasthenic syndromes confirms its critical function at the neuromuscular junction ([Link](https://doi.org/10.1016/j.ajhg.2014.08.007), [Link](https://doi.org/10.1002/ajmg.a.61579)). However, its significant expression in other tissues, such as cardiac muscle and adipose tissue, opens new avenues for investigation into potential extra-neurological functions and disease contributions. **Proposed Hypotheses:** 1. Given its expression in [cardiac muscle cell](/details-cell/CL0000746)s and its function as a calcium sensor for exocytosis, disease-causing mutations in [SYT2](/details-gene/127833) may predispose individuals to cardiac dysfunction. It is hypothesized that pathogenic variants impair the regulated secretion of autocrine/paracrine factors (e.g., natriuretic peptides) from cardiomyocytes, contributing to subtle defects in cardiac signaling or stress responses that are currently unrecognized. 2. The significant expression of [SYT2](/details-gene/127833) in [adipocyte](/details-cell/CL0000136)s suggests it may regulate the calcium-dependent secretion of adipokines. It is hypothesized that [SYT2](/details-gene/127833) is a key component of the exocytotic machinery for hormones like leptin and adiponectin, and that variation in its expression or function could influence systemic metabolic homeostasis. **Experimental Approach:** To test the hypothesis regarding its role in adipocyte function, one could utilize CRISPR-Cas9 to knock out [SYT2](/details-gene/127833) in a human preadipocyte cell line. After differentiation into mature [adipocyte](/details-cell/CL0000136)s, these knockout cells and their wild-type counterparts would be stimulated with secretagogues (e.g., insulin, isoproterenol). The secretion of leptin and adiponectin into the media would be quantified by ELISA. A significant reduction in stimulated, but not basal, secretion in the knockout cells would support a role for [SYT2](/details-gene/127833) in the regulated exocytosis of adipokines. **Therapeutic Potential:** As [SYT2](/details-gene/127833)-related pathologies are predominantly loss-of-function congenital myasthenic syndromes, therapeutic strategies should focus on **activation** or gene replacement rather than inhibition. The specificity of the phenotype to the neuromuscular junction suggests that a targeted gene therapy approach, perhaps using adeno-associated virus (AAV) vectors with muscle-specific promoters to deliver a functional copy of the [SYT2](/details-gene/127833) gene, could be a viable long-term strategy. Such an approach would aim to restore proper presynaptic function and alleviate the myasthenic symptoms experienced by patients.

Genular Protein ID: 1315739470

Symbol: SYT2_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8N9I0 Q496K5 Q8NBE5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CTD 1 ChEBI 19 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 ELM 1 EMBL 5 Ensembl 2 GO 17 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 4 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11381094

Title: Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery.

PubMed ID: 11381094

DOI: 10.1083/jcb.153.5.1111

PubMed ID: 19234194

Title: Human SCAMP5, a novel secretory carrier membrane protein, facilitates calcium-triggered cytokine secretion by interaction with SNARE machinery.

PubMed ID: 19234194

DOI: 10.4049/jimmunol.0802002

PubMed ID: 23999003

Title: SYT14L, especially its C2 domain, is involved in regulating melanocyte differentiation.

PubMed ID: 23999003

DOI: 10.1016/j.jdermsci.2013.07.010

PubMed ID: 25192047

Title: Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy.

PubMed ID: 25192047

DOI: 10.1016/j.ajhg.2014.08.007

PubMed ID: 32250532

Title: Recessive congenital myasthenic syndrome caused by a homozygous mutation in SYT2 altering a highly conserved C-terminal amino acid sequence.

PubMed ID: 32250532

DOI: 10.1002/ajmg.a.61579

PubMed ID: 32776697

Title: Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome.

PubMed ID: 32776697

DOI: 10.1002/ajmg.a.61765

PubMed ID: 33659639

Title: New recessive mutations in SYT2 causing severe presynaptic congenital myasthenic syndromes.

PubMed ID: 33659639

DOI: 10.1212/nxg.0000000000000534

PubMed ID: 33320396

Title: A new de novo SYT2 mutation presenting as distal weakness. Neuropathy or neuromuscular junction dysfunction?

PubMed ID: 33320396

DOI: 10.1111/jns.12425

PubMed ID: 34151484

Title:

PubMed ID: 34151484

DOI: 10.1111/jns.12441

PubMed ID: 34037996

Title: Dominant and recessive congenital myasthenic syndromes caused by SYT2 mutations.

PubMed ID: 34037996

DOI: 10.1002/mus.27332

Sequence Information:

  • Length: 419
  • Mass: 46872
  • Checksum: BE3855E9CDE2D76E
  • Sequence:
    • MRNIFKRNQE PIVAPATTTA TMPIGPVDNS TESGGAGESQ EDMFAKLKEK LFNEINKIPL 
PPWALIAIAV VAGLLLLTCC FCICKKCCCK KKKNKKEKGK GMKNAMNMKD MKGGQDDDDA 
ETGLTEGEGE GEEEKEPENL GKLQFSLDYD FQANQLTVGV LQAAELPALD MGGTSDPYVK 
VFLLPDKKKK YETKVHRKTL NPAFNETFTF KVPYQELGGK TLVMAIYDFD RFSKHDIIGE 
VKVPMNTVDL GQPIEEWRDL QGGEKEEPEK LGDICTSLRY VPTAGKLTVC ILEAKNLKKM 
DVGGLSDPYV KIHLMQNGKR LKKKKTTVKK KTLNPYFNES FSFEIPFEQI QKVQVVVTVL 
DYDKLGKNEA IGKIFVGSNA TGTELRHWSD MLANPRRPIA QWHSLKPEEE VDALLGKNK