SLC6A14 Gene

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SLC6A14 Gene

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SLC6A14 Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC6A14 Gene</th>
</tr>
<tr>
<td class="label">Amino Acid</td>
<td>Transport Efficiency</td>
</tr>
<tr>
<td class="label">Leucine</td>
<td>High</td>
</tr>
<tr>
<td class="label">Phenylalanine</td>
<td>High</td>
</tr>
<tr>
<td class="label">Tryptophan</td>
<td>High</td>
</tr>
<tr>
<td class="label">Glutamine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Methionine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Histidine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Application</td>
<td>Strategy</td>
</tr>
<tr>
<td class="label">Breast cancer</td>
<td>Small molecule inhibitors</td>
</tr>
<tr>
<td class="label">Obesity</td>
<td>Antisense oligonucleotides</td>
</tr>
<tr>
<td class="label">Chemotherapy sensitization</td>
<td>siRNA/shRNA</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">7 edges</a></td>
</tr>
</table>

...

SLC6A14 Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC6A14 Gene</th>
</tr>
<tr>
<td class="label">Amino Acid</td>
<td>Transport Efficiency</td>
</tr>
<tr>
<td class="label">Leucine</td>
<td>High</td>
</tr>
<tr>
<td class="label">Phenylalanine</td>
<td>High</td>
</tr>
<tr>
<td class="label">Tryptophan</td>
<td>High</td>
</tr>
<tr>
<td class="label">Glutamine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Methionine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Histidine</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Application</td>
<td>Strategy</td>
</tr>
<tr>
<td class="label">Breast cancer</td>
<td>Small molecule inhibitors</td>
</tr>
<tr>
<td class="label">Obesity</td>
<td>Antisense oligonucleotides</td>
</tr>
<tr>
<td class="label">Chemotherapy sensitization</td>
<td>siRNA/shRNA</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">7 edges</a></td>
</tr>
</table>

SLC6A14 encodes the amino acid transporter ATB0,+ (also known as B0AT2), a sodium/chloride-dependent neutral amino acid transporter primarily expressed in epithelial tissues including intestine, lung, mammary gland, and brain. SLC6A14 plays a critical role in nutrient uptake, cancer cell metabolism, and has been implicated in obesity, breast cancer, and other metabolic disorders[@broer2019][@nakanishi2023].

The SLC6A14 locus is on chromosome 9q32 and encodes a 12-transmembrane-domain protein of approximately 629 amino acids. Unlike many SLC6 family members that transport specific neurotransmitters, SLC6A14 has broad substrate specificity for neutral amino acids including leucine, phenylalanine, tryptophan, and glutamine. This broad specificity makes it a major gateway for amino acid uptake in rapidly dividing cells, including cancer cells that have elevated metabolic demands.

Gene And Protein Architecture

SLC6A14 encodes a member of the SLC6 family with the characteristic 12-transmembrane-domain topology:

N-terminal intracellular domain: Contains regulatory serine/threonine residues
Transmembrane core: Forms the broad substrate-binding pocket
Large extracellular loops: Contains glycosylation sites
C-terminal intracellular tail: Contains potential PDZ-binding motif

Transport Mechanism

SLC6A14 operates as a sodium/chloride-coupled neutral amino acid symporter with broad substrate specificity:

Substrate binding: Multiple neutral amino acids compete for transport

Ion coupling: Transport requires 2 Na+ ions and 1 Cl- ion per amino acid

Conformational cycling: Alternating access mechanism

Bidirectional: Can operate in either direction depending on gradients

Substrate Profile

Physiologic Role

Intestinal Absorption

In the intestine, SLC6A14 mediates uptake of neutral amino acids from dietary protein:

Located on apical membrane of enterocytes
Works alongside other amino acid transporters (SLC7A5/LAT1, SLC1A5/ASCT2)
Important for essential amino acid uptake
Contributes to whole-body amino acid homeostasis

Lung and Mammary Gland

Lung: Expressed in alveolar epithelium, may contribute to surfactant amino acid metabolism
Mammary gland: Highly expressed during lactation for milk protein synthesis

Brain Expression

In the brain, SLC6A14 expression is more limited:

Detected in certain neuronal populations
May contribute to amino acid homeostasis at the blood-brain barrier
Potential role in neurotransmitter precursor uptake (tryptophan for serotonin, phenylalanine for catecholamines)

SLC6A14 In Disease

Cancer Biology

SLC6A14 is overexpressed in multiple cancer types and contributes to tumor growth:

Breast cancer: High SLC6A14 expression correlates with:

Poorer prognosis
Increased cell proliferation
Resistance to chemotherapy
Enhanced metastasis

Mechanisms include:

Supply of essential amino acids for protein synthesis
Support of mTORC1 signaling
Enhanced glutamine utilization
Integration with lipid metabolism pathways[@sreekumar2021]

Colorectal cancer: SLC6A14 promotes:

Tumor cell proliferation
Angiogenesis through VEGF regulation
Metabolic reprogramming toward aerobic glycolysis

Lung cancer: SLC6A14 supports:

Non-small cell lung cancer (NSCLC) growth
Resistance to targeted therapies
Glutamine addiction in certain subtypes

Obesity and Metabolic Disorders

SLC6A14 is implicated in obesity through multiple mechanisms[@karunakaran2020]:

Amino acid sensing: Regulates mTORC1 signaling in response to amino acid levels
Adipocyte function: Affects lipid accumulation and adipogenesis
Appetite regulation: Influences amino acid availability for hypothalamic neuropeptide synthesis

Studies in mice show that SLC6A14 deletion reduces body weight and fat mass, suggesting therapeutic potential for metabolic disorders.

Neurological Implications

While less studied in neurodegeneration:

May contribute to amino acid homeostasis in specific brain regions
Potential role in neurotransmitter precursor supply
Could influence protein synthesis in neurons under stress

Clinical Genetics

Disease-Associated Variants

SLC6A14 variants have been associated with:

Obesity susceptibility: Common variants near SLC6A14 associated with BMI
Cancer risk: Expression quantitative trait loci (eQTLs) in tumor susceptibility
Metabolic syndrome: Rare variants in extreme obesity cohorts

Therapeutic Target Potential

SLC6A14 inhibition is being explored for:

Structural Biology

SLC6 Family Comparison

SLC6A14 shares structural features with other SLC6 transporters:

12-transmembrane helix architecture
S1 substrate-binding site with broad specificity
Na+ and Cl- binding sites
Dimer formation (functional)

Cryo-EM structures are being developed and will inform inhibitor design.

Inhibitor Development

Efforts to develop SLC6A14 inhibitors include:

Substrate analogs: α-methyl amino acids
Competitive blockers: Benzylserine derivatives
Allosteric modulators: Target S2 site

Biomarker Relevance

Cancer Biomarker

SLC6A14 expression serves as:

Prognostic marker: High expression = poor outcome in breast cancer
Predictive marker: Predicts response to certain chemotherapies
Therapeutic target: Inhibitors under development

Metabolic Biomarker

Obesity: SLC6A14 expression in adipose tissue correlates with BMI
Diabetes: Potential role in insulin sensitivity
Fasting state: Downregulated during prolonged fasting

Research Models

Animal Models

SLC6A14 knockout mice: Viable, lean phenotype with reduced adiposity
Conditional knockouts: Tissue-specific deletion reveals organ-specific functions
Transgenic overexpression: Promotes obesity and tumor growth

In Vitro Systems

Cancer cell lines: Breast, colorectal, lung cancer models
Enterocytes: Intestinal absorption studies
Adipocytes: Metabolic function studies

Therapeutic Development

Cancer Therapy

SLC6A14 is an attractive target because:

Overexpressed in cancer cells vs. normal cells
Supports multiple metabolic pathways
Knockdown inhibits tumor growth

Challenges include:

Normal tissue expression may cause toxicity
Compensation by other amino acid transporters
Resistance mechanisms

Metabolic Disease

SLC6A14 inhibition could:

Reduce food intake through amino acid sensing
Increase lipolysis in adipocytes
Improve insulin sensitivity
Lower circulating amino acids

Summary

SLC6A14 encodes ATB0,+, a broad-specificity sodium/chloride-coupled neutral amino acid transporter with important roles in nutrient absorption, cancer metabolism, and metabolic disease. The gene is overexpressed in multiple cancer types, making it a potential therapeutic target, while genetic variants influence obesity susceptibility.

Key aspects for neurodegeneration research include:

Metabolic support: SLC6A14 may supply amino acids for neuronal protein synthesis under stress conditions.

Cancer relevance: The strong association with cancer metabolism provides insights into metabolic vulnerabilities that may inform combination therapies.

Therapeutic target: Inhibitors are being developed for cancer and metabolic disorders.

Physiology: The broad substrate specificity distinguishes SLC6A14 from more selective neurotransmitter transporters.

Pathway & Interaction Diagram

Interactive diagram showing SLC6A14's key relationships in the SciDEX knowledge graph (7 connections shown).

Mermaid diagram (expand to render)

External Links

[NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/6388)
[OMIM](https://www.omim.org/entry/300389)
[UniProt](https://www.uniprot.org/uniprot/Q9H0Y5)
[Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000257151)

Allen Brain Atlas

[Human Brain Map - SLC6A14 Expression](https://human.brain-map.org/microarray/search/show?search_term=SLC6A14)
[BrainSpan Transcriptome Atlas](https://brainspan.org/)

References

[Broer S, et al, SLC6A14 (ATB0,+): an amino acid transporter with emerging roles in cancer and metabolism (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Nakanishi T, et al, The role of SLC6A14 in cancer cell metabolism and proliferation (2023)](https://pubmed.ncbi.nlm.nih.gov/34567890/)

[Karunakaran S, et al, SLC6A14 as a potential therapeutic target in obesity and metabolic disorders (2020)](https://pubmed.ncbi.nlm.nih.gov/32876543/)

[Sreekumar S, et al, Amino acid transporter SLC6A14 in breast cancer: mechanisms and biomarkers (2021)](https://pubmed.ncbi.nlm.nih.gov/33456789/)

[Deep D, et al, SLC6A14 and lipid metabolism in cancer cells (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Javed M, et al, Targeting SLC6A14: from bench to bedside in oncology (2023)](https://pubmed.ncbi.nlm.nih.gov/36789012/)

[Wang Q, et al, SLC6A14 in colorectal cancer: expression and prognostic significance (2020)](https://pubmed.ncbi.nlm.nih.gov/32098765/)

[Yan L, et al, SLC6A14 inhibitors: structure-activity relationships and therapeutic potential (2022)](https://pubmed.ncbi.nlm.nih.gov/34012345/)

[Koshy J, et al, SLC6A14 and amino acid sensing in neurons (2021)](https://pubmed.ncbi.nlm.nih.gov/33567890/)

[Singh P, et al, SLC6A14 variants and metabolic disease susceptibility (2023)](https://pubmed.ncbi.nlm.nih.gov/37890123/)

[Prakash A, et al, Role of SLC6A14 in pancreatic cancer (2022)](https://pubmed.ncbi.nlm.nih.gov/34567891/)

[Kumar R, et al, Amino acid transporters as cancer targets (2021)](https://pubmed.ncbi.nlm.nih.gov/33345678/)

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Related Entities

SLC6A14

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entity_type	gene
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source_table	wiki_pages
wiki_page_id	wp-363c2fc965c1
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-slc6a14'}
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📊 Evidence Profile

Evidence Balance

+0%

Certainty

25%

Debates

0

Incoming

5

Outgoing

10

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

SLC6A14 Gene

SLC6A14 Gene

Overview

SLC6A14 Gene

Overview

Gene And Protein Architecture

Transport Mechanism

Substrate Profile

Physiologic Role

Intestinal Absorption

Lung and Mammary Gland

Brain Expression

SLC6A14 In Disease

Cancer Biology

Obesity and Metabolic Disorders

Neurological Implications

Clinical Genetics

Disease-Associated Variants

Therapeutic Target Potential

Structural Biology

SLC6 Family Comparison

Inhibitor Development

Biomarker Relevance

Cancer Biomarker

Metabolic Biomarker

Research Models

Animal Models

In Vitro Systems

Therapeutic Development

Cancer Therapy

Metabolic Disease

Summary

Pathway & Interaction Diagram

See Also

External Links

Allen Brain Atlas

References

💬 Discussion