VAMP1

Summary

VAMP1 (vesicle associated membrane protein 1, HGNC:12642) is a protein-coding gene on chromosome 12p13.31, encoding Vesicle-associated membrane protein 1 (P23763). Involved in the targeting and/or fusion of transport vesicles to their target membrane.

Synapotobrevins, syntaxins, and the 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. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Mutations in this gene are associated with autosomal dominant spastic ataxia 1. Multiple alternative splice variants have been described, but the full-length nature of some variants has not been defined.

Source: NCBI Gene 6843 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myasthenic syndrome, congenital, 25, presynaptic (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 11 total — 1 likely-pathogenic
• Phenotypes (HPO): 108
• MANE Select transcript: NM_014231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12642
Approved symbol	VAMP1
Name	vesicle associated membrane protein 1
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	VAMP-1
Ensembl gene	ENSG00000139190
Ensembl biotype	protein_coding
OMIM	185880
Entrez	6843

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000361716, ENST00000396308, ENST00000400911, ENST00000535180, ENST00000535927, ENST00000538970, ENST00000539047, ENST00000544432

RefSeq mRNA: 4 — MANE Select: NM_014231 NM_001297438, NM_014231, NM_016830, NM_199245

CCDS: CCDS31731, CCDS41740, CCDS44809, CCDS73422

Canonical transcript exons

ENST00000396308 — 5 exons

Exon	Start	End
ENSE00001631548	6462237	6464486
ENSE00003514778	6464890	6464941
ENSE00003532754	6465842	6466000
ENSE00003605934	6466225	6466351
ENSE00003682594	6470530	6470677

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7633 / max 508.2049, expressed in 1658 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129100	11.9991	1641
129099	0.3796	156
129098	0.1514	56
129101	0.1349	66
129102	0.0983	27

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.53	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.43	gold quality
primary visual cortex	UBERON:0002436	99.05	gold quality
superior vestibular nucleus	UBERON:0007227	98.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.66	gold quality
dorsal root ganglion	UBERON:0000044	98.60	gold quality
endothelial cell	CL:0000115	98.46	gold quality
middle temporal gyrus	UBERON:0002771	98.43	gold quality
medulla oblongata	UBERON:0001896	98.34	gold quality
occipital lobe	UBERON:0002021	98.17	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.80	gold quality
inferior olivary complex	UBERON:0002127	97.75	gold quality
ventral tegmental area	UBERON:0002691	97.72	gold quality
postcentral gyrus	UBERON:0002581	97.68	gold quality
parietal lobe	UBERON:0001872	97.66	gold quality
spinal cord	UBERON:0002240	96.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.54	gold quality
trigeminal ganglion	UBERON:0001675	96.26	gold quality
superior frontal gyrus	UBERON:0002661	96.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.14	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.13	gold quality
inferior vagus X ganglion	UBERON:0005363	96.09	gold quality
midbrain	UBERON:0001891	96.07	gold quality
substantia nigra	UBERON:0002038	95.85	gold quality
substantia nigra pars compacta	UBERON:0001965	95.77	gold quality
lateral globus pallidus	UBERON:0002476	95.74	gold quality
hypothalamus	UBERON:0001898	95.22	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.15	gold quality
right frontal lobe	UBERON:0002810	95.11	gold quality
prefrontal cortex	UBERON:0000451	95.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting VAMP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1284	99.67	73.56	1353

Literature-anchored findings (GeneRIF, showing 10)

• locus for autosomal dominant hereditary spastic ataxia, SAX1, maps to chromosome 12p (PMID:11774073)
• The expression of the SNARE protein SNAP-25 and its cellular homologue SNAP-23, as well as syntaxin1 and VAMP (vesicle-associated membrane protein) in samples of normal parathyroid tissue, chief cell adenoma, and parathyroid carcinoma, was examined. (PMID:18457912)
• multiple domains outside the R-SNARE of tomosyn are critical to the efficacy of inhibition by tomosyn on exocytotic secretion (PMID:21330375)
• This report identifies vesicle-associated membrane protein 1 (VAMP1), which encodes a critical protein for synaptic exocytosis, as the responsible gene fora dominantly inherited spastic ataxia (PMID:22958904)
• residue 48 of VAMP1 varies frequently between M and I across seventeen closely related primate species, suggesting a potential selective pressure from members of BoNTs for resistance in vertebrates. (PMID:25010769)
• Genetically regulated VAMP1 expression in the brain may modify both Alzheimer’s disease risk and may contribute to Alzheimer’s pathophysiology (PMID:25881291)
• VAMP1 homozygous mutations causes of presynaptic congenital myasthenic syndrome. (PMID:28253535)
• Recessive VAMP1 mutations associated with severe congenital myasthenic syndromes - A recognizable clinical phenotype. (PMID:33631708)
• Prefrontal cortex VAMP1 gene network moderates the effect of the early environment on cognitive flexibility in children. (PMID:34454100)
• Expanding the genetic and phenotypic spectrum of congenital myasthenic syndrome: new homozygous VAMP1 splicing variants in 2 novel individuals. (PMID:38355957)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vamp1	ENSMUSG00000030337
rattus_norvegicus	Vamp1	ENSRNOG00000019219
drosophila_melanogaster	Syb	FBGN0003660
caenorhabditis_elegans		WBGENE00004898
caenorhabditis_elegans		WBGENE00004899
caenorhabditis_elegans		WBGENE00014084
caenorhabditis_elegans		WBGENE00044062

Paralogs (10): VAMP3 (ENSG00000049245), SEC22C (ENSG00000093183), YKT6 (ENSG00000106636), VAMP4 (ENSG00000117533), VAMP8 (ENSG00000118640), SEC22A (ENSG00000121542), VAMP7 (ENSG00000124333), VAMP5 (ENSG00000168899), VAMP2 (ENSG00000220205), SEC22B (ENSG00000265808)

Protein

Protein identifiers

Vesicle-associated membrane protein 1 — P23763 (reviewed: P23763)

Alternative names: Synaptobrevin-1

All UniProt accessions (2): P23763, F5GZV7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the targeting and/or fusion of transport vesicles to their target membrane.

Subunit / interactions. Interacts with VAPA and VAPB.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Synapse. Synaptosome Cytoplasmic vesicle membrane. Synaptosome Mitochondrion outer membrane.

Tissue specificity. Nervous system, skeletal muscle and adipose tissue.

Post-translational modifications. (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type B (BoNT/B, botB) which probably hydrolyzes the 78-Gln-|-Phe-79 bond and inhibits neurotransmitter release. (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type D (BoNT/D, botD) which probably hydrolyzes the 61-Arg-|-Leu-62 bond and inhibits neurotransmitter release. BoNT/D has low catalytic activity on this protein due to its sequence. Note that humans are not known to be infected by C.botulinum type D. (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type F (BoNT/F, botF) which probably hydrolyzes the 60-Gln-|-Lys-61 bond and inhibits neurotransmitter release. (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type X (BoNT/X) which probably hydrolyzes the 68-Arg-|-Ala-69 bond and inhibits neurotransmitter release. It remains unknown whether BoNT/X is ever produced, or what organisms it targets.

Disease relevance. 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. The disease is caused by variants 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. Therefore, there would be less neurotransmitter exocytosis in specific regions of the brain, causing the symptoms of SPAX1. Myasthenic syndrome, congenital, 25, presynaptic (CMS25) [MIM:618323] A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS25 is an autosomal recessive form characterized by hypotonia and generalized muscle weakness apparent from birth. Affected individuals have feeding difficulties and delayed motor development, usually never achieving independent ambulation. Additional variable features include eye movement abnormalities, joint contractures, and rigid spine. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the synaptobrevin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P23763-1	1, VAMP-1A	yes
P23763-3	2
P23763-2	3, VAMP-1B

RefSeq proteins (4): NP_001284367, NP_055046, NP_058439, NP_954740 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001388	Synaptobrevin-like	Family
IPR016444	Synaptobrevin/VAMP	Family
IPR042855	V_SNARE_CC	Domain

Pfam: PF00957

UniProt features (18 total): site 4, mutagenesis site 3, topological domain 2, splice variant 2, chain 1, modified residue 1, sequence variant 1, sequence conflict 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23763-F1	75.47	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 60–61 ((microbial infection) cleavage; by c.botulinum neurotoxin type f (bont/f, botf)); 61–62 ((microbial infection) cleavage; by c.botulinum neurotoxin type d (bont/d, botd)); 68–69 ((microbial infection) cleavage; by c.botulinum neurotoxin type x (bont/x)); 78–79 ((microbial infection) cleavage; by c.botulinum neurotoxin type b (bont/b, botb))

Post-translational modifications (1): 63

Mutagenesis-validated functional residues (3):

Position	Phenotype
42	no change in susceptibility to c.botulinum bont/b, bont/d or bont/f.
48	1000-fold increase in susceptibility to c.botulinum bont/d, no change in susceptibility to bont/b or bont/f.
81	no change in susceptibility to c.botulinum bont/b, bont/d or bont/f.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5250955	Toxicity of botulinum toxin type D (botD)
R-HSA-5250981	Toxicity of botulinum toxin type F (botF)
R-HSA-5250989	Toxicity of botulinum toxin type G (botG)

MSigDB gene sets: 499 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, FXR_IR1_Q6, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, RORA1_01, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GCANCTGNY_MYOD_Q6, MODULE_64, GOBP_MEMBRANE_FUSION, GOBP_NEUROTRANSMITTER_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING

GO Biological Process (3): vesicle fusion (GO:0006906), SNARE complex assembly (GO:0035493), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): SNAP receptor activity (GO:0005484), syntaxin binding (GO:0019905), protein binding (GO:0005515)

GO Cellular Component (15): mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle membrane (GO:0030672), SNARE complex (GO:0031201), specific granule membrane (GO:0035579), neuron projection (GO:0043005), tertiary granule membrane (GO:0070821), mitochondrion (GO:0005739), endomembrane system (GO:0012505), membrane (GO:0016020), transport vesicle (GO:0030133), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotoxicity of clostridium toxins	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	3
secretory granule membrane	2
cytoplasmic vesicle	2
vesicle organization	1
vesicle-mediated transport	1
organelle membrane fusion	1
vesicle fusion	1
protein-containing complex assembly	1
transport	1
cellular process	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
SNARE binding	1
binding	1
mitochondrial membrane	1
organelle outer membrane	1
membrane	1
cell periphery	1
synaptic vesicle	1
exocytic vesicle membrane	1
membrane protein complex	1
specific granule	1
plasma membrane bounded cell projection	1
tertiary granule	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1
endomembrane system	1
vesicle membrane	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VAMP1	SNAP25	P13795	973
VAMP1	STX1A	Q16623	935
VAMP1	SNAP23	O00161	932
VAMP1	CPLX3	Q8WVH0	866
VAMP1	STX4	Q12846	858
VAMP1	STX1B	P61266	833
VAMP1	VAMP7	P51809	823
VAMP1	SYT1	P21579	809
VAMP1	CPLX4	Q7Z7G2	806
VAMP1	STX3	Q13277	792
VAMP1	STX6	O43752	781
VAMP1	STX2	P32856	770
VAMP1	TAPBPL	Q9BX59	760
VAMP1	VAPA	Q9P0L0	733
VAMP1	KIF1A	Q12756	713

IntAct

14 interactions, top by confidence:

A	B	Type	Score
VAMP1	SNAP29	psi-mi:“MI:0915”(physical association)	0.560
VAMP1	STX4	psi-mi:“MI:0915”(physical association)	0.560
VAMP1	KASH5	psi-mi:“MI:0915”(physical association)	0.560
SNAP29	VAMP1	psi-mi:“MI:0915”(physical association)	0.560
KASH5	VAMP1	psi-mi:“MI:0915”(physical association)	0.560
IKBKE	VAMP1	psi-mi:“MI:0915”(physical association)	0.400
CDKN2A	VAMP1	psi-mi:“MI:0915”(physical association)	0.370
SNAP25	STX7	psi-mi:“MI:0914”(association)	0.350
VAMP1	DNAJC5	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (56): VAMP1 (Two-hybrid), SNAP29 (Two-hybrid), CCDC155 (Two-hybrid), VAMP1 (Two-hybrid), VAMP1 (Two-hybrid), DNAJC5 (FRET), VAMP1 (Affinity Capture-RNA), VAMP1 (Two-hybrid), VAMP1 (Two-hybrid), VAMP1 (Two-hybrid), VAMP1 (Two-hybrid), VAMP1 (Two-hybrid), VAMP1 (Two-hybrid), VAMP1 (Two-hybrid), VAMP1 (Two-hybrid)

ESM2 similar proteins: O02495, O15155, O23429, O35623, O94651, O95183, P13701, P18489, P23763, P32867, P34351, P35589, P47192, P47193, P47194, P63024, P63025, P63026, P63027, P63044, P63045, P78768, P93654, Q04338, Q09730, Q0V7N0, Q15836, Q20574, Q27236, Q2KJD2, Q4R8T0, Q54GB3, Q5RBX2, Q60WU2, Q62442, Q62896, Q63666, Q6TMJ9, Q7XIE2, Q8VXX9

Diamond homologs: O02495, O48850, O49377, O70404, O70480, O75379, O95183, P13701, P18489, P23763, P31109, P33328, P34351, P35589, P47192, P47193, P47194, P63024, P63025, P63026, P63027, P63044, P63045, Q0V7N0, Q12255, Q15836, Q27236, Q2KHY2, Q2KJD2, Q32L97, Q3T0Y8, Q4R8T0, Q5REQ5, Q60WU2, Q62442, Q63666, Q6TMJ9, Q92356, Q9BV40, Q9FMR5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

11 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	5
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3256752	NM_014231.5(VAMP1):c.341-24G>A	Likely pathogenic

SpliceAI

614 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6464942:C:CC	acceptor_gain	1.0000
12:6465837:TTCAC:T	donor_loss	1.0000
12:6465839:CA:C	donor_loss	1.0000
12:6465840:A:C	donor_loss	1.0000
12:6465841:C:T	donor_loss	1.0000
12:6465865:T:TA	donor_gain	1.0000
12:6465866:C:A	donor_gain	1.0000
12:6465874:G:C	donor_gain	1.0000
12:6465997:CCAC:C	acceptor_gain	1.0000
12:6465998:CAC:C	acceptor_gain	1.0000
12:6465998:CACC:C	acceptor_gain	1.0000
12:6466001:C:CC	acceptor_gain	1.0000
12:6466222:TACCT:T	donor_loss	1.0000
12:6466223:AC:A	donor_loss	1.0000
12:6466223:ACCT:A	donor_gain	1.0000
12:6466224:CC:C	donor_loss	1.0000
12:6466224:CCTC:C	donor_gain	1.0000
12:6470528:A:AC	donor_gain	1.0000
12:6470529:C:CC	donor_gain	1.0000
12:6464938:TCAT:T	acceptor_gain	0.9900
12:6464938:TCATC:T	acceptor_loss	0.9900
12:6464939:CAT:C	acceptor_gain	0.9900
12:6464939:CATC:C	acceptor_gain	0.9900
12:6464939:CATCT:C	acceptor_loss	0.9900
12:6464940:ATC:A	acceptor_loss	0.9900
12:6464941:TC:T	acceptor_loss	0.9900
12:6464942:C:CA	acceptor_loss	0.9900
12:6464943:T:G	acceptor_loss	0.9900
12:6465909:G:A	donor_gain	0.9900
12:6465999:AC:A	acceptor_gain	0.9900

AlphaMissense

766 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6465893:A:C	F79L	0.999
12:6465893:A:T	F79L	0.999
12:6465895:A:G	F79L	0.999
12:6465894:A:C	F79C	0.998
12:6465925:C:G	A69P	0.998
12:6465873:A:G	L86P	0.997
12:6465882:G:T	A83D	0.997
12:6465894:A:G	F79S	0.997
12:6465919:C:G	A71P	0.997
12:6464917:A:G	C105R	0.996
12:6464926:C:G	G102R	0.996
12:6464926:C:T	G102R	0.996
12:6465883:C:G	A83P	0.996
12:6465927:C:G	R68P	0.996
12:6465936:A:G	L65P	0.996
12:6464925:C:T	G102E	0.995
12:6465904:C:G	A76P	0.995
12:6465945:A:G	L62P	0.995
12:6465957:C:A	R58M	0.995
12:6465910:C:G	A74P	0.994
12:6465915:A:G	L72S	0.994
12:6465924:G:T	A69D	0.994
12:6465963:A:G	L56P	0.994
12:6465956:C:A	R58S	0.993
12:6465956:C:G	R58S	0.993
12:6465901:A:G	S77P	0.992
12:6465954:T:A	D59V	0.992
12:6465977:G:C	N51K	0.992
12:6465977:G:T	N51K	0.992
12:6465984:C:G	R49P	0.991

dbSNP variants (sampled 300 via entrez): RS1000101316 (12:6465083 T>C), RS1000146139 (12:6462405 C>A), RS1000236213 (12:6469446 G>T), RS1000984180 (12:6467187 T>C), RS1001518143 (12:6469168 A>G), RS1001593270 (12:6462682 C>G,T), RS1001685370 (12:6469380 C>G), RS1001716393 (12:6469029 G>A,C), RS1002753429 (12:6470149 G>C), RS1003001207 (12:6464048 C>A,G,T), RS1003004574 (12:6463997 A>G), RS1003155929 (12:6468704 G>A), RS1004247082 (12:6470974 T>G), RS1004278404 (12:6470706 T>C), RS1004452306 (12:6467769 G>A)

Disease associations

OMIM: gene MIM:185880 | disease phenotypes: MIM:618323

GenCC curated gene-disease

Disease	Classification	Inheritance
myasthenic syndrome, congenital, 25, presynaptic	Strong	Autosomal recessive
spastic ataxia 1	Strong	Autosomal dominant
presynaptic congenital myasthenic syndrome	Supportive	Autosomal dominant

Mondo (3): myasthenic syndrome, congenital, 25, presynaptic (MONDO:0032675), spastic ataxia 1 (MONDO:0007164), (MONDO:0020345)

Orphanet (0):

HPO phenotypes

108 total (30 of 108 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000308	Microretrognathia
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000486	Strabismus
HP:0000492	Abnormal eyelid morphology
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000514	Slow saccadic eye movements
HP:0000565	Esotropia
HP:0000602	Ophthalmoplegia
HP:0000605	Supranuclear gaze palsy
HP:0000639	Nystagmus
HP:0000651	Diplopia
HP:0000768	Pectus carinatum
HP:0000961	Cyanosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001276	Hypertonia
HP:0001283	Bulbar palsy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000101_14	Hip geometry	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004685	hip geometry

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566993	Ataxia, Spastic, 1, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression, affects expression	4
Acetaminophen	affects expression, decreases expression, increases expression	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Aspirin	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TX25	HAP1 VAMP1 (-) 1	Cancer cell line	Male
CVCL_TX26	HAP1 VAMP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.