VAMP2
protein-codingvesicle associated membrane protein 2, the group of Vesicle associated membrane proteins
Gene summary
The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. This gene is thought to participate in neurotransmitter release at a step between docking and fusion. The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and synaptotagmin. It also forms a distinct complex with synaptophysin. It is a likely candidate gene for familial infantile myasthenia (FIMG) because of its map location and because it encodes a synaptic vesicle protein of the type that has been implicated in the pathogenesis of FIMG. [provided by RefSeq, Jul 2008]
- SYB2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0032900
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0032900
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0032900
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0032900
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VAMP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014232.3. 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 | 7 | 7 | ||||
| missense | 4 | 3 | 23 | 2 | 32 | |
| nonsense | 1 | 1 | 1 | 3 | ||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 6 | 6 | 27 | 9 | 0 | 48 |
Highest pathogenic variant AF is 0.0000031130264
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055047.2 | 5 | MANE Select | |
| Ensembl | ENSP00000314214.6 | 5 | MANE Select | |
| RefSeq | NP_001317054.1 | 5 | Standard | |
| Ensembl | ENSP00000466995.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Synaptic vesicle cycle - Homo sapiens (human)
- Vasopressin-regulated water reabsorption - Homo sapiens (human)
- SNARE interactions in vesicular transport - Homo sapiens (human)
- Salivary secretion - Homo sapiens (human)
- Insulin secretion - Homo sapiens (human)
Biological Process
- exocytosis
- response to glucose
- glutamate secretion
- protein transport
- synaptic vesicle exocytosis
Molecular Function
- SNARE binding
- protein binding
- calmodulin binding
- phospholipid binding
- syntaxin-1 binding
Cellular Component
- trans-Golgi network
- cytosol
- plasma membrane
- integral component of plasma membrane
- synaptic vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316509
- Coding exons
- 5
- Length
- 4398
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.41 | 36 | 69.0 | 0.521 | 0.00000377 | 752 |
| Missense (PolyPhen) | 1 | 16.956 | 0.058976 | 209 | ||
| Synonymous | -1.26 | 36 | 27.6 | 1.30 | 0.00000169 | 232 |
| Loss of Function | 2.47 | 0 | 7.10 | 0.00 | 3.87e-7 | 78 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the targeting and/or fusion of transport vesicles to their target membrane. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. {ECO:0000250|UniProtKB:P63045}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.988