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  3. VMAT2

VMAT2 (Solute carrier family 18 (vesicular monoamine transporter), member 2 L homeolog)

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Summary of VMAT2

Vesicular monoamine transporter 2 (VMAT2) is a protein that is encoded by the SLC18A2 gene (Solute carrier family 18 member 2) in humans. VMAT2 is a member of the toxin extruding antiporter family [R].

VMAT2 is located in neurons, where it acts as a pump for neurotransmitters, packaging them to be released from the neurons. 

VMAT2 is essential for motor control, stable mood, and autonomic function [R], and protects the neurons from both internal and external toxins [R].

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Protein names

Recommended name:

Synaptic vesicular amine transporter

Short name:

VAT2

Alternative name(s):

Monoamine transporter
Solute carrier family 18 member 2
Vesicular amine transporter 2

VMAT2 SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS363227 (VMAT2) ??
  2. RS363387 (VMAT2) ??

Fixes

Manipulating VMAT2 levels or function may provide benefits for Parkinsons disease patients, protecting them from either external or internal neurotoxic insults [R].

VMAT2 may be a potential target for diabetes [R].

Estrogens prevent the loss of VMAT2 in MPTP-treated mice [R].

For people carrying VMAT2 genetic variants associated to substance abuse, environments possessing social, sensory, and motor enrichment may have a beneficial effect against relapse [R].

Advanced Summary

Vesicular monoamine transporter 2 (VMAT2) is a protein that is encoded by the SLC18A2 gene (Solute carrier family 18 member 2) in humans. VMAT2 is a member of the toxin extruding antiporter family [R].

VMAT2 is located in neurons, where it acts as a pump for neurotransmitters, packaging them to be released from the neurons [R]. These neurotransmitters include dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin, histamine and GABA [R;R].

VMAT2 is essential for motor control, stable mood, and autonomic function [R], and protects the neurons from both internal and external toxins [R].

VMAT2 additionally plays a role in the pancreas, where it regulates the production of beta cells that store and release insulin [R].

Reduced VMAT2 function leads to the loss of structure and function of neurons [R], and is linked to many clinical neurological disorders including Parkinson's Disease [R], Schizophrenia, Bipolar disorder [R], Tardive dyskinesia (TD) [R] and Posttraumatic Stress Disorder [R].

Furthermore, VMAT2 is associated with both anxiety-like behavior [R] and depression [R]. 

VMAT is also associated with METH and cocaine toxicity [R], alcohol and nicotine dependence [R;R].

VMAT2 uses energy from to package monoamines (neurotransmitters) from the neuronal cellular fluid into small sacs for their subsequent release from the neuron [R;R].

VMAT2 is produced primarily brain and histaminergic cells in the gastrointestinal (GI) tract [R].

Complete loss of VMAT2 is lethal in mice [R], while VMAT2-partially deficient mice display progressive neurodegeneration [R].

With aging, there are severe changes in the distribution and the condition of VMAT2 in rats [R].

VMAT2 was nicknamed The God GeneĀ because a variation in the VMAT2 gene supposedly plays a role in one's openness to spiritual experiences, but this association has not been confirmed in scientific studies [R].

VMAT2 and Neurotoxicity

While the primary function of VMAT2 is to sequester neurotransmitters, this transporter also provides neuroprotection from both internal and external toxicants [R] and protects against neurotoxin-induced cell death [R].

VMAT2 was originally identified by its ability to protect cells from the toxicity of the Parkinsonism-inducing dopamine neurotoxin MPP+ [R].

In mice with reduced VMAT2 function, administration of MPP+ produces more than twice the dopamine cell loss found in normal mice [R].

VMAT2-deficiency also enhances methamphetamine neurotoxicity in mice [R].

VMAT2 and Parkinsons disease

A decrease in VMAT2 production correlates with susceptibility to Parkinson's Disease (PD) [R].   

VMAT2 is dysfunctional in brains with Parkinson's disease [R].

A familial VMAT2 mutation causes an infantile parkinsonian condition with profound motor and cognitive impairments [R].

On the other hand, an increase in VMAT2 level or function protects against the development of PD [R].

Two SNPs in the promoter region of the VMAT2 gene are associated with a reduced PD risk [R], and gain-of-function VMAT2 variants confer protection from PD in women [R].

VMAT2 and other Neurological disorders

Abnormal production of VMAT2 is found in patients with epilepsy [R], and Dementia with Lewy bodies (DLB) [R].

Variations in VMAT2 may be linked to alterations in cognitive functioning underlying psychotic disorder [R].

A VMAT2 risk variant is linked to Posttraumatic Stress Disorder [R].

SNPs in VMAT2 are linked to Schizophrenia, Bipolar disorder [R;R], and Tardive dyskinesia (TD) [R].

A variation within VMAT2 is also associated with cognitive outcomes after severe traumatic brain injury TBI [R].

VMAT2 in Anxiety and Depression

VMAT2 deficiency elicits anxiety-like behavior in zebrafish [R].

VMAT2 deficient mice showed an increase in anxiety in some studies[R], while exhibiting sluggishness, listlessness, and depression [R].

VMAT2 genetic or functional alterations (deficiency) are associated with depression in rats [R], and depression symptoms in men [R].

Reserpine, an irreversible VMAT blocker, prescribed as a medication to lower blood pressure, causes depression in humans [R]. 

VMAT2 and Substance Abuse

Many psychostimulant drugs interact with VMAT2, including methamphetamine (METH), cocaine, and ecstasy (MDMA).

Deletion of VMAT2 results in super-sensitivity to cocaine and amphetamine [R].

VMAT2 inhibitors decrease self-administration of METH in rats [R;R].

On the other hand, elevated VMAT2 levels in mice protects against METH toxicity without enhancing the rewarding effects of the drug [R].

Genetic variants in VMAT2 are linked to alcohol and nicotine dependence [R;R], and certain variants regulating VMAT2 promoter activity are protective against alcoholism [R].

Loss of VMAT2 increased alcohol consumption in male mice [R].

VMAT2 and Diabetes

VMAT2 is an inhibitor of beta cell production in the pancreas [R]. Reserpine and Tetrabenazine (TBZ), both VMAT2 inhibitors, increase production of beta cells, which decreases blood glucose [R].

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