SYT5
protein-codingsynaptotagmin 5, the group of Synaptotagmins
Gene summary
Synaptotagmins, such as SYT5, are a family of type III membrane proteins characterized by cytoplasmic repeats related to protein kinase C (see MIM 176960) regulatory (C2) domains, which are thought to bind calcium. Synaptotagmins may act both as negative regulators of vesicle fusion, allowing fusion in the presence of calcium, and as calcium receptors or sensor molecules (summary by Hudson and Birnbaum, 1995 [PubMed 7597049]).[supplied by OMIM, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.1 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 SYT5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003180.3. 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 | 59 | 1 | 60 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 60 | 2 | 0 | 62 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003171.2 | 8 | MANE Select | |
| Ensembl | ENSP00000346265.2 | 8 | MANE Select | |
| RefSeq | NP_001284703.1 | 7 | Standard | |
| Ensembl | ENSP00000442896.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- chemical synaptic transmission
- regulation of dopamine secretion
- synaptic vesicle exocytosis
- vesicle-mediated transport
- calcium ion regulated exocytosis
Molecular Function
- SNARE binding
- phosphatidylserine binding
- calcium ion binding
- calcium-dependent phospholipid binding
- phosphatidylinositol-4,5-bisphosphate binding
Cellular Component
- plasma membrane
- cell junction
- axon
- synaptic vesicle membrane
- dense core granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354308
- Coding exons
- 8
- Length
- 9243
- Individuals with no LoFs
- 125712
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 36
- Defined
- 125748
- p
- 0.000143
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.19 | 168 | 218 | 0.772 | 0.0000134 | 2431 |
| Missense (PolyPhen) | 52 | 79.666 | 0.65273 | 905 | ||
| Synonymous | 0.731 | 87 | 96.1 | 0.905 | 0.00000604 | 813 |
| Loss of Function | 2.04 | 7 | 15.7 | 0.445 | 7.40e-7 | 192 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000092 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.000048 | 0.000033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. Regulates the Ca(2+)- dependent secretion of norepinephrine in PC12 cells. Required for export from the endocytic recycling compartment to the cell surface (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.175
Intolerance Scores
- LoFtool
- 0.790
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.45
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.325
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |