SYT7
protein-codingsynaptotagmin 7, the group of Synaptotagmins
Gene summary
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. A similar protein in rodents mediates hormone secretion and lysosome exocytosis. In humans, expression of this gene has been associated with prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]
- PCANAP7
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~67.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SYT7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001365809.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 40 | 1 | 1 | 42 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 44 | 2 | 1 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001352738.1 | 13 | MANE Select | |
| Ensembl | ENSP00000439694.1 | 13 | MANE Select | |
| RefSeq | NP_001238994.1 | 10 | Standard | |
| RefSeq | NP_001287702.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| syt7b | Danio rerio | Structure: motor neuron Quality: physical object quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuronal System
- Neurexins and neuroligins
- Protein-protein interactions at synapses
Biological Process
- plasma membrane repair
- phagocytosis
- regulation of dopamine secretion
- vesicle-mediated transport
- calcium ion regulated exocytosis
Molecular Function
- SNARE binding
- phosphatidylserine binding
- calcium ion binding
- protein binding
- calmodulin binding
Cellular Component
- lysosome
- lysosomal membrane
- peroxisome
- peroxisomal membrane
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000540677
- Coding exons
- 10
- Length
- 65836
- Individuals with no LoFs
- 125090
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125092
- p
- 0.00000799
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.21 | 189 | 296 | 0.638 | 0.0000203 | 3094 |
| Missense (PolyPhen) | 28 | 76.981 | 0.36373 | 827 | ||
| Synonymous | 0.174 | 130 | 133 | 0.981 | 0.0000103 | 955 |
| Loss of Function | 3.63 | 2 | 19.1 | 0.105 | 9.86e-7 | 245 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain (By similarity). Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis (By similarity). SYT7 binds Ca(2+) with high affinity and slow kinetics compared to other synaptotagmins (By similarity). Involved in Ca(2+)-triggered lysosomal exocytosis, a major component of the plasma membrane repair (PubMed:11342594). Ca(2+)- regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (By similarity). Ca(2+)-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (By similarity). In case of infection, involved in participates cell invasion by Trypanosoma cruzi via Ca(2+)-triggered lysosomal exocytosis (PubMed:11342594, PubMed:15811535). Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5-bisphosphate on peroxisomal membranes (By similarity). Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca(2+) into the axon terminal after spike generation, increasing the release probability of neurotransmitters (By similarity). Probably mediates synaptic facilitation by directly increasing the probability of release (By similarity). May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca(2+) and by forming a complex with calmodulin (By similarity). Also acts as a regulator of Ca(2+)-dependent insulin and glucagon secretion in beta-cells (By similarity). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (By similarity). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity). {ECO:0000250|UniProtKB:Q62747, ECO:0000250|UniProtKB:Q9R0N7, ECO:0000269|PubMed:11342594, ECO:0000269|PubMed:15811535}.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- LoFtool
- 0.139
- RVIS EVS
- -0.67
- RVIS percentile EVS
- 15.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.757
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |