SLC18A2

solute carrier family 18 member A2, the group of Solute carrier family 18

Basic information

Region (hg38): 10:117241092-117279430

Previous symbols: [ "VMAT2" ]

Links

ENSG00000165646 ∙ NCBI:6571 ∙ OMIM:193001 ∙ HGNC:10935 ∙ Uniprot:Q05940 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• brain dopamine-serotonin vesicular transport disease (Supportive), mode of inheritance: AR
• parkinsonism-dystonia, infantile, 2 (Moderate), mode of inheritance: AR
• parkinsonism-dystonia, infantile, 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinsonism-dystonia, infantile, 2	AR	Neurologic	The condition can manifest with neurologic manifestations such as movement disorders and autonomic dysfunctiontreatment, and medical management with a dopamine receptor agonist has been described as resulting in marked clinical improvement	Neurologic	23363473

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC18A2 gene.

• not provided (141 variants)
• Inborn genetic diseases (17 variants)
• Parkinsonism-dystonia, infantile, 2 (9 variants)
• not specified (3 variants)
• Abnormal brain morphology (1 variants)
• Brain dopamine-serotonin vesicular transport disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC18A2 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				37	3	40
missense		1	49	1	3	54
nonsense			2			2
start loss						0
frameshift	2	1	1			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			5	5		10
non coding			2	19	23	44
Total	2	2	55	57	29

Highest pathogenic variant AF is 0.000118

Variants in SLC18A2

This is a list of pathogenic ClinVar variants found in the SLC18A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-117241444-G-A			Benign (May 22, 2021)
10-117241640-A-C		Parkinsonism-dystonia, infantile, 2	Benign (Jul 15, 2021)
10-117241702-G-A			Likely benign (May 14, 2018)
10-117241706-G-A			Uncertain significance (Jan 31, 2022)
10-117241713-C-T			Uncertain significance (Oct 13, 2022)
10-117241720-C-T			Likely benign (Dec 09, 2023)
10-117241721-C-G			Uncertain significance (Aug 31, 2021)
10-117241726-G-A		Parkinsonism-dystonia, infantile, 2	Uncertain significance (Dec 17, 2019)
10-117241736-AGCCGCCGCTC-A			Pathogenic (Oct 31, 2022)
10-117241738-C-A		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
10-117241742-C-T		Inborn genetic diseases	Uncertain significance (Apr 26, 2023)
10-117241744-C-G			Likely benign (May 11, 2023)
10-117241774-C-T			Likely benign (Jul 17, 2023)
10-117241786-G-A			Likely benign (Dec 13, 2023)
10-117241791-A-C			Uncertain significance (Sep 13, 2022)
10-117241800-T-C			Uncertain significance (Oct 13, 2023)
10-117241804-C-T			Likely benign (May 04, 2018)
10-117241810-C-A			Likely benign (Jun 15, 2023)
10-117241827-A-G			Likely benign (Jun 26, 2021)
10-117243797-C-G			Benign (May 15, 2021)
10-117243952-A-T			Likely benign (Jun 25, 2022)
10-117243996-C-T		SLC18A2-related disorder	Likely benign (Apr 06, 2023)
10-117244034-C-T			Benign (Aug 19, 2021)
10-117244035-G-A			Likely benign (Jan 19, 2024)
10-117244052-C-T		SLC18A2-related disorder	Benign (Feb 28, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC18A2	protein_coding	protein_coding	ENST00000298472	15	38338

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0755	0.924	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	240	301	0.797	0.0000164	3353
Missense in Polyphen		35	62.569	0.55938		653
Synonymous	-0.0253	122	122	1.00	0.00000804	1023
Loss of Function	3.42	7	25.7	0.272	0.00000124	297

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000347	0.000347
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000279	0.000277
European (Non-Finnish)	0.000134	0.000132
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Alcoholism - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Sympathetic Nerve Pathway (Neuroeffector Junction);Nicotine Activity on Dopaminergic Neurons;Synaptic Vesicle Pathway;Dopaminergic Neurogenesis;Amine compound SLC transporters;Tyrosine metabolism;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Neuronal System;Histidine metabolism;Tryptophan metabolism;Na+/Cl- dependent neurotransmitter transporters;Dopamine Neurotransmitter Release Cycle;Neurotransmitter release cycle;Transmission across Chemical Synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle (Consensus)

Recessive Scores

• pRec: 0.214

Intolerance Scores

• loftool: 0.354
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.4

Haploinsufficiency Scores

• pHI: 0.358
• hipred: Y
• hipred_score: 0.830
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.194

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc18a2
• Phenotype: taste/olfaction phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: slc18a2
• Affected structure: brain
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: response to amphetamine;neurotransmitter transport;chemical synaptic transmission;neurotransmitter secretion;locomotory behavior;post-embryonic development;aminergic neurotransmitter loading into synaptic vesicle;monoamine transport;dopamine transport;sequestering of neurotransmitter;serotonin uptake;transmembrane transport;neurotransmitter loading into synaptic vesicle;negative regulation of reactive oxygen species biosynthetic process
• Cellular component: plasma membrane;integral component of plasma membrane;synaptic vesicle;membrane;synaptic vesicle membrane;terminal bouton;clathrin-sculpted monoamine transport vesicle membrane;dopaminergic synapse
• Molecular function: serotonin:sodium symporter activity;monoamine transmembrane transporter activity