SYT8
protein-codingsynaptotagmin 8, the group of Synaptotagmins
Gene summary
This gene encodes a member of the synaptotagmin protein family. Synaptotagmins are membrane proteins that are important in neurotransmission and hormone secretion, both of which involve regulated exocytosis. Expression of the encoded protein in human pancreatic islets has been connected to activity of the promoter for the insulin gene, on the same chromosome several hundred kilobases away (PMID: 21336277 and 22928559). This association would link response to gluclose to insulin secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.2 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 SYT8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001394072.1. 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 | ||||
| missense | 85 | 3 | 2 | 90 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 88 | 4 | 2 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001381001.1 | 8 | MANE Select | |
| Ensembl | ENSP00000343691.3 | 8 | MANE Select | |
| RefSeq | NP_001277261.2 | 9 | Standard | |
| RefSeq | NP_001277262.2 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Clathrin-mediated endocytosis
- Cargo recognition for clathrin-mediated endocytosis
Biological Process
- acrosome reaction
- 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
- syntaxin binding
Cellular Component
- acrosomal vesicle
- plasma membrane
- integral component of membrane
- axon
- synaptic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381968
- Coding exons
- 9
- Length
- 10043
- Individuals with no LoFs
- 125435
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 250
- Defined
- 125686
- p
- 0.000999
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.237 | 261 | 250 | 1.04 | 0.0000166 | 2504 |
| Missense (PolyPhen) | 54 | 53.012 | 1.0186 | 711 | ||
| Synonymous | -1.68 | 135 | 112 | 1.20 | 0.00000760 | 884 |
| Loss of Function | -2.41 | 30 | 18.7 | 1.60 | 0.00000102 | 183 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00076 | 0.00074 | rare |
| Latino/Admixed American | 0.0033 | 0.0031 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0.00015 | 0.00014 | rare |
| European (Non-Finnish) | 0.00094 | 0.00090 | rare |
| South Asian | 0.00054 | 0.00052 | rare |
| Other | 0.0012 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Isoform 4 may play a role in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Mediates Ca(2+)-regulation of exocytosis acrosomal reaction in sperm. May mediate Ca(2+)-regulation of exocytosis in insulin secreted cells (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.820
- RVIS EVS
- 1.16
- RVIS percentile EVS
- 92.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.464
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |