Details for: SLCO4A1

Gene ID: 28231

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: SLCO4A1

Ensembl ID: ENSG00000101187

Description: solute carrier organic anion transporter family member 4A1

Cell Significance Landscape

Associated with

Significant Cells

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

  • extravillous trophoblast CL0008036
    CSI 19.11
    rCSI 23.64%
    PRS 96.44
  • intestinal tuft cell CL0019032
    CSI 11.29
    rCSI 17.25%
    PRS 97.16
  • stem cell CL0000034
    CSI 8.79
    rCSI 8.48%
    PRS 96.24
  • pulmonary capillary endothelial cell CL4028001
    CSI 4.24
    rCSI 8.08%
    PRS 98.8
  • cerebral cortex endothelial cell CL1001602
    CSI 3.98
    rCSI 6.89%
    PRS 95.41
  • melanocyte CL0000148
    CSI 3.92
    rCSI 2.9%
    PRS 96
  • capillary endothelial cell CL0002144
    CSI 3.84
    rCSI 7.04%
    PRS 95.7
  • Kupffer cell CL0000091
    CSI 3.05
    rCSI 6.98%
    PRS 97.87
  • keratinocyte CL0000312
    CSI 2.97
    rCSI 2.49%
    PRS 96.67
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.83
    rCSI 4.52%
    PRS 98.24
  • blood vessel endothelial cell CL0000071
    CSI 2.73
    rCSI 5.66%
    PRS 96.65
  • intestine goblet cell CL0019031
    CSI 2.62
    rCSI 2.32%
    PRS 96.3
  • ependymal cell CL0000065
    CSI 2.48
    rCSI 5.03%
    PRS 87.99
  • pulmonary artery endothelial cell CL1001568
    CSI 2.41
    rCSI 3.28%
    PRS 98.5
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.28
    rCSI 7.02%
    PRS 97.85
  • renal principal cell CL0005009
    CSI 2.26
    rCSI 5.86%
    PRS 97.03
  • colon epithelial cell CL0011108
    CSI 2.22
    rCSI 2.33%
    PRS 96.51
  • epithelial cell of proximal tubule CL0002306
    CSI 2.21
    rCSI 5.4%
    PRS 93.88
  • retinal rod cell CL0000604
    CSI 2.12
    rCSI 3.73%
    PRS 94.96
  • squamous epithelial cell CL0000076
    CSI 1.95
    rCSI 4.64%
    PRS 94.29
  • cardiac endothelial cell CL0010008
    CSI 1.9
    rCSI 7.67%
    PRS 97.65
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.83
    rCSI 4.73%
    PRS 96.51
  • tuft cell of colon CL0009041
    CSI 1.78
    rCSI 4.15%
    PRS 97.13
  • lung macrophage CL1001603
    CSI 1.55
    rCSI 3.47%
    PRS 99.11
  • melanocyte of skin CL1000458
    CSI 1.47
    rCSI 2%
    PRS 79.08
  • basal cell of epidermis CL0002187
    CSI 1.31
    rCSI 2.32%
    PRS 78.07
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.3
    rCSI 3.5%
    PRS 97.96
  • endothelial cell of vascular tree CL0002139
    CSI 1.26
    rCSI 6.91%
    PRS 95.12
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.77
    rCSI 5.27%
    PRS 98.36
  • vasa recta descending limb cell CL1001285
    CSI 0.68
    rCSI 5.44%
    PRS 98.52
  • cytotoxic T cell CL0000910
    CSI 0.39
    rCSI 2.25%
    PRS 94.58

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)

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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 [SLCO4A1](/details-gene/28231), or Solute Carrier Organic Anion Transporter Family Member 4A1, is a protein-coding gene located on chromosome 20q13.33. It functions as a transmembrane transporter responsible for the sodium-independent transport of organic anions, including prostaglandins and thyroid hormones. Expression data indicates that [SLCO4A1](/details-gene/28231) is a highly significant marker for specialized cell types at physiological barriers. **Overall**, it shows the most pronounced significance in [extravillous trophoblast](/details-cell/CL0008036) cells of the placenta and [intestinal tuft cell](/details-cell/CL0019032)s, suggesting a critical role in maternal-fetal exchange and intestinal homeostasis, respectively. Its widespread, albeit lower, significance in various endothelial cell populations further points to a role in regulating molecular transport across vascular beds throughout the body. ## Cellular Roles and Expression Landscape The expression profile of [SLCO4A1](/details-gene/28231) highlights its specialized function in tissues that form critical interfaces between different physiological compartments. The most significant expression is observed in the [extravillous trophoblast](/details-cell/CL0008036) (CSI: 19.11), a key cell type in the placenta responsible for anchoring the fetus and mediating nutrient and hormone exchange. This is consistent with studies identifying its role in transporting steroid sulfates in the placenta ([Link](https://doi.org/10.1152/ajpendo.00257.2002)). A second major site of high significance is the gastrointestinal tract, specifically in [intestinal tuft cell](/details-cell/CL0019032)s (CSI: 11.29) and [intestine goblet cell](/details-cell/CL0019031)s (CSI: 2.62). Tuft cells are chemosensory cells that regulate mucosal immune responses, and the high expression of a prostaglandin transporter in these cells suggests a role for [SLCO4A1](/details-gene/28231) in modulating local inflammatory signaling. Furthermore, [SLCO4A1](/details-gene/28231) demonstrates notable significance across a diverse range of endothelial cells, including [pulmonary capillary endothelial cell](/details-cell/CL4028001)s (CSI: 4.24), [cerebral cortex endothelial cell](/details-cell/CL1001602)s (CSI: 3.98), and [capillary endothelial cell](/details-cell/CL0002144)s (CSI: 3.84). This pattern suggests a conserved role in mediating the transport of its substrates across the blood-tissue barriers in the lungs, brain, and other organs. Its expression in hepatic [Kupffer cell](/details-cell/CL0000091)s (CSI: 3.05) and [endothelial cell of pericentral hepatic sinusoid](/details-cell/CL0019022)s (CSI: 2.28) may also indicate involvement in liver clearance and metabolism. ## Pathways and Molecular Function The functions of [SLCO4A1](/details-gene/28231) are well-defined by its annotations as a solute carrier. Its involvement in 'Slc-mediated transmembrane transport' ([R-HSA-425407](https://reactome.org/content/detail/R-HSA-425407)) and the 'Transport of organic anions' ([R-HSA-879518](https://reactome.org/content/detail/R-HSA-879518)) underpins its broad physiological activity. **Molecular Function (GO):** The gene product primarily exhibits 'Organic anion transmembrane transporter activity' ([GO:0008514](https://www.ebi.ac.uk/QuickGO/term/GO:0008514)) and 'Sodium-independent organic anion transmembrane transporter activity' ([GO:0015347](https://www.ebi.ac.uk/QuickGO/term/GO:0015347)). Its specificity for key signaling molecules is highlighted by its annotated roles in 'Prostaglandin transmembrane transporter activity' ([GO:0015132](https://www.ebi.ac.uk/QuickGO/term/GO:0015132)) and 'Thyroid hormone transmembrane transporter activity' ([GO:0015349](https://www.ebi.ac.uk/QuickGO/term/GO:0015349)). This latter function is particularly relevant to its high expression in placental trophoblasts and cerebral endothelial cells, sites where thyroid hormone transport is crucial for fetal development and brain function, respectively ([Link](https://doi.org/10.1210/endo.142.5.8115)). **Biological Process (GO):** Consistent with its molecular functions, [SLCO4A1](/details-gene/28231) participates in 'Prostaglandin transport' ([GO:0015732](https://www.ebi.ac.uk/QuickGO/term/GO:0015732)) and 'Thyroid hormone transport' ([GO:0070327](https://www.ebi.ac.uk/QuickGO/term/GO:0070327)). These processes are critical for intercellular signaling, inflammation, and metabolic regulation. The transporter is localized to the 'Plasma membrane' ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)), specifically the 'Basolateral plasma membrane' ([GO:0016323](https://www.ebi.ac.uk/QuickGO/term/GO:0016323)) in polarized cells, which dictates the directional flow of substrates across cellular layers. ## Research Directions The specific expression pattern and established functions of [SLCO4A1](/details-gene/28231) suggest several avenues for future research into its role in health and disease. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [extravillous trophoblast](/details-cell/CL0008036)s and its role in transporting thyroid hormones, [SLCO4A1](/details-gene/28231) may be essential for proper neurodevelopment *in utero*. We hypothesize that genetic variants or environmental factors that reduce [SLCO4A1](/details-gene/28231) function at the placental barrier could impair maternal-fetal thyroid hormone transfer, potentially contributing to congenital hypothyroidism or neurodevelopmental disorders. 2. Based on its high expression in [intestinal tuft cell](/details-cell/CL0019032)s and its function as a prostaglandin transporter, we hypothesize that [SLCO4A1](/details-gene/28231) is a key regulator of type 2 mucosal immunity. It may mediate the uptake or release of prostaglandins that influence tuft cell activation and subsequent downstream signaling to immune cells, thereby shaping the response to helminth infections or allergic inflammation. **Key Experimental Approach:** To test the hypothesis regarding its role in placental function (Hypothesis 1), a multi-pronged approach could be employed. CRISPR-Cas9 could be used to knock out [SLCO4A1](/details-gene/28231) in human trophoblast stem cells, which can be differentiated into syncytiotrophoblasts and extravillous trophoblasts. The impact of the knockout on the cellular uptake and transepithelial transport of radiolabeled thyroid hormones (T3 and T4) and other known substrates could be quantified. Furthermore, proteomic and transcriptomic analysis of these knockout cells could reveal compensatory changes in other transporters and identify downstream signaling pathways affected by the loss of [SLCO4A1](/details-gene/28231) function. **Therapeutic Potential:** As a multi-specific transporter located at critical physiological barriers, [SLCO4A1](/details-gene/28231) presents a complex but potentially valuable therapeutic target. Its expression on cerebral endothelial cells suggests it could be exploited for drug delivery to the central nervous system, assuming brain-penetrant drugs could be designed as substrates. Conversely, in pathological contexts such as inflammatory bowel disease, selective inhibition of [SLCO4A1](/details-gene/28231) in intestinal epithelial cells might offer a novel anti-inflammatory strategy by modulating local prostaglandin levels. However, its broad expression profile, including in the liver and placenta, suggests that systemic targeting would likely carry a high risk of off-target effects, necessitating the development of highly tissue-specific inhibitors or delivery mechanisms.

Genular Protein ID: 3717434208

Symbol: SO4A1_HUMAN

Name: Solute carrier organic anion transporter family member 4A1

UniProtKB Accession Codes:

Q96BD0 Q9H4T7 Q9H4T8 Q9H8P2 Q9NWX8 Q9UI35 Q9UIG7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 15 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 14 EMBL 8 Ensembl 2 ExpressionAtlas 1 GO 8 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 22 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10873595

Title: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family.

PubMed ID: 10873595

DOI: 10.1006/bbrc.2000.2922

PubMed ID: 11316767

Title: Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner.

PubMed ID: 11316767

DOI: 10.1210/endo.142.5.8115

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

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: 12409283

Title: Characterization and identification of steroid sulfate transporters of human placenta.

PubMed ID: 12409283

DOI: 10.1152/ajpendo.00257.2002

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19129463

Title: Mechanisms of pH-gradient driven transport mediated by organic anion polypeptide transporters.

PubMed ID: 19129463

DOI: 10.1152/ajpcell.00436.2008

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 30343886

Title: Estrone sulphate uptake by the microvillous membrane of placental syncytiotrophoblast is coupled to glutamate efflux.

PubMed ID: 30343886

DOI: 10.1016/j.bbrc.2018.10.074

PubMed ID: 35307651

Title: Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier.

PubMed ID: 35307651

DOI: 10.1124/dmd.121.000748

Sequence Information:

  • Length: 722
  • Mass: 77193
  • Checksum: DD8F0C10E4BCD255
  • Sequence:
    • MPLHQLGDKP LTFPSPNSAM ENGLDHTPPS RRASPGTPLS PGSLRSAAHS PLDTSKQPLC 
QLWAEKHGAR GTHEVRYVSA GQSVACGWWA FAPPCLQVLN TPKGILFFLC AAAFLQGMTV 
NGFINTVITS LERRYDLHSY QSGLIASSYD IAACLCLTFV SYFGGSGHKP RWLGWGVLLM 
GTGSLVFALP HFTAGRYEVE LDAGVRTCPA NPGAVCADST SGLSRYQLVF MLGQFLHGVG 
ATPLYTLGVT YLDENVKSSC SPVYIAIFYT AAILGPAAGY LIGGALLNIY TEMGRRTELT 
TESPLWVGAW WVGFLGSGAA AFFTAVPILG YPRQLPGSQR YAVMRAAEMH QLKDSSRGEA 
SNPDFGKTIR DLPLSIWLLL KNPTFILLCL AGATEATLIT GMSTFSPKFL ESQFSLSASE 
AATLFGYLVV PAGGGGTFLG GFFVNKLRLR GSAVIKFCLF CTVVSLLGIL VFSLHCPSVP 
MAGVTASYGG SLLPEGHLNL TAPCNAACSC QPEHYSPVCG SDGLMYFSLC HAGCPAATET 
NVDGQKVYRD CSCIPQNLSS GFGHATAGKC TSTCQRKPLL LVFIFVVIFF TFLSSIPALT 
ATLRCVRDPQ RSFALGIQWI VVRILGGIPG PIAFGWVIDK ACLLWQDQCG QQGSCLVYQN 
SAMSRYILIM GLLYKVLGVL FFAIACFLYK PLSESSDGLE TCLPSQSSAP DSATDSQLQS 
SV