SYT1
synaptotagmin 1, the group of Synaptotagmins|MicroRNA protein coding host genes
Basic information
Region (hg38): 12:78863993-79452008
Previous symbols: [ "SYT", "SVP65" ]
Links
Phenotypes
GenCC
Source:
- infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome (Moderate), mode of inheritance: AD
- infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome (Moderate), mode of inheritance: AD
- infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome (Strong), mode of inheritance: AD
- infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Baker-Gordon syndrome | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic | 25705886; 30107533 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (40 variants)
- Infantile_hypotonia-oculomotor_anomalies-hyperkinetic_movements-developmental_delay_syndrome (25 variants)
- Inborn_genetic_diseases (25 variants)
- SYT1-related_disorder (7 variants)
- SYT1-associated_neurodevelopmental_disorder (6 variants)
- not_specified (2 variants)
- Neurodevelopmental_disorder (1 variants)
- Syndromic_intellectual_disability (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005639.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | 12 | ||||
| missense | 16 | 52 | 71 | |||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 2 | 16 | 57 | 13 | 1 |
Highest pathogenic variant AF is 0.00000136816
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SYT1 | protein_coding | protein_coding | ENST00000261205 | 8 | 588016 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.600 | 0.400 | 125741 | 0 | 6 | 125747 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.84 | 109 | 230 | 0.474 | 0.0000118 | 2791 |
| Missense in Polyphen | 11 | 73.827 | 0.149 | 918 | ||
| Synonymous | 0.229 | 89 | 91.8 | 0.970 | 0.00000536 | 780 |
| Loss of Function | 3.35 | 4 | 20.3 | 0.197 | 0.00000111 | 253 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.000102 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.0000268 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003}.;
- Disease
- DISEASE: Note=A SYT1 rare mutation has been found in a child with a severe neuro-developmental disorder. The individual harboring this variant shows early onset dyskinetic movement disorder, severe motor delay and profound cognitive impairment, suggesting that SYT1 may play a role in the pathogenesis of this neuro- developmental disorder. {ECO:0000269|PubMed:25705886}.;
- Pathway
- Synaptic vesicle cycle - Homo sapiens (human);Synaptic Vesicle Pathway;Disease;Vesicle-mediated transport;Membrane Trafficking;Effects of Botulinum toxin;Uptake and actions of bacterial toxins;Toxicity of botulinum toxin type G (BoNT/G);Neurotoxicity of clostridium toxins;Infectious disease;Neuronal System;Clathrin-mediated endocytosis;Glutamate Neurotransmitter Release Cycle;Dopamine Neurotransmitter Release Cycle;Acetylcholine Neurotransmitter Release Cycle;Toxicity of botulinum toxin type B (BoNT/B);GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Neurexins and neuroligins;Cargo recognition for clathrin-mediated endocytosis;Transmission across Chemical Synapses;Protein-protein interactions at synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle
(Consensus)
Recessive Scores
- pRec
- 0.466
Intolerance Scores
- loftool
- 0.484
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 43.29
Haploinsufficiency Scores
- pHI
- 0.408
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.580
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.786
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Syt1
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype;
Gene ontology
- Biological process
- detection of calcium ion;chemical synaptic transmission;neurotransmitter secretion;brain development;glutamate secretion;regulation of dopamine secretion;synaptic vesicle exocytosis;vesicle-mediated transport;calcium ion regulated exocytosis;regulation of exocytosis;regulation of calcium ion-dependent exocytosis;vesicle docking;synaptic vesicle endocytosis;calcium ion-regulated exocytosis of neurotransmitter;positive regulation of synaptic transmission;protein homooligomerization;protein heterooligomerization;regulation of synaptic transmission, glutamatergic;membrane organization;cellular response to calcium ion;fast, calcium ion-dependent exocytosis of neurotransmitter;calcium-dependent activation of synaptic vesicle fusion;regulation of regulated secretory pathway;positive regulation of dendrite extension
- Cellular component
- cytoplasm;Golgi apparatus;plasma membrane;synaptic vesicle;cell junction;integral component of synaptic vesicle membrane;axon;clathrin-coated vesicle membrane;synaptic vesicle membrane;dense core granule;SNARE complex;chromaffin granule membrane;presynaptic membrane;neuron projection;neuron projection terminus;excitatory synapse;clathrin-sculpted acetylcholine transport vesicle membrane;clathrin-sculpted glutamate transport vesicle membrane;clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane;clathrin-sculpted monoamine transport vesicle membrane;exocytic vesicle;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse
- Molecular function
- SNARE binding;phosphatidylserine binding;calcium ion binding;protein binding;calmodulin binding;calcium-dependent phospholipid binding;1-phosphatidylinositol binding;phosphatidylinositol-4,5-bisphosphate binding;protein C-terminus binding;syntaxin-1 binding;syntaxin binding;clathrin binding;syntaxin-3 binding;identical protein binding;protein heterodimerization activity;calcium-dependent protein binding;low-density lipoprotein particle receptor binding