SYTL4
protein-codingsynaptotagmin like 4, the group of Synaptotagmin like tandem C2 proteins
Gene summary
This gene encodes a member of the synaptotagmin like protein family. Members of this family are characterized by an N-terminal Rab27 binding domain and C-terminal tandem C2 domains. The encoded protein binds specific small Rab GTPases and is involved in intracellular membrane trafficking. This protein binds Rab27 and may be involved in inhibiting dense core vesicle exocytosis. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0005283
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SYTL4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001370165.1. 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 | 14 | 1 | 15 | |||
| missense | 105 | 3 | 108 | |||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 17 | 17 | ||||
| Total | 0 | 0 | 140 | 4 | 0 | 144 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001357094.1 | 16 | MANE Select | |
| Ensembl | ENSP00000362080.1 | 16 | MANE Select | |
| RefSeq | NP_001123368.1 | 16 | Standard | |
| RefSeq | NP_001167539.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Deregulation of Rab and Rab Effector Genes in Bladder Cancer
- Platelet degranulation
- Response to elevated platelet cytosolic Ca2+
- Platelet activation, signaling and aggregation
- Hemostasis
Biological Process
- platelet degranulation
- intracellular protein transport
- positive regulation of exocytosis
- negative regulation of insulin secretion
- positive regulation of protein secretion
Molecular Function
- protein binding
- phospholipid binding
- Rab GTPase binding
- neurexin family protein binding
- metal ion binding
Cellular Component
- nucleoplasm
- endosome
- microtubule organizing center
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000455616
- Coding exons
- 16
- Length
- 57623
- Individuals with no LoFs
- 125701
- Homozygous LoFs
- 10
- Heterozygous LoFs
- 26
- Defined
- 125737
- p
- 0.000143
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.812 | 222 | 259 | 0.858 | 0.0000204 | 4430 |
| Missense (PolyPhen) | 70 | 94.865 | 0.73789 | 1587 | ||
| Synonymous | 2.15 | 65 | 91.1 | 0.713 | 0.00000661 | 1255 |
| Loss of Function | 3.21 | 8 | 25.5 | 0.314 | 0.00000191 | 444 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00053 | 0.00040 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00022 | 0.00015 | rare |
| South Asian | 0.000060 | 0.000033 | rare |
| Other | 0.00095 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary. Interacts with vesicles containing negatively charged phospholipids in a Ca(2+)-independent manner (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.129
Intolerance Scores
- LoFtool
- 0.729
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.44
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.524
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |