Details for: SLC38A5

Gene ID: 92745

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SLC38A5

Ensembl ID: ENSG00000017483

Description: solute carrier family 38 member 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • blood vessel endothelial cell CL0000071
    CSI 26.93
    rCSI 55.87%
    PRS 88.32
  • cerebral cortex endothelial cell CL1001602
    CSI 12.3
    rCSI 21.27%
    PRS 84.65
  • plasmacytoid dendritic cell, human CL0001058
    CSI 7.33
    rCSI 5.12%
    PRS 93.06
  • retinal blood vessel endothelial cell CL0002585
    CSI 6.88
    rCSI 10.98%
    PRS 92.37
  • plasmablast CL0000980
    CSI 6.48
    rCSI 5.1%
    PRS 92.43
  • fibroblast of lung CL0002553
    CSI 4.6
    rCSI 4.28%
    PRS 91.3
  • bronchus fibroblast of lung CL2000093
    CSI 4.59
    rCSI 3.73%
    PRS 89.41
  • brain vascular cell CL4023072
    CSI 4.28
    rCSI 44.29%
    PRS 84.39
  • pancreatic acinar cell CL0002064
    CSI 3.98
    rCSI 5.3%
    PRS 92.93
  • erythrocyte CL0000232
    CSI 3.52
    rCSI 7.99%
    PRS 88.48
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.4
    rCSI 3.72%
    PRS 91.54
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.31
    rCSI 2.86%
    PRS 92.15
  • IgA plasma cell CL0000987
    CSI 2.96
    rCSI 3.03%
    PRS 92.07
  • primitive red blood cell CL0002355
    CSI 2.95
    rCSI 15.89%
    PRS 92.07
  • IgG plasma cell CL0000985
    CSI 2.54
    rCSI 3.04%
    PRS 94.05
  • keratinocyte CL0000312
    CSI 2.5
    rCSI 2.1%
    PRS 90.5
  • colon epithelial cell CL0011108
    CSI 2.5
    rCSI 2.62%
    PRS 87.76
  • adventitial cell CL0002503
    CSI 2.4
    rCSI 5.73%
    PRS 92.33
  • erythroblast CL0000765
    CSI 2.35
    rCSI 6.24%
    PRS 91.37
  • intestinal epithelial cell CL0002563
    CSI 2.35
    rCSI 2.45%
    PRS 87.64
  • transit amplifying cell of colon CL0009011
    CSI 2.32
    rCSI 2.73%
    PRS 90.14
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.26
    rCSI 2.04%
    PRS 88.81
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 2.21
    rCSI 1.47%
    PRS 95.49
  • pericyte CL0000669
    CSI 1.59
    rCSI 4.25%
    PRS 67.36
  • retinal cone cell CL0000573
    CSI 1.58
    rCSI 2.54%
    PRS 82.39
  • erythroid progenitor cell CL0000038
    CSI 1.49
    rCSI 8.53%
    PRS 92.14
  • basal cell of epidermis CL0002187
    CSI 1.48
    rCSI 2.63%
    PRS 61.16
  • erythroid lineage cell CL0000764
    CSI 1.44
    rCSI 9.25%
    PRS 93.11
  • peptic cell CL0000155
    CSI 0.48
    rCSI 4.7%
    PRS 94.13

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SLC38A5](/details-gene/92745) encodes Solute Carrier Family 38 Member 5, a sodium-dependent neutral amino acid transporter localized to the plasma membrane. This protein plays a crucial role in cellular metabolism by facilitating the transport of several amino acids, including glutamine, asparagine, serine, and glycine. **Overall**, expression data reveals that [SLC38A5](/details-gene/92745) is a highly significant marker for endothelial cells, particularly those of the central nervous system such as [cerebral cortex endothelial cell](/details-cell/CL1001602), suggesting a key function in maintaining the integrity of the blood-brain barrier. It is also prominently expressed in specific immune subsets like [plasmablast](/details-cell/CL0000980) and [plasmacytoid dendritic cell, human](/details-cell/CL0001058), indicating a role in specialized metabolic support for immune functions. Clinically, mutations in this gene have been associated with X-linked intellectual disability ([153245](https://omim.org/entry/300649)). ## Cellular Roles and Expression Landscape The expression profile of [SLC38A5](/details-gene/92745) highlights its specialized role in distinct cellular lineages, primarily within the vasculature and the immune system. **Overall**, the gene's most significant expression is observed in the vascular endothelium. It is the top marker in [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 26.93) and shows profound significance in [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 12.30) and [retinal blood vessel endothelial cell](/details-cell/CL0002585) (CSI: 6.88). This strong and specific expression pattern in the brain vasculature is consistent with its annotated role in transport across the blood-brain barrier, where it likely regulates the flux of amino acids into the central nervous system. Beyond the endothelium, [SLC38A5](/details-gene/92745) is also a significant marker for specific, highly active immune cell populations. These include [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 7.33) and cells of the B cell lineage undergoing differentiation and antibody production, such as [plasmablast](/details-cell/CL0000980) (CSI: 6.48), [IgA plasma cell](/details-cell/CL0000987) (CSI: 2.96), and [IgG plasma cell](/details-cell/CL0000985) (CSI: 2.54). This suggests that [SLC38A5](/details-gene/92745) may be upregulated to meet the intense metabolic demands for amino acids required for protein synthesis in these cells. Additional significant expression is noted in various fibroblast populations, including [fibroblast of lung](/details-cell/CL0002553) (CSI: 4.60), and in secretory cells like [pancreatic acinar cell](/details-cell/CL0002064) (CSI: 3.98), further underscoring its role in cells with high metabolic and protein synthesis activity. ## Pathways and Molecular Function [SLC38A5](/details-gene/92745) functions as a transporter protein embedded in the [plasma membrane](/details-cell/GO:0005886). Its molecular activity is characterized as a [neutral amino acid, sodium:proton antiporter activity](/details-cell/GO:0140893), as defined by Gene Ontology. This mechanism allows it to mediate the transport of a range of neutral amino acids, supporting fundamental biological processes. The primary substrates for [SLC38A5](/details-gene/92745) include L-glutamine ([L-glutamine transmembrane transporter activity](/details-cell/GO:0015186)), L-asparagine ([L-asparagine transmembrane transporter activity](/details-cell/GO:0015182)), L-serine ([L-serine transmembrane transporter activity](/details-cell/GO:0015194)), glycine ([glycine transmembrane transporter activity](/details-cell/GO:0015187)), alanine ([alanine transmembrane transporter activity](/details-cell/GO:0022858)), and L-histidine ([L-histidine transmembrane transporter activity](/details-cell/GO:0005290)). This function was confirmed in early characterization studies of the protein, also known as SN2 ([Link](https://doi.org/10.1006/bbrc.2001.4504)). Consistent with its molecular function, [SLC38A5](/details-gene/92745) is a key component of several overarching biological pathways, as annotated by Reactome. These include [Amino acid transport across the plasma membrane](/details-gene/R-HSA-352230) and the broader category of [Slc-mediated transmembrane transport](/details-gene/R-HSA-425407). Its specific activity in brain endothelial cells directly contributes to the process of [transport across blood-brain barrier](/details-cell/GO:0150104), highlighting its physiological importance in neurobiology. ## Research Directions The specific expression pattern and function of [SLC38A5](/details-gene/92745) suggest several avenues for future investigation, particularly concerning its roles in neurodevelopment, immunology, and cancer biology. ### Proposed Hypotheses: 1. **Role in Neurodevelopment:** Given its high expression in [cerebral cortex endothelial cell](/details-cell/CL1001602) and the association of its deficiency with X-linked intellectual disability ([153245](https://omim.org/entry/300649)), [SLC38A5](/details-gene/92745) is hypothesized to be essential for regulating the availability of key amino acid precursors for neurotransmitter synthesis in the developing brain. Its dysfunction may disrupt neuronal homeostasis and lead to developmental defects. 2. **Function in Humoral Immunity:** The significant expression of [SLC38A5](/details-gene/92745) in [plasmablast](/details-cell/CL0000980) and plasma cells suggests it is critical for humoral immunity. It is hypothesized that [SLC38A5](/details-gene/92745) is upregulated during B cell terminal differentiation to supply the massive quantities of amino acids, such as glutamine and serine, required for the synthesis and secretion of antibodies. 3. **Involvement in Cancer Metabolism:** As a transporter for glutamine, a key metabolic fuel for many tumors, and based on reports linking it to cancer progression ([Link](https://doi.org/10.1073/pnas.0404089101)), [SLC38A5](/details-gene/92745) may function as a crucial mediator of metabolic reprogramming in cancer, facilitating nutrient uptake to sustain rapid proliferation. ### Suggested Experimental Approach: To test the hypothesis that [SLC38A5](/details-gene/92745) is essential for plasmablast function (Hypothesis 2), a conditional knockout mouse model with B-cell specific deletion of *Slc38a5* could be generated. B cells isolated from these mice and wild-type controls would be stimulated *in vitro* to differentiate into plasmablasts. The effects of *Slc38a5* loss could be assessed by measuring key functional outputs, including plasmablast differentiation efficiency via flow cytometry (CD138 expression), cell proliferation rates, and the quantity of secreted immunoglobulin using ELISA. Furthermore, metabolic flux analysis with 13C-labeled glutamine could directly determine the contribution of [SLC38A5](/details-gene/92745) to amino acid uptake and its subsequent incorporation into proteins. ### Therapeutic Potential: The role of [SLC38A5](/details-gene/92745) in supplying key nutrients for cellular growth makes it a plausible therapeutic target, particularly in oncology. Its function in glutamine transport suggests that its **inhibition** could serve as a strategy to starve glutamine-addicted tumors, a concept supported by studies implicating the gene in cancer development ([Link](https://doi.org/10.1073/pnas.0404089101)). As a plasma membrane protein, it is accessible to small molecule inhibitors or antibody-based therapies. However, its crucial role at the blood-brain barrier would necessitate careful consideration of potential neurological side effects when designing systemic inhibitors.

Genular Protein ID: 3137615804

Symbol: S38A5_HUMAN

Name: Solute carrier family 38 member 5

UniProtKB Accession Codes:

Q8WUX1 B3KT20 B5MDE6 B7WPJ9 Q6PIW9 Q8WYU2 Q96PQ4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 21 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 3 ExpressionAtlas 1 GO 24 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 21 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11243884

Title: Structure, function, and tissue expression pattern of human SN2, a subtype of the amino acid transport system N.

PubMed ID: 11243884

DOI: 10.1006/bbrc.2001.4504

PubMed ID: 15498874

Title: Large-scale cDNA transfection screening for genes related to cancer development and progression.

PubMed ID: 15498874

DOI: 10.1073/pnas.0404089101

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

Sequence Information:

  • Length: 472
  • Mass: 51457
  • Checksum: 2DDB4C03E5E78734
  • Sequence:
    • MELQDPKMNG ALPSDAVGYR QEREGFLPSR GPAPGSKPVQ FMDFEGKTSF GMSVFNLSNA 
IMGSGILGLA YAMAHTGVIF FLALLLCIAL LSSYSIHLLL TCAGIAGIRA YEQLGQRAFG 
PAGKVVVATV ICLHNVGAMS SYLFIIKSEL PLVIGTFLYM DPEGDWFLKG NLLIIIVSVL 
IILPLALMKH LGYLGYTSGL SLTCMLFFLV SVIYKKFQLG CAIGHNETAM ESEALVGLPS 
QGLNSSCEAQ MFTVDSQMSY TVPIMAFAFV CHPEVLPIYT ELCRPSKRRM QAVANVSIGA 
MFCMYGLTAT FGYLTFYSSV KAEMLHMYSQ KDPLILCVRL AVLLAVTLTV PVVLFPIRRA 
LQQLLFPGKA FSWPRHVAIA LILLVLVNVL VICVPTIRDI FGVIGSTSAP SLIFILPSIF 
YLRIVPSEVE PFLSWPKIQA LCFGVLGVLF MAVSLGFMFA NWATGQSRMS GH