VAMP2

vesicle associated membrane protein 2, the group of Vesicle associated membrane proteins

Basic information

Region (hg38): 17:8159149-8163546

Previous symbols: [ "SYB2" ]

Links

ENSG00000220205 ∙ NCBI:6844 ∙ OMIM:185881 ∙ HGNC:12643 ∙ Uniprot:P63027 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements	AD	General	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	Neurologic	30929742

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VAMP2 gene.

• not provided (2 variants)
• Severe neurodevelopmental delay (1 variants)
• Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VAMP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4		4
missense		2	10			12
nonsense	1	1				2
start loss	1					1
frameshift		1	1			2
inframe indel	1					1
splice donor/acceptor (+/-2bp)			1			1
splice region				1		1
non coding					1	1
Total	3	4	12	4	1

Variants in VAMP2

This is a list of pathogenic ClinVar variants found in the VAMP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-8160864-GAAGTA-G			Likely pathogenic (Jun 18, 2020)
17-8161461-C-G		Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements	Benign (Dec 05, 2021)
17-8161479-T-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 03, 2023)
17-8161491-T-G		Inborn genetic diseases	Uncertain significance (Oct 08, 2024)
17-8161498-G-A			Likely benign (Dec 01, 2023)
17-8161513-G-A			Likely benign (Oct 01, 2023)
17-8161634-G-A			Uncertain significance (Mar 26, 2023)
17-8161657-T-G		Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements	Pathogenic (Jan 31, 2020)
17-8161660-A-G		Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements	Pathogenic (Jan 31, 2020)
17-8161664-G-A		Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements	Likely pathogenic (Mar 01, 2024)
17-8161667-A-G		Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements	Pathogenic (Jan 31, 2020)
17-8161669-G-A		Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements • Inborn genetic diseases	Uncertain significance (Apr 09, 2020)
17-8161673-C-A			Likely pathogenic (Jun 18, 2020)
17-8161690-G-A			Uncertain significance (Sep 01, 2022)
17-8161693-C-T			Uncertain significance (Oct 14, 2022)
17-8161707-C-T		VAMP2-related disorder	Likely benign (Sep 17, 2019)
17-8161723-C-A			Likely pathogenic (Jun 18, 2020)
17-8161724-G-A			Pathogenic (Jun 18, 2020)
17-8161743-G-A		VAMP2-related disorder	Likely benign (Jul 20, 2022)
17-8161752-CATG-C		Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements	Pathogenic (Feb 01, 2020)
17-8161759-TCCA-T		Severe neurodevelopmental delay • Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements	Pathogenic (Jul 10, 2019)
17-8161767-C-G			Uncertain significance (Jul 28, 2022)
17-8161769-G-A		Inborn genetic diseases • VAMP2-related disorder	Likely benign (Aug 09, 2021)
17-8162290-T-C			Likely benign (Jul 01, 2024)
17-8162296-G-C		VAMP2-related disorder	Uncertain significance (Jun 14, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VAMP2	protein_coding	protein_coding	ENST00000316509	5	4398

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.887	0.112	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	36	69.0	0.521	0.00000377	752
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Synaptic Vesicle Pathway;Insulin Signaling;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Golgi Associated Vesicle Biogenesis;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Disease;trans-Golgi Network Vesicle Budding;Other interleukin signaling;Signaling by Interleukins;Vesicle-mediated transport;Membrane Trafficking;Cytokine Signaling in Immune system;Toxicity of tetanus toxin (TeNT);Effects of Botulinum toxin;Toxicity of botulinum toxin type D (BoNT/D);Toxicity of botulinum toxin type F (BoNT/F);Uptake and actions of bacterial toxins;Toxicity of botulinum toxin type G (BoNT/G);Neurotoxicity of clostridium toxins;Infectious disease;Immune System;Neuronal System;Clathrin-mediated endocytosis;Glutamate Neurotransmitter Release Cycle;Dopamine Neurotransmitter Release Cycle;Acetylcholine Neurotransmitter Release Cycle;Toxicity of botulinum toxin type B (BoNT/B);GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Cargo recognition for clathrin-mediated endocytosis;Transmission across Chemical Synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle;Insulin-mediated glucose transport (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.39

Haploinsufficiency Scores

• pHI: 0.425
• hipred: Y
• hipred_score: 0.598
• ghis: 0.648

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Mouse Genome Informatics

• Gene name: Vamp2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: exocytosis;response to glucose;glutamate secretion;protein transport;synaptic vesicle exocytosis;vesicle-mediated transport;calcium ion regulated exocytosis;regulation of exocytosis;cellular response to insulin stimulus;Golgi to plasma membrane protein transport;eosinophil degranulation;neutrophil degranulation;natural killer cell degranulation;long-term synaptic potentiation;regulation of vesicle-mediated transport;membrane organization;membrane fusion;protein-containing complex assembly;mucus secretion;positive regulation of intracellular protein transport;regulation of delayed rectifier potassium channel activity;regulation of histamine secretion by mast cell
• Cellular component: trans-Golgi network;cytosol;plasma membrane;integral component of plasma membrane;synaptic vesicle;voltage-gated potassium channel complex;membrane;cell junction;clathrin-coated vesicle;secretory granule;clathrin-coated vesicle membrane;secretory granule membrane;synaptic vesicle membrane;SNARE complex;cytoplasmic vesicle;vesicle;zymogen granule membrane;neuron projection;intracellular membrane-bounded organelle;neuron projection terminus;synapse;perinuclear region of cytoplasm;clathrin-sculpted glutamate transport vesicle membrane;clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane;synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex;synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex;synaptobrevin 2-SNAP-25-syntaxin-1a complex;clathrin-sculpted monoamine transport vesicle membrane
• Molecular function: SNARE binding;protein binding;calmodulin binding;phospholipid binding;syntaxin-1 binding;syntaxin binding;protein self-association;calcium-dependent protein binding