Details for: SLC49A3

Gene ID: 84179

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: SLC49A3

Ensembl ID: ENSG00000169026

Description: solute carrier family 49 member 3

Cell Significance Landscape

Associated with

Significant Cells

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

  • lung macrophage CL1001603
    CSI 1.39
    rCSI 3.1%
    PRS 99.83

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [SLC49A3](/details-gene/84179) is a protein-coding gene located on chromosome 4p16.3, which encodes a member of the solute carrier family of transporters. The resulting protein, also known as Major facilitator superfamily domain-containing protein 7, is an integral membrane protein predicted to function in transmembrane transport. Foundational cDNA sequencing projects have established its existence and sequence [[Link](https://doi.org/10.1101/gr.1293003), [Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504)]. **Overall** expression analysis indicates that [SLC49A3](/details-gene/84179) shows significant expression in [lung macrophage](/details-cell/CL1001603), suggesting a specialized role in the metabolic or homeostatic functions of these tissue-resident immune cells. ## Cellular Roles and Expression Landscape The expression profile of [SLC49A3](/details-gene/84179) points to a potentially specialized function within the immune system, particularly in tissue-resident phagocytes. **Overall**, the most significant expression signal for [SLC49A3](/details-gene/84179) is observed in [lung macrophage](/details-cell/CL1001603) (CSI: 1.39). This finding suggests that the gene's primary role may be linked to the unique physiological demands and microenvironment of the lung, where these macrophages are critical for clearing debris, pathogens, and maintaining tissue homeostasis. The data does not provide information on cell types where [SLC49A3](/details-gene/84179) is not expressed, limiting a full assessment of its tissue specificity. Furthermore, without cross-contextual data, it is unclear if this expression is static or dynamically regulated during health and disease. ## Pathways and Molecular Function Functional annotation data aligns with the role of [SLC49A3](/details-gene/84179) as a transporter protein. It is associated with the Gene Ontology (GO) terms 'Transmembrane transporter activity' ([GO:0022857](https://www.ebi.ac.uk/QuickGO/term/GO:0022857)) and the broader biological process of 'Transmembrane transport' ([GO:0055085](https://www.ebi.ac.uk/QuickGO/term/GO:0055085)). As a predicted integral component of the 'Membrane' ([GO:0016020](https://www.ebi.ac.uk/QuickGO/term/GO:0016020)), its function is likely to involve the movement of specific, yet currently unidentified, substrates across the cell membrane. This transporter activity is consistent with its high significance in [lung macrophage](/details-cell/CL1001603), a cell type with high metabolic and phagocytic demands. The transport of nutrients, ions, or metabolites by [SLC49A3](/details-gene/84179) may be essential for cellular energy, signaling, or the execution of effector functions in the lung environment. The annotation of 'Protein binding' ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)) suggests that its activity could be regulated through interaction with other proteins, potentially as part of a larger transport complex. ## Research Directions The specific role of [SLC49A3](/details-gene/84179), particularly its substrate specificity and physiological importance in [lung macrophage](/details-cell/CL1001603), remains to be elucidated. Its high significance in this cell type presents several avenues for future investigation. ### Proposed Hypotheses: 1. **Metabolic Support for Macrophage Function:** [SLC49A3](/details-gene/84179) transports a specific substrate (e.g., an amino acid, polyamine, or metabolite) that is critical for maintaining the metabolic fitness, phagocytic capacity, or inflammatory response of [lung macrophage](/details-cell/CL1001603) upon encountering pathogens or environmental particulates. 2. **Regulation in Pulmonary Disease:** The expression or activity of [SLC49A3](/details-gene/84179) in [lung macrophage](/details-cell/CL1001603) is dynamically altered during inflammatory lung conditions, such as asthma, chronic obstructive pulmonary disease (COPD), or acute respiratory distress syndrome (ARDS), contributing to macrophage polarization and disease pathogenesis. ### Experimental Approach: To test the first hypothesis, the function and substrate of [SLC49A3](/details-gene/84179) in macrophages could be investigated. A robust approach would involve generating a stable [SLC49A3](/details-gene/84179) knockout in a human macrophage-like cell line (e.g., THP-1) using CRISPR-Cas9. A comparative, untargeted metabolomics analysis of intracellular and extracellular media from wild-type versus knockout cells could identify substrates that are either depleted or accumulated, thereby revealing the transporter's cargo. Subsequently, these knockout macrophages could be assessed for functional defects in key processes like phagocytosis, efferocytosis, and cytokine production in response to inflammatory stimuli (e.g., LPS or viral mimics). ### Therapeutic Potential: Given its transporter function and notable expression in [lung macrophage](/details-cell/CL1001603), [SLC49A3](/details-gene/84179) may represent a novel therapeutic target for modulating lung inflammation. If its substrate is found to fuel pro-inflammatory macrophage activity, targeted inhibition via small molecules could offer a strategy to dampen excessive inflammation in diseases like ARDS. Conversely, if it supports resolving or tissue-reparative macrophage functions, developing agonists could be a potential therapeutic avenue for promoting recovery from lung injury. The apparent cellular specificity would be advantageous, potentially minimizing systemic off-target effects.

Genular Protein ID: 2739320442

Symbol: S49A3_HUMAN

Name: Major facilitator superfamily domain-containing protein 7

UniProtKB Accession Codes:

Q6UXD7 A8K7J5 Q6XYD4 Q8N6H1 Q9H6H6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 3 ExpressionAtlas 1 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 15498874

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

PubMed ID: 15498874

DOI: 10.1073/pnas.0404089101

Sequence Information:

  • Length: 560
  • Mass: 58427
  • Checksum: 41848AAEB46601A4
  • Sequence:
    • MAGPTEAETG LAEPRALCAQ RGHRTYARRW VFLLAISLLN CSNATLWLSF APVADVIAED 
LVLSMEQINW LSLVYLVVST PFGVAAIWIL DSVGLRAATI LGAWLNFAGS VLRMVPCMVV 
GTQNPFAFLM GGQSLCALAQ SLVIFSPAKL AALWFPEHQR ATANMLATMS NPLGVLVANV 
LSPVLVKKGE DIPLMLGVYT IPAGVVCLLS TICLWESVPP TPPSAGAASS TSEKFLDGLK 
LQLMWNKAYV ILAVCLGGMI GISASFSALL EQILCASGHS SGFSGLCGAL FITFGILGAL 
ALGPYVDRTK HFTEATKIGL CLFSLACVPF ALVSQLQGQT LALAATCSLL GLFGFSVGPV 
AMELAVECSF PVGEGAATGM IFVLGQAEGI LIMLAMTALT VRRSEPSLST CQQGEDPLDW 
TVSLLLMAGL CTFFSCILAV FFHTPYRRLQ AESGEPPSTR NAVGGADSGP GVDRGGAGRA 
GVLGPSTATP ECTARGASLE DPRGPGSPHP ACHRATPRAQ GPAATDAPSR PGRLAGRVQA 
SRFIDPAGSH SSFSSPWVIT