Details for: SLC10A3

Gene ID: 8273

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: SLC10A3

Ensembl ID: ENSG00000126903

Description: solute carrier family 10 member 3

Cell Significance Landscape

Associated with

Significant Cells

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

  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 9.44
    rCSI 6.29%
    PRS 97.84
  • fibroblast of lung CL0002553
    CSI 6.77
    rCSI 6.3%
    PRS 96.62
  • megakaryocyte CL0000556
    CSI 3.98
    rCSI 17.25%
    PRS 95.26
  • extravillous trophoblast CL0008036
    CSI 3.76
    rCSI 4.65%
    PRS 94.22
  • CD4-positive helper T cell CL0000492
    CSI 3.19
    rCSI 2.42%
    PRS 99.23
  • myeloid leukocyte CL0000766
    CSI 3.19
    rCSI 2.94%
    PRS 96.61
  • goblet cell CL0000160
    CSI 3.12
    rCSI 2.95%
    PRS 93.88
  • epithelial cell of lung CL0000082
    CSI 2.91
    rCSI 2.41%
    PRS 96.44
  • group 3 innate lymphoid cell CL0001071
    CSI 2.62
    rCSI 1.97%
    PRS 97.11
  • activated type II NK T cell CL0000931
    CSI 2.59
    rCSI 2.92%
    PRS 98.55
  • bronchus fibroblast of lung CL2000093
    CSI 2.47
    rCSI 2%
    PRS 95.51
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 2.46
    rCSI 4.21%
    PRS 98.15
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.19
    rCSI 2.23%
    PRS 97.93
  • erythrocyte CL0000232
    CSI 2.14
    rCSI 4.86%
    PRS 93.76
  • granulocyte CL0000094
    CSI 2.13
    rCSI 3.25%
    PRS 97.6
  • placental villous trophoblast CL2000060
    CSI 2.05
    rCSI 3.16%
    PRS 94.13
  • club cell CL0000158
    CSI 1.79
    rCSI 2.62%
    PRS 92.98
  • syncytiotrophoblast cell CL0000525
    CSI 1.39
    rCSI 3.99%
    PRS 95.19
  • platelet CL0000233
    CSI 1.15
    rCSI 4.79%
    PRS 91.9
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.52
    rCSI 2.63%
    PRS 98.68

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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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 [SLC10A3](/details-gene/8273), or Solute Carrier Family 10 Member 3, is a protein-coding gene located on the X chromosome at position Xq28 ([Link](https://doi.org/10.1038/nature03440)). As a member of the SLC10 solute carrier family, it is functionally annotated as an integral [membrane](/details-go/GO:0016020) protein with [bile acid:sodium symporter activity](/details-go/GO:0008508). While its molecular function points towards a role in [bile acid and bile salt transport](/details-go/GO:0015721), its expression landscape is notably diverse. **Overall**, [SLC10A3](/details-gene/8273) shows the highest significance in immune cells, particularly [CD16-positive, CD56-dim natural killer cells](/details-cell/CL0000939), as well as in stromal cells such as [fibroblasts of the lung](/details-cell/CL0002553). This broad expression pattern suggests that its biological role may extend beyond canonical hepatic and intestinal bile acid metabolism, potentially encompassing functions in immune regulation and tissue homeostasis. The gene has a clinical association with OMIM entry [312090](https://omim.org/entry/312090). ## Cellular Roles and Expression Landscape The expression profile of [SLC10A3](/details-gene/8273) indicates a widespread but functionally intriguing distribution across multiple cell lineages, with a pronounced significance in the immune system. - **Immune System Dominance:** The gene's most significant expression is observed in [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939) (CSI: 9.44), a major cytotoxic lymphocyte population. High significance is also noted across a spectrum of adaptive and innate immune cells, including [CD4-positive helper T cells](/details-cell/CL0000492), [myeloid leukocytes](/details-cell/CL0000766), [group 3 innate lymphoid cells](/details-cell/CL0001071), [activated type II NK T cells](/details-cell/CL0000931), [activated CD8-positive, alpha-beta T cells](/details-cell/CL0001049), and their precursors like [double-positive, alpha-beta thymocytes](/details-cell/CL0000809). This consistent pattern suggests a fundamental role for [SLC10A3](/details-gene/8273) in lymphocyte biology. - **Stromal and Epithelial Significance:** Beyond the immune system, [SLC10A3](/details-gene/8273) is highly significant in [fibroblasts of the lung](/details-cell/CL0002553) (CSI: 6.77), indicating a potential role in lung tissue structure or response to injury. Its presence in specialized secretory and barrier cells like [goblet cells](/details-cell/CL0000160) and [epithelial cells of the lung](/details-cell/CL0000082) further supports a function in mucosal tissues. - **Hematopoietic and Placental Roles:** The gene also shows significance in hematopoietic cells, including [megakaryocytes](/details-cell/CL0000556) and [erythrocytes](/details-cell/CL0000232), and in specialized placental cells such as [extravillous trophoblasts](/details-cell/CL0008036). This suggests its function is not confined to terminally differentiated cells and may be important during development and hematopoiesis. **Overall**, the diverse expression profile of [SLC10A3](/details-gene/8273) points to a pleiotropic function where its transport activity may be co-opted by various cell types for distinct biological purposes, from immune surveillance to tissue maintenance. ## Pathways and Molecular Function The functional annotations for [SLC10A3](/details-gene/8273) center on its identity as a transmembrane transporter. According to Gene Ontology, it participates in [transmembrane transport](/details-go/GO:0055085) and, more specifically, [bile acid and bile salt transport](/details-go/GO:0015721). Its molecular function is defined as [bile acid:sodium symporter activity](/details-go/GO:0008508), indicating it cotransports sodium ions and bile acids across the cell [membrane](/details-go/GO:0016020). While bile acids are primarily known for their role in digestion, they are now recognized as important signaling molecules that can modulate inflammation and immune cell function through receptors like FXR and TGR5. The high significance of [SLC10A3](/details-gene/8273) in various lymphocytes, particularly [NK cells](/details-cell/CL0000939), suggests that it may mediate the uptake of bile acids into these cells, thereby influencing their activation, differentiation, or effector functions. Furthermore, its annotated involvement in the [response to retinoic acid](/details-go/GO:0032526) is consistent with a role in regulating the differentiation and function of immune and epithelial cells, where retinoid signaling is a critical pathway. ## Research Directions The widespread expression of a bile acid transporter outside of the enterohepatic system presents several intriguing avenues for research. The data suggest that [SLC10A3](/details-gene/8273) may have non-canonical roles in immunity and tissue physiology. **Proposed Hypotheses:** 1. [SLC10A3](/details-gene/8273) modulates the effector functions of [CD16-positive, CD56-dim NK cells](/details-cell/CL0000939) by transporting specific bile acids that act as intracellular signaling molecules to regulate cytotoxicity and cytokine production. 2. In [lung fibroblasts](/details-cell/CL0002553), [SLC10A3](/details-gene/8273)-mediated transport is involved in the cellular response to inflammation or tissue damage, potentially by importing signaling lipids that influence pro-fibrotic or anti-fibrotic gene expression programs. 3. The expression of [SLC10A3](/details-gene/8273) in [extravillous trophoblasts](/details-cell/CL0008036) is critical for mediating maternal-fetal immune tolerance by regulating local concentrations of immunomodulatory bile acids at the placental interface. **Suggested Experimental Approach:** To test the first hypothesis regarding the role of [SLC10A3](/details-gene/8273) in NK cell function, a series of *in vitro* experiments could be conducted. Primary human [CD16-positive, CD56-dim NK cells](/details-cell/CL0000939) would be isolated and subjected to CRISPR-Cas9-mediated knockout of [SLC10A3](/details-gene/8273). The functional consequences would be assessed by co-culturing control and knockout NK cells with target cancer cells (e.g., K562) and measuring target cell lysis via flow cytometry. To determine if this function is bile acid-dependent, these assays would be performed in the presence or absence of specific bile acids (e.g., deoxycholic acid). Changes in NK cell activation markers (e.g., CD69, CD107a) and cytokine secretion (e.g., IFN-γ, TNF-α) would be quantified to further dissect the mechanism. **Therapeutic Potential:** As a multi-pass transmembrane protein, [SLC10A3](/details-gene/8273) is a potentially druggable target for small molecule modulators. Its therapeutic potential depends heavily on its specific role in disease. If [SLC10A3](/details-gene/8273) activity enhances the anti-tumor function of NK cells, developing small molecule **activators** could be a novel strategy for immuno-oncology. Conversely, if its activity in fibroblasts promotes fibrosis, **inhibition** could be explored as an anti-fibrotic therapy. However, its broad expression across multiple critical cell types poses a significant risk for off-target effects, necessitating the development of highly specific inhibitors or cell-targeted delivery systems.

Genular Protein ID: 2596510499

Symbol: P3_HUMAN

Name: P3 protein

UniProtKB Accession Codes:

P09131 Q5HY79 Q9BSL2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 4 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 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 NCBIfam 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 RNAct 1 RefSeq 4 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 3186440

Title: CpG islands of the X chromosome are gene associated.

PubMed ID: 3186440

DOI: 10.1093/nar/16.20.9527

PubMed ID: 8733135

Title: Long-range sequence analysis in Xq28: thirteen known and six candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and G6PD loci.

PubMed ID: 8733135

DOI: 10.1093/hmg/5.5.659

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

Sequence Information:

  • Length: 477
  • Mass: 50333
  • Checksum: 49CB363EB3B66A1D
  • Sequence:
    • MVLMQDKGSS QQWPGLGGEG GGTGPLSMLR AALLLISLPW GAQGTASTSL STAGGHTVPP 
TGGRYLSIGD GSVMEFEFPE DSEGIIVISS QYPGQANRTA PGPMLRVTSL DTEVLTIKNV 
SAITWGGGGG FVVSIHSGLA GLAPLHIQLV DAHEAPPTLI EERRDFCIKV SPAEDTPATL 
SADLAHFSEN PILYLLLPLI FVNKCSFGCK VELEVLKGLM QSPQPMLLGL LGQFLVMPLY 
AFLMAKVFML PKALALGLII TCSSPGGGGS YLFSLLLGGD VTLAISMTFL STVAATGFLP 
LSSAIYSRLL SIHETLHVPI SKILGTLLFI AIPIAVGVLI KSKLPKFSQL LLQVVKPFSF 
VLLLGGLFLA YRMGVFILAG IRLPIVLVGI TVPLVGLLVG YCLATCLKLP VAQRRTVSIE 
VGVQNSLLAL AMLQLSLRRL QADYASQAPF IVALSGTSEM LALVIGHFIY SSLFPVP

Genular Protein ID: 651296260

Symbol: A0A0A0MS43_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0A0MS43

Database IDs:

ARBA 3 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 1 GeneTree 1 HGNC 1 InterPro 3 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 1 PhylomeDB 1 Proteomes 2 ProteomicsDB 1 RefSeq 2 SAM 2 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

Sequence Information:

  • Length: 532
  • Mass: 55900
  • Checksum: CCDF4C23245C8931
  • Sequence:
    • MAGPRPPGDS PAIKEDSTGL GPTHEPFSGQ PNSTSGDVLL SRRGPGHAIR PPGRAMVLMQ 
DKGSSQQWPG LGGEGGGTGP LSMLRAALLL ISLPWGAQGT ASTSLSTAGG HTVPPTGGRY 
LSIGDGSVME FEFPEDSEGI IVISSQYPGQ ANRTAPGPML RVTSLDTEVL TIKNVSAITW 
GGGGGFVVSI HSGLAGLAPL HIQLVDAHEA PPTLIEERRD FCIKVSPAED TPATLSADLA 
HFSENPILYL LLPLIFVNKC SFGCKVELEV LKGLMQSPQP MLLGLLGQFL VMPLYAFLMA 
KVFMLPKALA LGLIITCSSP GGGGSYLFSL LLGGDVTLAI SMTFLSTVAA TGFLPLSSAI 
YSRLLSIHET LHVPISKILG TLLFIAIPIA VGVLIKSKLP KFSQLLLQVV KPFSFVLLLG 
GLFLAYRMGV FILAGIRLPI VLVGITVPLV GLLVGYCLAT CLKLPVAQRR TVSIEVGVQN 
SLLALAMLQL SLRRLQADYA SQAPFIVALS GTSEMLALVI GHFIYSSLFP VP