SYT12
protein-codingsynaptotagmin 12, the group of MicroRNA protein coding host genes|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. Studies of the orthologous gene in rat have shown that the encoded protein selectively modulates spontaneous synaptic-vesicle exocytosis and may also be involved in regulating calcium independent secretion in nonneuronal cells. Alternative splicing results in multiple transcript variants. The gene has previously been referred to as synaptotagmin XI but has been renamed synaptotagmin XII to be standard with mouse and rat official nomenclature.[provided by RefSeq, Apr 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.1 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 SYT12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_177963.4. 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 | 2 | 2 | ||||
| missense | 86 | 2 | 88 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 89 | 2 | 0 | 91 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_808878.1 | 7 | MANE Select | |
| Ensembl | ENSP00000435316.1 | 7 | MANE Select | |
| RefSeq | NP_001171351.1 | 7 | Standard | |
| RefSeq | NP_001305702.1 | 5 | Standard |
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
- regulation of dopamine secretion
- vesicle-mediated transport
- calcium ion regulated exocytosis
- regulation of calcium ion-dependent exocytosis
- regulation of neurotransmitter secretion
Molecular Function
- SNARE binding
- phosphatidylserine binding
- calcium ion binding
- calcium-dependent phospholipid binding
- clathrin binding
Cellular Component
- plasma membrane
- integral component of membrane
- cell junction
- synaptic vesicle membrane
- exocytic vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393946
- Coding exons
- 7
- Length
- 44086
- 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 | 0.307 | 264 | 278 | 0.948 | 0.0000184 | 2753 |
| Missense (PolyPhen) | 73 | 75.38 | 0.96842 | 731 | ||
| Synonymous | 0.318 | 119 | 124 | 0.964 | 0.00000896 | 860 |
| Loss of Function | 1.51 | 10 | 16.7 | 0.600 | 7.14e-7 | 187 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000090 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00020 | 0.00019 | rare |
| South Asian | 0.00027 | 0.00026 | rare |
| Other | 0 | 0.0 | absent |
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. {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.816
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 32.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.394
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |