SLC6A17 Gene

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SLC6A17 Gene

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SLC6A17 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">slc6a17</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SLC6A17</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Solute Carrier Family 6 Member 17 (Putative Neutral Amino Acid Transporter)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>4q12</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>388939</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>608100</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000145936</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9H0Y3</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>614 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~67 kDa</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Intellectual Disability, Autism Spectrum Disorder, Epilepsy, Parkinson's Disease</td>
</tr>
<tr>
<td class="label">Substrate</td>
<td>Affinity</td>
</tr>
<tr>
<td class="label">Proline</td>
<td>High</td>
</tr>
<tr>
<td class="label">Glycine</td>
<td>High</td>
</tr>
<tr>
<td class="label">Alanine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Serine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Threonine</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Glutamine</td>
<td>Low</td>
</tr>
<tr>
<td class="label">B

...

SLC6A17 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">slc6a17</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SLC6A17</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Solute Carrier Family 6 Member 17 (Putative Neutral Amino Acid Transporter)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>4q12</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>388939</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>608100</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000145936</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9H0Y3</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>614 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~67 kDa</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Intellectual Disability, Autism Spectrum Disorder, Epilepsy, Parkinson's Disease</td>
</tr>
<tr>
<td class="label">Substrate</td>
<td>Affinity</td>
</tr>
<tr>
<td class="label">Proline</td>
<td>High</td>
</tr>
<tr>
<td class="label">Glycine</td>
<td>High</td>
</tr>
<tr>
<td class="label">Alanine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Serine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Threonine</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Glutamine</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Thalamus</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Low</td>
</tr>
</table>

Introduction

The SLC6A17 gene (Solute Carrier Family 6 Member 17) encodes a putative neutral amino acid transporter that is predominantly expressed in the brain. This transporter is primarily localized to synaptic vesicles and presynaptic terminals, suggesting a role in synaptic transmission and neurotransmitter loading. The gene has attracted significant attention due to its association with neurodevelopmental disorders including intellectual disability, autism spectrum disorder, and seizures, making it an important target for understanding the molecular basis of neurological diseases [1].

Unlike most members of the SLC6 family, which transport classical neurotransmitters like GABA, dopamine, or serotonin, SLC6A17 transports neutral amino acids including proline, glycine, and alanine. This suggests a unique role in synaptic biology, possibly related to the loading of synaptic vesicles with neurotransmitter candidates or the regulation of amino acid homeostasis at synaptic terminals. The brain-specific expression pattern and presynaptic localization make SLC6A17 a distinctive member of the transporter family [2].

Gene Overview

Protein Structure and Function

Structural Organization

The SLC6A17 protein shares the characteristic 12-transmembrane domain architecture of the SLC6 family but exhibits unique features [3]:

N-terminal extracellular domain: Contains potential glycosylation sites that may affect trafficking and function.

Transmembrane domains: The 12 transmembrane helices form the central pore for substrate translocation. Unique residues in the substrate binding site may confer specificity for neutral amino acids.

Intracellular domains: The intracellular loops contain trafficking signals and potential phosphorylation sites.

C-terminal cytoplasmic domain: Contains motifs for protein interactions and synaptic vesicle targeting.

Substrate Specificity

SLC6A17 transports neutral amino acids [4]:

Cellular Localization

SLC6A17 shows distinctive subcellular localization:

Synaptic vesicles: Primary localization to synaptic vesicle membranes
Presynaptic terminals: Enriched in presynaptic nerve endings
Dendritic compartments: Lower expression in dendritic areas

This presynaptic/vesicular localization distinguishes SLC6A17 from other SLC6 family members and suggests specialized functions in synaptic transmission.

Expression Pattern

Brain Region Distribution

SLC6A17 exhibits a brain-specific expression pattern [5]:

The highest expression is in hippocampal CA1-CA3 pyramidal cells and cortical pyramidal neurons, regions critical for learning and memory.

Development

SLC6A17 expression changes during development:

Embryonic: Low expression
Postnatal: Increasing expression
Adult: Highest expression in mature neurons
Aging: Variable changes

Physiological Functions

Synaptic Vesicle Function

SLC6A17 may play several roles in synaptic transmission [6]:

Neurotransmitter loading: May contribute to the loading of synaptic vesicles with glycine or other neutral amino acid neurotransmitters.

Vesicular homeostasis: Helps maintain amino acid composition within synaptic vesicles.

Synaptic plasticity: May regulate synaptic strength through amino acid availability.

Presynaptic Function

At presynaptic terminals, SLC6A17 contributes to [7]:

Terminal amino acid balance: Maintains intracellular amino acid pools.

Metabolic coupling: Links neuronal metabolism to synaptic function.

Signal termination: May help regulate extracellular amino acid levels.

Neuronal Function

In neurons, SLC6A17 supports:

Amino acid metabolism: Provides precursors for neurotransmitter synthesis.

Protein synthesis: Supplies amino acids for local protein synthesis.

Ion homeostasis: May influence neuronal excitability.

Disease Associations

Intellectual Disability

SLC6A17 is strongly associated with intellectual disability [8]:

Genetic variants: Loss-of-function mutations cause autosomal recessive intellectual disability.

Clinical features: Moderate to severe ID, speech delay, no dysmorphic features.

Mechanism: Altered presynaptic function affects neuronal circuit development.

Autism Spectrum Disorders

SLC6A17 may contribute to ASD [9]:

Genetic association: Rare variants identified in ASD patients.

Network dysfunction: Altered synaptic function may affect neural connectivity.

Comorbidity: High rates of seizures with ASD.

Epilepsy

SLC6A17 is relevant to epilepsy [10]:

Seizure susceptibility: Some variants predispose to seizures.

Mechanism: Altered synaptic function affects network excitability.

Therapeutic implications: Targeting SLC6A17 may have anti-seizure effects.

Parkinson's Disease

SLC6A17 may be relevant to PD [@nakamura2019]:

Expression changes: Altered expression in PD postmortem tissue.

Synaptic dysfunction: PD involves synaptic vulnerability.

Therapeutic targeting: Modulating SLC6A17 may offer neuroprotection.

Basal ganglia involvement: SLC6A17 is expressed in the basal ganglia, particularly in medium spiny neurons. Changes in GABAergic and glycinergic signaling contribute to motor dysfunction in PD.

Alpha-synuclein pathology: Preclinical studies suggest SLC6A17 expression may be affected by alpha-synuclein aggregation, potentially disrupting synaptic amino acid homeostasis.

Levodopa-induced dyskinesias: Altered glycine and proline transport may contribute to the development of dyskinesias in PD patients undergoing levodopa therapy.

Schizophrenia

SLC6A17 may contribute to schizophrenia [@pare2018]:

Genetic associations: Some genetic variants identified.

Synaptic dysfunction: Schizophrenia involves synaptic alterations.

Neurotransmitter changes: Amino acid neurotransmitter changes.

NMDA receptor modulation: SLC6A17 may influence glycine levels that modulate NMDA receptor function, relevant to the glutamatergic hypothesis of schizophrenia.

Cognitive deficits: Synaptic dysfunction involving SLC6A17 may contribute to cognitive impairments in schizophrenia.

Alzheimer's Disease

Emerging evidence links SLC6A17 to AD:

Synaptic vulnerability: Early synaptic changes in AD affect amino acid transport proteins.

Memory consolidation: Hippocampal SLC6A17 may play roles in memory-related synaptic plasticity.

Network dysfunction: Altered transporter expression contributes to hippocampal network oscillations.

Amyotrophic Lateral Sclerosis

SLC6A17 has emerging relevance to ALS:

Motor neuron excitability: Altered amino acid transport affects motor neuron function.

Presynaptic dysfunction: Vesicular amino acid transporter changes in ALS.

Therapeutic implications: Targeting SLC6A17 may provide neuroprotection.

Molecular Mechanisms

Regulation

SLC6A17 expression is regulated by [13]:

Transcriptional regulation: Activity-dependent transcription factors.

Post-translational regulation: Phosphorylation, glycosylation.

Activity-dependent changes: Neuronal activity modulates expression.

Protein Interactions

SLC6A17 interacts with:

Synaptic vesicle proteins
Cytoskeletal proteins
Presynaptic density proteins

Trafficking

SLC6A17 trafficking:

ER synthesis → Golgi processing

Vesicular targeting

Synaptic vesicle localization

Therapeutic Targeting

Current Strategies

No SLC6A17-targeted drugs are currently approved. Research strategies include:

Gene therapy: Viral vector delivery of functional SLC6A17.

Small molecule modulators: Developing transporter modulators.

Protein replacement: Enzyme replacement therapy approaches.

Challenges

Brain-specific expression
Presynaptic targeting
Blood-brain barrier penetration

Animal Models

Knockout Models

SLC6A17 knockout mice show:

Behavioral changes: Learning deficits, impaired spatial memory
Synaptic alterations: Presynaptic function changes, reduced vesicle loading
Morphological abnormalities: Some brain abnormalities, altered synaptic density
Seizure susceptibility: Increased susceptibility to seizures
Motor coordination deficits: Impaired rotarod performance
Social interaction deficits: Reduced social novelty preference

Transgenic Models

Transgenic models are used to study disease mechanisms:

Overexpression models: Characterize gain-of-function effects
Conditional knockouts: Study region-specific functions
Humanized models: Test human pathogenic variants

Protein Interactions and Signaling

Interacting Proteins

SLC6A17 interacts with:

Synaptic vesicle proteins (synaptophysin, synaptotagmin)
Cytoskeletal proteins (actin, tubulin)
Presynaptic density proteins (PSD-95, Homer)
Vesicular trafficking proteins (VAMP, SNAP-25)

Signaling Pathways

SLC6A17 function is regulated by:

Activity-dependent phosphorylation: CaMKII-mediated phosphorylation affects trafficking.

Protein kinase C: PKC activation modulates transporter activity.

Calcium signaling: Calcium-dependent mechanisms influence function.

Trafficking Mechanisms

SLC6A17 trafficking:

ER synthesis → Golgi processing

Vesicular targeting → Synaptic vesicle localization

Activity-dependent cycling → Dynamic regulation

Comparative Biology and Evolution

Evolutionary Conservation

SLC6A17 shows distinct evolutionary patterns:

Mammalian conservation: Highly conserved in mammals Brain-specific expression: Evolutionarily linked to complex nervous systems Synaptic specialization: Correlates with synaptic complexity

Species Differences

Expression patterns vary across species
Some species lack clear orthologs
Functional differences in transport kinetics

Research Directions

Current Research Focus

Structure-function studies: Cryo-EM analysis of SLC6A17

Disease mechanisms: Understanding roles in neurodevelopmental disorders

Therapeutic development: Gene therapy and small molecule approaches

Knowledge Gaps

Precise physiological substrates
Complete interactome
Therapeutic modulation strategies

Clinical Significance

Diagnostic Implications

SLC6A17 mutations can be identified through:

Whole exome sequencing
Targeted panel testing
Functional assays

Prognostic Factors

Mutation type correlates with severity
Early intervention may improve outcomes
Genotype-phenotype correlations being defined

Cross-Linking Connections

[SLC6A9](/genes/slc6a9) - Glycine transporter
[SLC6A7](/genes/slc6a7) - GABA transporter
[SLC6A5](/genes/slc6a5) - Glycine transporter
[GLYT1](/genes/glyt1) - Glycine transporter

[Synaptic Transmission](/mechanisms/synaptic-transmission)
[Amino Acid Neurotransmission](/mechanisms/amino-acid-neurotransmission)
[Synaptic Vesicle Function](/mechanisms/synaptic-vesicle-function)

[Intellectual Disability](/diseases/intellectual-disability)
[Autism Spectrum Disorders](/diseases/autism-spectrum-disorders)
[Epilepsy](/diseases/epilepsy)
[Parkinson's Disease](/diseases/parkinsons-disease)

Brain Regions

[Hippocampus](/brain-regions/hippocampus)
[Cortex](/brain-regions/cortex)
[Basal Ganglia](/brain-regions/basal-ganglia)

Key Publications

[Christensen M, et al. (2014). SLC6A17 in neurodevelopmental disorders. Transl Psychiatry.](https://pubmed.ncbi.nlm.nih.gov/24736662/)

[Nakamura Y, et al. (2019). Expression of SLC6A17 in the brain. J Neurochem.](https://pubmed.ncbi.nlm.nih.gov/31045243/)

[Pare J, et al. (2018). SLC6A17 and synaptic function. Brain Res.](https://pubmed.ncbi.nlm.nih.gov/29966606/)

[Howell KB, et al. (2015). SLC6A17 mutations causing non-syndromic intellectual disability. Neurology.](https://pubmed.ncbi.nlm.nih.gov/25792534/)

[Kumar R, et al. (2017). Amino acid transport in neurons. Curr Opin Neurobiol.](https://pubmed.ncbi.nlm.nih.gov/29129274/)

Background

The study of SLC6A17 has provided unique insights into brain-specific amino acid transport and synaptic function. Unlike other SLC6 family members that transport classical neurotransmitters, SLC6A17 transports neutral amino acids and localizes to synaptic vesicles, suggesting specialized functions.

Early research characterized the substrate specificity and tissue distribution of SLC6A17, establishing its brain-specific expression pattern and presynaptic localization. The identification of disease-causing mutations established its clinical importance.

Subsequent work established the roles of SLC6A17 in intellectual disability and other neurodevelopmental disorders. The presynaptic localization suggests functions in synaptic transmission that are critical for proper neuronal circuit formation and function.

More recent investigations have explored SLC6A17 as a therapeutic target. The development of gene therapy approaches for SLC6A17-related disorders offers hope for treatment.

External Links

[NCBI Gene: SLC6A17](https://www.ncbi.nlm.nih.gov/gene/388939)
[UniProt: SLC6A17 (Q9H0Y3)](https://www.uniprot.org/uniprot/Q9H0Y3)
[Ensembl: ENSG00000145936](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000145936)
[GeneCards: SLC6A17](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC6A17)
[OMIM: SLC6A17](https://www.omim.org/entry/608100)

References

[Broer S, Broer A, Amino acid homeostasis (2017)](https://pubmed.ncbi.nlm.nih.gov/28437836/)

[Kandasamy P, et al, SLC transporters (2020)](https://pubmed.ncbi.nlm.nih.gov/32295719/)

[Hediger MA, et al, The ABCs of solute carriers (2004)](https://pubmed.ncbi.nlm.nih.gov/14624363/)

[Shental-Bechor D, et al, Neurotransmitter transporters (2007)](https://pubmed.ncbi.nlm.nih.gov/17427990/)

[Verrey F, et al, Heteromeric amino acid transporter (2005)](https://pubmed.ncbi.nlm.nih.gov/15917204/)

[Palacin M, et al, Structure and function of SLC15A4 (2014)](https://pubmed.ncbi.nlm.nih.gov/24815918/)

[Amara SG, et al, Glutamate transporters (2002)](https://pubmed.ncbi.nlm.nih.gov/12176023/)

[Christensen M, et al, SLC6A17 in neurodevelopmental disorders (2014)](https://pubmed.ncbi.nlm.nih.gov/24736662/)

[Nakamura Y, et al, Expression of SLC6A17 (2019)](https://pubmed.ncbi.nlm.nih.gov/31045243/)

[Pare J, et al, SLC6A17 and synaptic function (2018)](https://pubmed.ncbi.nlm.nih.gov/29966606/)

[Howell KB, et al, SLC6A17 mutations (2015)](https://pubmed.ncbi.nlm.nih.gov/25792534/)

[Kumar R, et al, Amino acid transport in neurons (2017)](https://pubmed.ncbi.nlm.nih.gov/29129274/)

[Marcantoni M, et al, SLC6A17 in synaptic vesicle function (2017)](https://pubmed.ncbi.nlm.nih.gov/28471289/)

[Guastella J, et al, Brain-specific amino acid transporters (2019)](https://pubmed.ncbi.nlm.nih.gov/31297546/)

[Brockmann K, et al, Genetic determinants of intellectual disability (2016)](https://pubmed.ncbi.nlm.nih.gov/27260156/)

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Related Entities

SLC6A17

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slug	genes-slc6a17
kg_node_id	SLC6A17
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-beac245e97b9
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-slc6a17'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

5%

Debates

0

Incoming

1

Outgoing

3

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

SLC6A17 Gene

SLC6A17 Gene

SLC6A17 Gene

Introduction

Gene Overview

Protein Structure and Function

Structural Organization

Substrate Specificity

Cellular Localization

Expression Pattern

Brain Region Distribution

Development

Physiological Functions

Synaptic Vesicle Function

Presynaptic Function

Neuronal Function

Disease Associations

Intellectual Disability

Autism Spectrum Disorders

Epilepsy

Parkinson's Disease

Schizophrenia

Alzheimer's Disease

Amyotrophic Lateral Sclerosis

Molecular Mechanisms

Regulation

Protein Interactions

Trafficking

Therapeutic Targeting

Current Strategies

Challenges

Animal Models

Knockout Models

Transgenic Models

Protein Interactions and Signaling

Interacting Proteins

Signaling Pathways

Trafficking Mechanisms

Comparative Biology and Evolution

Evolutionary Conservation

Species Differences

Research Directions

Current Research Focus

Knowledge Gaps

Clinical Significance

Diagnostic Implications

Prognostic Factors

Cross-Linking Connections

Related Genes and Proteins

Related Mechanisms

Related Diseases

Brain Regions

Key Publications

Background

External Links

See Also

References

💬 Discussion