VAMP1

vesicle associated membrane protein 1, the group of Vesicle associated membrane proteins

Basic information

Region (hg38): 12:6462237-6470677

Previous symbols: [ "SYB1" ]

Links

ENSG00000139190 ∙ NCBI:6843 ∙ OMIM:185880 ∙ HGNC:12642 ∙ Uniprot:P23763 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myasthenic syndrome, congenital, 25, presynaptic (Strong), mode of inheritance: AR
• myasthenic syndrome, congenital, 25, presynaptic (Strong), mode of inheritance: AR
• presynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AD
• spastic ataxia 1 (Supportive), mode of inheritance: AD
• myasthenic syndrome, congenital, 25, presynaptic (Strong), mode of inheritance: AR
• spastic ataxia 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 25, presynaptic	AR	Musculoskeletal; Neurologic	The condition can involve neonatal hypotonia and generalized muscle weakness, and medicial management (with pyridostigmine) has been described as beneficial	Musculoskeletal; Neurologic	11774073; 22958904; 28168212; 28253535; 28600779

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VAMP1 gene.

• Spastic paraplegia (5 variants)
• not provided (3 variants)
• Spastic ataxia 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VAMP1 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			1	10	1	12
missense	2		29	3		34
nonsense	1	1				2
start loss						0
frameshift	2	2	2			6
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	2		4
non coding			3	20	14	37
Total	5	3	35	33	15

Variants in VAMP1

This is a list of pathogenic ClinVar variants found in the VAMP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-6462840-G-A			Benign/Likely benign (Jan 01, 2024)
12-6462882-A-G		Myasthenic syndrome, congenital, 25, presynaptic • Spastic ataxia 1	Benign (Dec 05, 2021)
12-6463025-T-C			Benign (May 15, 2021)
12-6464474-G-A		Spastic paraplegia	Uncertain significance (Aug 22, 2022)
12-6464476-A-G		Spastic paraplegia	Likely benign (Aug 16, 2022)
12-6464481-A-G		Spastic paraplegia	Uncertain significance (Dec 09, 2022)
12-6464486-A-G		Spastic paraplegia	Uncertain significance (Nov 06, 2021)
12-6464488-T-C		Myasthenic syndrome, congenital, 25, presynaptic • Spastic paraplegia	Uncertain significance (Sep 08, 2023)
12-6464496-G-A		Spastic paraplegia	Likely benign (Oct 05, 2023)
12-6464501-CAGG-C		Spastic paraplegia	Likely benign (Jan 03, 2023)
12-6464504-G-T		Spastic paraplegia	Uncertain significance (Sep 19, 2023)
12-6464505-A-C		Spastic paraplegia	Likely benign (Nov 28, 2023)
12-6464505-AAG-TTT		Spastic paraplegia	Likely benign (Jan 03, 2023)
12-6464510-C-T		Myasthenic syndrome, congenital, 25, presynaptic	Likely pathogenic (Jun 01, 2022)
12-6464550-T-C			Benign (May 15, 2021)
12-6464551-G-A			Benign (May 25, 2021)
12-6464583-C-T			Benign (May 15, 2021)
12-6464690-G-T			Benign (May 15, 2021)
12-6464744-C-T			Benign (May 25, 2021)
12-6464870-G-A		Spastic paraplegia	Likely benign (Nov 27, 2023)
12-6464874-C-T		Spastic paraplegia	Likely benign (Nov 01, 2022)
12-6464878-A-C		Spastic paraplegia	Likely benign (Mar 28, 2022)
12-6464880-C-T		Spastic paraplegia	Likely benign (Jun 20, 2022)
12-6464881-G-A		Spastic paraplegia	Likely benign (May 13, 2023)
12-6464888-A-C		Spastic ataxia 1 • Spastic paraplegia	Pathogenic (Jun 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VAMP1	protein_coding	protein_coding	ENST00000396308	5	8751

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00394	0.867	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.23	38	66.3	0.573	0.00000332	764
Missense in Polyphen		10	16.869	0.5928		222
Synonymous	0.471	20	22.9	0.875	0.00000112	233
Loss of Function	1.28	5	9.18	0.545	5.76e-7	87

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the targeting and/or fusion of transport vesicles to their target membrane.
• Disease: DISEASE: Spastic ataxia 1, autosomal dominant (SPAX1) [MIM:108600]: An autosomal dominant form of spastic ataxia, a progressive neurodegenerative disorder characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance. {ECO:0000269|PubMed:22958904}. Note=The disease is caused by mutations affecting the gene represented in this entry. A mutation affecting a critical donor site for the splicing of VAMP1 isoforms leads to the loss of neuron-specific isoform 1 and subsequently results in haploinsufficiency (PubMed:22958904). Therefore, there would be less neurotransmitter exocytosis in specific regions of the brain, causing the symptoms of SPAX1. {ECO:0000303|PubMed:22958904}.
• Pathway: SNARE interactions in vesicular transport - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Disease;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 (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• rvis_EVS: 0.24
• rvis_percentile_EVS: 68.72

Haploinsufficiency Scores

• pHI: 0.174
• hipred: Y
• hipred_score: 0.514
• ghis: 0.552

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.815

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Vamp1
• Phenotype: growth/size/body region phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: synaptic vesicle priming;regulation of synaptic vesicle fusion to presynaptic active zone membrane;SNARE complex assembly
• Cellular component: mitochondrial outer membrane;cytosol;integral component of plasma membrane;cell surface;cell junction;integral component of synaptic vesicle membrane;synaptic vesicle membrane;neuromuscular junction;azurophil granule membrane;specific granule membrane;neuron projection;tertiary granule membrane;glutamatergic synapse
• Molecular function: protein binding