Details for: SLC51A

Gene ID: 200931

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: SLC51A

Ensembl ID: ENSG00000163959

Description: solute carrier family 51 member A

Cell Significance Landscape

Associated with

Significant Cells

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

  • midzonal region hepatocyte CL0019028
    CSI 4.65
    rCSI 10.91%
    PRS 96.04
  • colon epithelial cell CL0011108
    CSI 4.64
    rCSI 4.86%
    PRS 97.33
  • stem cell CL0000034
    CSI 3.54
    rCSI 3.42%
    PRS 97.28
  • secretory cell CL0000151
    CSI 3.45
    rCSI 3.6%
    PRS 97.75
  • nasal mucosa goblet cell CL0002480
    CSI 3.27
    rCSI 3.79%
    PRS 97.35
  • Kupffer cell CL0000091
    CSI 3.24
    rCSI 7.42%
    PRS 98.35
  • periportal region hepatocyte CL0019026
    CSI 3.24
    rCSI 12.58%
    PRS 95.7
  • hepatic stellate cell CL0000632
    CSI 3.01
    rCSI 11.28%
    PRS 96.91
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.93
    rCSI 3.64%
    PRS 92.76
  • M cell of gut CL0000682
    CSI 2.74
    rCSI 2.92%
    PRS 98.28
  • intestinal epithelial cell CL0002563
    CSI 2.63
    rCSI 2.74%
    PRS 96.99
  • hepatocyte CL0000182
    CSI 2.57
    rCSI 4.61%
    PRS 96.69
  • lung ciliated cell CL1000271
    CSI 2.48
    rCSI 2.87%
    PRS 95.82
  • colonocyte CL1000347
    CSI 2.47
    rCSI 3.54%
    PRS 97.23
  • enterocyte CL0000584
    CSI 2.26
    rCSI 3.65%
    PRS 96.31
  • centrilobular region hepatocyte CL0019029
    CSI 2.11
    rCSI 5.51%
    PRS 95.45
  • club cell CL0000158
    CSI 1.98
    rCSI 2.9%
    PRS 96.98
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.93
    rCSI 12.04%
    PRS 95.11
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.27
    rCSI 3.56%
    PRS 98.55

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.

Comma-separated if multiple.
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)

Loading network (please wait)...

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 Analyzed for its specificity (CSI Z-SCORE), the data suggests that **[SLC51A](/details-gene/200931)**, which encodes the Solute Carrier Family 51 Subunit Alpha (OST-alpha), is not a specific marker for any single cell type. Instead, it appears to be a functionally important gene expressed across a range of epithelial and hepatic cells. It is a critical component of the Organic Solute Transporter alpha-beta heterodimer, which functions as the primary basolateral efflux system for bile acids, steroids, and other organic solutes in the intestine, liver, and kidney. Its essential role is underscored by findings that its deficiency leads to severe cholestatic liver disease (PubMed: [31863603](https://pubmed.ncbi.nlm.nih.gov/31863603)). ## Cellular Roles and Expression Landscape The expression profile of [SLC51A](/details-gene/200931), when evaluated for cellular specificity, reveals a consistent pattern of non-specific but functionally relevant expression. Within the **Overall** context, the CSI (Z-SCORE) is consistently 0.00 with non-significant p-values (p > 0.6) across all top-expressing cell populations. This indicates that while the gene is actively transcribed in these cells, its expression is not a unique or distinguishing feature that sets them apart from other related cell types. Despite the lack of specificity, the high Percentile Rank Scores (PRS > 95%) in cell types like [periportal region hepatocytes](/details-cell/CL0019026) (PRS: 95.70%) and [colon epithelial cells](/details-cell/CL0011108) (PRS: 97.33%) suggest that [SLC51A](/details-gene/200931) is among the more highly expressed genes in these lineages. Its presence in a variety of absorptive and secretory cells—including [hepatocytes](/details-cell/CL0000182), [enterocytes](/details-cell/CL0000584), [Kupffer cells](/details-cell/CL0000091), and [colonocytes](/details-cell/CL1000347)—is consistent with its established role in the enterohepatic circulation of bile acids and steroids. Research has confirmed that the OSTalpha-OSTbeta complex, of which SLC51A is a part, serves as a major basolateral transporter in human intestinal, renal, and biliary epithelia (PubMed: [16317684](https://pubmed.ncbi.nlm.nih.gov/16317684)). The expression is regulated by the farnesoid X receptor (FXR), a nuclear receptor that senses bile acid levels, thereby linking its transcription directly to physiological demand (PubMed: [16269519](https://pubmed.ncbi.nlm.nih.gov/16269519), [16251721](https://pubmed.ncbi.nlm.nih.gov/16251721)). ## Pathways and Molecular Function The functional annotations for [SLC51A](/details-gene/200931) strongly align with its observed cellular expression pattern. It is centrally involved in '[Bile acid and bile salt transport](/details-go/GO:0015721)' and localizes to the '[Basolateral plasma membrane](/details-go/GO:0016323)', which is the correct subcellular compartment for a protein that exports solutes from epithelial cells into circulation. This function is a key step in the Reactome pathway for '[Recycling of bile acids and salts](/details-reactome/R-HSA-159418)'. Molecularly, SLC51A is inactive on its own and requires heterodimerization with SLC51B (OST-beta) to form a functional transport unit, a fact supported by the GO annotation '[Protein heterodimerization activity](/details-go/GO:0046982)' and confirmed by foundational research (PubMed: [12719432](https://pubmed.ncbi.nlm.nih.gov/12719432)). This complex facilitates the transport of a wide range of substrates, including major conjugated bile acids, dehydroepiandrosterone sulfate (DHEAS), estrone-3-sulfate, and digoxin, highlighting its importance in both nutrient recycling and xenobiotic detoxification. ## Research Directions The broad but non-specific expression pattern of [SLC51A](/details-gene/200931) suggests its role is more of a constitutive housekeeping function in specialized tissues rather than a dynamic cell identity marker. Future research could explore the regulatory dynamics that control its activity and potential context-dependent roles. ### Testable Hypotheses: 1. **Hypothesis: Post-translational regulation dictates SLC51A activity.** The low specificity score (CSI Z-SCORE) suggests that transcriptional levels of [SLC51A](/details-gene/200931) may be relatively stable in healthy tissues. We hypothesize that the transporter's activity is primarily regulated post-translationally, such as through dynamic changes in its localization to the basolateral membrane or altered stability of the OSTalpha-OSTbeta complex in response to high bile acid flux. * **Experimental Approach:** Utilize polarized intestinal epithelial cell models (e.g., Caco-2) and treat them with varying concentrations of bile acids. Perform cell surface biotinylation followed by Western blotting to quantify the amount of SLC51A at the basolateral membrane. Co-immunoprecipitation could be used to assess the stability of the heterodimer with SLC51B under these conditions. 2. **Hypothesis: SLC51A expression becomes a specific marker of cellular stress in cholestatic disease.** In pathological states such as cholestasis, where bile acid homeostasis is severely disrupted, we hypothesize that [SLC51A](/details-gene/200931) expression becomes upregulated and highly specific in hepatocytes or cholangiocytes as a compensatory defense mechanism to efflux toxic bile acids. * **Experimental Approach:** Perform single-cell RNA sequencing on liver biopsies from patients with primary biliary cholangitis (PBC) and healthy controls. A comparative differential specificity analysis (re-calculating CSI Z-Scores for disease vs. healthy) would reveal if [SLC51A](/details-gene/200931) emerges as a specific marker for stressed hepatocytes or other cell types in the diseased liver microenvironment. 3. **Hypothesis: SLC51A transports neurosteroids in the central nervous system.** The observed expression in [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) is intriguing and suggests a function beyond bile acid transport. We hypothesize that in the brain, [SLC51A](/details-gene/200931) is involved in the transport of sulfated neurosteroids, which are known to modulate GABAergic signaling, thereby contributing to the regulation of cortical network activity. * **Experimental Approach:** Generate a conditional knockout mouse model where *Slc51a* is specifically deleted in parvalbumin-positive interneurons. Use in vitro brain slice electrophysiology to record synaptic currents from these neurons and assess for changes in GABAergic transmission. Mass spectrometry on brain tissue could be used to detect altered levels of specific neurosteroids in the knockout model. ### Therapeutic Potential Given that loss-of-function mutations in [SLC51A](/details-gene/200931) cause a severe Mendelian disorder of cholestasis and liver fibrosis known as Organic Solute Transporter Alpha Deficiency ([OMIM: 618774](https://omim.org/entry/618774)), the gene represents a potential therapeutic target. Gene replacement therapy could be a viable strategy for treating this inherited deficiency. Furthermore, small molecule modulators that enhance the activity or expression of the OSTalpha-OSTbeta complex might offer therapeutic benefits in acquired cholestatic conditions where bile acid efflux is impaired. However, its broad expression in the liver, intestine, and kidney necessitates the development of tissue-specific therapeutic strategies to avoid off-target effects.

Genular Protein ID: 3164062777

Symbol: OSTA_HUMAN

Name: Solute carrier family 51 subunit alpha

UniProtKB Accession Codes:

Q86UW1 Q6ZMC7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 11 ChEMBL 1 DNASU 1 DisGeNET 1 DrugBank 4 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 10 GeneCards 1 GeneTree 1 GeneWiki 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 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 11 SMART 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12719432

Title: Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta.

PubMed ID: 12719432

DOI: 10.1074/jbc.m301106200

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16317684

Title: OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia.

PubMed ID: 16317684

DOI: 10.1002/hep.20961

PubMed ID: 16269519

Title: The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-alpha and -beta genes.

PubMed ID: 16269519

DOI: 10.1152/ajpgi.00430.2005

PubMed ID: 16251721

Title: FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine.

PubMed ID: 16251721

DOI: 10.1194/jlr.m500417-jlr200

PubMed ID: 31863603

Title: Organic solute transporter alpha deficiency: A disorder with cholestasis, liver fibrosis, and congenital diarrhea.

PubMed ID: 31863603

DOI: 10.1002/hep.31087

Sequence Information:

  • Length: 340
  • Mass: 37735
  • Checksum: D6725C479A7DF114
  • Sequence:
    • MEPGRTQIKL DPRYTADLLE VLKTNYGIPS ACFSQPPTAA QLLRALGPVE LALTSILTLL 
ALGSIAIFLE DAVYLYKNTL CPIKRRTLLW KSSAPTVVSV LCCFGLWIPR SLVLVEMTIT 
SFYAVCFYLL MLVMVEGFGG KEAVLRTLRD TPMMVHTGPC CCCCPCCPRL LLTRKKLQLL 
MLGPFQYAFL KITLTLVGLF LVPDGIYDPA DISEGSTALW INTFLGVSTL LALWTLGIIS 
RQARLHLGEQ NMGAKFALFQ VLLILTALQP SIFSVLANGG QIACSPPYSS KTRSQVMNCH 
LLILETFLMT VLTRMYYRRK DHKVGYETFS SPDLDLNLKA