SLC18A3 (solute carrier family 18 member A3)

Gene

• Entrez ID: 6572
• Gene name: Solute carrier family 18 member A3
• Gene symbol: SLC18A3
• Synonyms (NCBI Gene): CMS21, VACHT
• Chromosome: 10
• Chromosome location: 10q11.23
• Summary: This gene is a member of the vesicular amine transporter family. The encoded transmembrane protein transports acetylcholine into secretory vesicles for release into the extracellular space. Acetylcholine transport utilizes a proton gradient established by

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1353639	hsa-miR-125a-5p	CLIP-seq
MIRT1353640	hsa-miR-125b	CLIP-seq
MIRT1353641	hsa-miR-1291	CLIP-seq
MIRT1353642	hsa-miR-1302	CLIP-seq
MIRT1353643	hsa-miR-1343	CLIP-seq
MIRT1353644	hsa-miR-296-5p	CLIP-seq
MIRT1353645	hsa-miR-3135b	CLIP-seq
MIRT1353646	hsa-miR-3689d	CLIP-seq
MIRT1353647	hsa-miR-4298	CLIP-seq
MIRT1353648	hsa-miR-4319	CLIP-seq
MIRT1353649	hsa-miR-541	CLIP-seq
MIRT1353650	hsa-miR-654-5p	CLIP-seq
MIRT1353651	hsa-miR-765	CLIP-seq
MIRT2329122	hsa-miR-1266	CLIP-seq
MIRT2329123	hsa-miR-3144-5p	CLIP-seq
MIRT2329124	hsa-miR-3191	CLIP-seq
MIRT2329125	hsa-miR-3909	CLIP-seq
MIRT2329126	hsa-miR-412	CLIP-seq
MIRT2329127	hsa-miR-4518	CLIP-seq
MIRT2329128	hsa-miR-4652-5p	CLIP-seq
MIRT2329129	hsa-miR-510	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005277	Function	Acetylcholine transmembrane transporter activity	IBA
GO:0005277	Function	Acetylcholine transmembrane transporter activity	TAS
GO:0005278	Function	Acetylcholine:proton antiporter activity	IDA	8910293, 20225888
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005886	Component	Plasma membrane	TAS
GO:0006836	Process	Neurotransmitter transport	IEA
GO:0006836	Process	Neurotransmitter transport	TAS
GO:0007268	Process	Chemical synaptic transmission	IBA
GO:0014057	Process	Positive regulation of acetylcholine secretion, neurotransmission	ISS
GO:0015311	Function	Monoamine:proton antiporter activity	IDA	25355561
GO:0016020	Component	Membrane	IEA
GO:0022857	Function	Transmembrane transporter activity	IEA
GO:0030121	Component	AP-1 adaptor complex	IBA
GO:0030122	Component	AP-2 adaptor complex	IBA
GO:0030669	Component	Clathrin-coated endocytic vesicle membrane	TAS
GO:0030672	Component	Synaptic vesicle membrane	IEA
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0043195	Component	Terminal bouton	IBA
GO:0045202	Component	Synapse	IEA
GO:0051610	Process	Serotonin uptake	IDA	25355561
GO:0051630	Process	Acetylcholine uptake	IDA	8910293, 20225888, 25355561
GO:0055085	Process	Transmembrane transport	IEA
GO:0060201	Component	Clathrin-sculpted acetylcholine transport vesicle membrane	TAS
GO:1900273	Process	Positive regulation of long-term synaptic potentiation	ISS
GO:1902600	Process	Proton transmembrane transport	IEA
GO:1904398	Process	Positive regulation of neuromuscular junction development	ISS

Other IDs

• MIM: 600336
• HGNC: 10936
• e!Ensembl: ENSG00000187714

Protein

• UniProt ID: Q16572
• Protein name: Vesicular acetylcholine transporter (VAChT) (Solute carrier family 18 member 3)
• Protein function: Electrogenic antiporter that exchanges one cholinergic neurotransmitter, acetylcholine or choline, with two intravesicular protons across the membrane of synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proto
• PDB: 8XTW, 8XTX, 8XTY, 8ZMR, 8ZMS
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07690	MFS_1	35 → 413	Major Facilitator Superfamily	Family

• Tissue specificity: TISSUE SPECIFICITY: Peripheral and central cholinergic nervous systems. {ECO:0000269|PubMed:8071310}.
• Sequence:

  MESAEPAGQARAAATKLSEAVGAALQEPRRQRRLVLVIVCVALLLDNMLYMVIVPIVPDY
  IAHMRGGGEGPTRTPEVWEPTLPLPTPANASAYTANTSASPTAAWPAGSALRPRYPTESE
  DVKIGVLFASKAILQLLVNPLSGPFIDRMSYDVPLLIGLGVMFASTVLFAFAEDYATLFA
  ARSLQGLGSAFADTSGIAMIADKYPEEPERSRALGVALAFISFGSLVAPPFGGILYEFAG
  KRVPFLVLAAVSLFDALLLLAVAKPFSAAARARANLPVGTPIHRLMLDPYIAVVAGALTT
  CNIPLAFLEPTIATWMKHTMAASEWEMGMAWLPAFVPHVLGVYLTVRLAARYPHLQWLYG
  ALGLAVIGASSCIVPACRSFAPLVVSLCGLCFGIALVDTALLPTLAFLVDVRHVSVYGSV
  YAIADISYSVAYALGPIVAGHIVHSLGFEQLSLGMGLANLLYAPVLLLLRNVGLLTRSRS
  ERDVLLDEPPQGLYDAVRLRERPVSGQDGEPRSPPGPFDACEDDYNYYYTRS

• Sequence length: 532

Pathways

KEGG:

Synaptic vesicle cycle
Cholinergic synapse

Reactome:

Acetylcholine Neurotransmitter Release Cycle
Cargo recognition for clathrin-mediated endocytosis
Clathrin-mediated endocytosis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Congenital myasthenic syndrome 21	Likely pathogenic	rs1057517666	RCV000412646	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CONGEN MYASTHENIC SYNDROMES PRESYNAPTIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FETAL AKINESIA DEFORMATION SEQUENCE	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FETAL AKINESIA DEFORMATION SEQUENCE 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HODGKINS LYMPHOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYASTHENIC SYNDROME, CONGENITAL, 21, PRESYNAPTIC	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYASTHENIC SYNDROMES, CONGENITAL	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PENA-SHOKEIR SYNDROME TYPE I	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRESYNAPTIC CONGENITAL MYASTHENIC SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRESYNAPTIC CONGENITAL MYASTHENIC SYNDROMES	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SLC18A3-related disorder	Likely benign; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	21743130	Inhibit	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Late Onset	Alzheimer disease	BEFREE	12759818		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	BEFREE	28188302, 31059209		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	GENOMICS_ENGLAND_DG	31059209		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	21948486	Associate	★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bulbar palsy	Bulbar palsy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	28931760		★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Dysplasia Of The Hip	Developmental dysplasia of the hip	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital kyphoscoliosis	Congenital kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Myasthenic Syndromes, Postsynaptic	Myasthenic Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Congenital Myasthenic Syndromes, Presynaptic	Myasthenic Syndrome	ORPHANET_DG	27590285		★☆☆☆☆ Found in Text Mining only
Congenital Myasthenic Syndromes, Presynaptic	Myasthenic Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus carinatum	Congenital Pectus Carinatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	26481308		★☆☆☆☆ Found in Text Mining only
Constipation	Constipation	Pubtator	21948486	Associate	★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Deglutition disorder	Pubtator	21948486	Associate	★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	BEFREE	28590490, 29315563		★☆☆☆☆ Found in Text Mining only
Distal amyotrophy	Distal amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	21948486	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	30126014		★☆☆☆☆ Found in Text Mining only
Esotropia	Esotropia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Facial paralysis	Facial paralysis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fetal akinesia deformation sequence	Fetal Akinesia Deformation Sequence	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastroesophageal reflux disease	Gastroesophageal Reflux Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	26481308		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	16376318, 30008624, 30274694		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lambert-Eaton Myasthenic Syndrome	Lambert-Eaton Myasthenic Syndrome	BEFREE	28188302		★☆☆☆☆ Found in Text Mining only
Learning Disabilities	Learning disorders	Pubtator	27590285	Associate	★☆☆☆☆ Found in Text Mining only
Myasthenias	Myasthenia Gravis	BEFREE	30003945		★☆☆☆☆ Found in Text Mining only
Myasthenias	Myasthenia Gravis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myasthenic Syndrome	Myasthenic Syndrome	BEFREE	28188302		★☆☆☆☆ Found in Text Mining only
Myasthenic syndrome congenital type Id	Myasthenic syndrome	Pubtator	27590285, 33462016	Associate	★☆☆☆☆ Found in Text Mining only
MYASTHENIC SYNDROME, CONGENITAL, 21, PRESYNAPTIC	Myasthenic Syndrome	UNIPROT_DG	27590285		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYASTHENIC SYNDROME, CONGENITAL, 21, PRESYNAPTIC	Myasthenic Syndrome	GENOMICS_ENGLAND_DG	27590285, 31059209		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYASTHENIC SYNDROME, CONGENITAL, 21, PRESYNAPTIC	Myasthenic Syndrome	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myasthenic Syndromes Congenital	Myasthenic syndrome	Pubtator	27590285, 33462016	Associate	★☆☆☆☆ Found in Text Mining only
Myasthenic Syndromes, Congenital	Myasthenic Syndrome	BEFREE	27590285, 28188302, 29130637, 30003945, 31059209		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myasthenic Syndromes, Congenital	Myasthenic Syndrome	GENOMICS_ENGLAND_DG	27590285		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myasthenic Syndromes, Congenital	Myasthenic Syndrome	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myasthenic Syndromes, Congenital, Slow Channel	Myasthenic Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Narcolepsy-Cataplexy Syndrome	Narcolepsy-Cataplexy Syndrome	BEFREE	20576035		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	30008624		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus Pathologic	Nystagmus	Pubtator	21948486	Associate	★☆☆☆☆ Found in Text Mining only
Ocular Albinism type 1	Ocular albinism	Pubtator	30720884	Associate	★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia	Ophthalmoplegia	Pubtator	27590285	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	28058727, 30720884		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	39344233	Associate	★☆☆☆☆ Found in Text Mining only
Pena-Shokeir syndrome type I	Pena Shokeir syndrome	BEFREE	31059209		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pena-Shokeir syndrome type I	Pena Shokeir syndrome	ORPHANET_DG	31059209		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polyneuropathy, Motor	Polyneuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	BEFREE	28590490		★☆☆☆☆ Found in Text Mining only
Presynaptic congenital myasthenic syndromes	Myasthenic Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	27825347	Associate	★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	BEFREE	28188302		★☆☆☆☆ Found in Text Mining only
Rett Syndrome	Rett Syndrome	BEFREE	22223404		★☆☆☆☆ Found in Text Mining only
Rett Syndrome	Rett syndrome	Pubtator	22223404	Associate	★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Apnea Syndromes	Sleep apnea	Pubtator	21948486	Associate	★☆☆☆☆ Found in Text Mining only
Sleep Apnea, Central	Sleep Apnea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Apnea, Obstructive	Sleep Apnea	BEFREE	24732660		★☆☆☆☆ Found in Text Mining only
Sleep Apnea, Obstructive	Sleep Apnea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	32691230	Associate	★☆☆☆☆ Found in Text Mining only
Status Epilepticus	Status Epilepticus	BEFREE	30126014		★☆☆☆☆ Found in Text Mining only
Sudden episodic apnea	Sudden episodic apnea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tourette Syndrome	Tourette syndrome	Pubtator	28791334	Associate	★☆☆☆☆ Found in Text Mining only
Varicosity	Vulval varices	BEFREE	10820203, 31766245		★☆☆☆☆ Found in Text Mining only
Ventricular Dysfunction Left	Ventricular dysfunction	Pubtator	27590285	Associate	★☆☆☆☆ Found in Text Mining only