Details for: SLC5A5

Gene ID: 6528

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: SLC5A5

Ensembl ID: ENSG00000105641

Description: solute carrier family 5 member 5

Cell Significance Landscape

Associated with

Significant Cells

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

  • foveolar cell of stomach CL0002179
    CSI 9.74
    rCSI 20.74%
    PRS 98.78
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.81
    rCSI 3.73%
    PRS 99.28
  • choroid plexus epithelial cell CL0000706
    CSI 3.95
    rCSI 6.47%
    PRS 96.9
  • chondrocyte CL0000138
    CSI 2.96
    rCSI 4.71%
    PRS 97.22
  • retinal pigment epithelial cell CL0002586
    CSI 2.13
    rCSI 4.23%
    PRS 97.27

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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    • High
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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 [SLC5A5](/details-gene/6528), or Solute Carrier Family 5 Member 5, encodes the sodium-iodide symporter (NIS), a transmembrane protein essential for iodide uptake from the bloodstream. Its primary and most well-characterized function is in the thyroid gland, where it facilitates the first and rate-limiting step in the biosynthesis of thyroid hormones. Consistent with this role, mutations in [SLC5A5](/details-gene/6528) are a known cause of congenital hypothyroidism, specifically thyroid dyshormonogenesis type 1 ([274400](https://omim.org/entry/274400)). While its function in thyroid physiology is established, expression data indicates a significant presence in various other specialized epithelial tissues. **Overall**, its most significant expression is observed in the `[foveolar cell of stomach](/details-cell/CL0002179)`, with notable expression also found in the `[epithelial cell of lower respiratory tract](/details-cell/CL0002632)` and `[choroid plexus epithelial cell](/details-cell/CL0000706)`, suggesting broader roles in ion transport and barrier functions across multiple organ systems. ## Cellular Roles and Expression Landscape The canonical role of [SLC5A5](/details-gene/6528) is as a key functional protein in thyroid follicular cells, where it actively transports iodide into the cell, a process critical for hormone synthesis. This function is heavily supported by extensive literature and its direct linkage to congenital hypothyroidism `[Link](https://doi.org/10.1038/ng0697-124)`. However, the provided expression data broadens this view. **Overall**, the highest cellular significance for [SLC5A5](/details-gene/6528) is not in thyroid cells but in the `[foveolar cell of stomach](/details-cell/CL0002179)` (CSI: 9.74), which are mucus-producing cells lining the stomach. This suggests a potentially important, non-thyroidal role in the gastrointestinal tract. The gene also shows significant expression in a variety of other specialized epithelial cells, many of which are associated with physiological barriers. These include the `[epithelial cell of lower respiratory tract](/details-cell/CL0002632)`, the `[choroid plexus epithelial cell](/details-cell/CL0000706)` of the blood-cerebrospinal fluid barrier, and the `[retinal pigment epithelial cell](/details-cell/CL0002586)` of the blood-retina barrier. This expression pattern is consistent with a specialized function in iodide transport or ion homeostasis in secretory and barrier tissues beyond the thyroid gland. ## Pathways and Molecular Function [SLC5A5](/details-gene/6528) functions as an integral plasma membrane protein with `[sodium:iodide symporter activity](/details-go/GO:0008507)`, co-transporting two sodium ions for each iodide ion. This symporter activity is the central mechanism for `[iodide transport](/details-go/GO:0015705)`. The protein is known to exist and function as a homodimer, as supported by its annotated `[protein homodimerization activity](/details-go/GO:0042803)` and experimental evidence `[Link](https://doi.org/10.1089/thy.2019.0034)`. This molecular function is a critical component of the `[Thyroxine biosynthesis](/reactome/R-HSA-209968)` pathway, which ultimately leads to `[thyroid hormone generation](/details-go/GO:0006590)`. The gene's expression and activity are regulated by thyroid-stimulating hormone (TSH), as indicated by its involvement in the `[cellular response to thyroid stimulating hormone](/details-go/GO:1904401)` `[Link](https://doi.org/10.1210/jcem.82.10.4269)`. Pathologically, defects in this transporter are directly linked to the Reactome pathway `[Defective slc5a5 causes thyroid dyshormonogenesis 1 (tdh1)](/reactome/R-HSA-5619096)`, underscoring its clinical importance in endocrine function. Its expression in the choroid plexus is consistent with its annotated role in `[Transport across blood-brain barrier](/details-go/GO:0150104)`. ## Research Directions The well-established role of [SLC5A5](/details-gene/6528) in thyroid function contrasts with its high expression in non-thyroidal tissues, presenting key areas for future investigation. **Proposed Hypotheses:** 1. The high expression of [SLC5A5](/details-gene/6528) in `[foveolar cell of stomach](/details-cell/CL0002179)` suggests a physiological role in gastric iodide concentration. This trapped iodide may be secreted into the gastric lumen and oxidized to form hypoiodite, a potent antimicrobial agent, thereby contributing to the innate defense against gastric pathogens. 2. The significant expression in `[choroid plexus epithelial cell](/details-cell/CL0000706)` indicates that [SLC5A5](/details-gene/6528) actively regulates iodide levels within the cerebrospinal fluid. This transport may be crucial for normal brain development and neuronal function, as iodide is a necessary component of thyroid hormones that are vital for neurogenesis. **Key Experimental Approach:** To test the first hypothesis regarding the role of [SLC5A5](/details-gene/6528) in gastric defense, a conditional knockout mouse model could be developed to specifically delete the gene in gastric foveolar cells. Following deletion, iodide levels in gastric juice could be quantified using inductively coupled plasma mass spectrometry (ICP-MS). The composition of the gastric microbiome could be analyzed via 16S rRNA sequencing to assess dysbiosis. Furthermore, these knockout mice and wild-type controls could be challenged with a common gastric pathogen, such as *Helicobacter pylori*, to determine if the absence of gastric [SLC5A5](/details-gene/6528) leads to increased bacterial colonization and more severe gastritis. **Therapeutic Potential:** [SLC5A5](/details-gene/6528) is already a cornerstone of thyroid cancer therapy. Its unique ability to concentrate iodide in thyroid cells is exploited for targeted radionuclide therapy, where radioactive iodine (I-131) is administered to ablate residual thyroid tissue or destroy metastatic thyroid cancer cells. Its function also makes it a target for diagnostic imaging. Rather than direct inhibition or activation, its therapeutic potential lies in using its transport activity as a "Trojan horse" to deliver cytotoxic agents specifically to cells that express it. For congenital hypothyroidism caused by loss-of-function mutations, future gene therapy approaches aimed at restoring functional [SLC5A5](/details-gene/6528) expression in the thyroid gland could represent a potential cure.

Genular Protein ID: 1706231399

Symbol: SC5A5_HUMAN

Name: Sodium/iodide cotransporter

UniProtKB Accession Codes:

Q92911 O43702 Q2M335 Q9NYB6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 10 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 EMBL 6 Ensembl 1 GO 20 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 Rhea 5 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 8806637

Title: Cloning of the human sodium iodide symporter.

PubMed ID: 8806637

DOI: 10.1006/bbrc.1996.1358

PubMed ID: 9329364

Title: Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue.

PubMed ID: 9329364

DOI: 10.1210/jcem.82.10.4269

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 20797386

Title: Characterisation of the purified human sodium/iodide symporter reveals that the protein is mainly present in a dimeric form and permits the detailed study of a native C-terminal fragment.

PubMed ID: 20797386

DOI: 10.1016/j.bbamem.2010.08.013

PubMed ID: 12488351

Title: Anion selectivity by the sodium iodide symporter.

PubMed ID: 12488351

DOI: 10.1210/en.2002-220744

PubMed ID: 18372236

Title: Comparison of expressed human and mouse sodium/iodide symporters reveals differences in transport properties and subcellular localization.

PubMed ID: 18372236

DOI: 10.1677/joe-07-0455

PubMed ID: 18708479

Title: Histidine residue at position 226 is critical for iodide uptake activity of human sodium/iodide symporter.

PubMed ID: 18708479

DOI: 10.1677/joe-08-0249

PubMed ID: 31310151

Title: Dimerization of the Sodium/Iodide Symporter.

PubMed ID: 31310151

DOI: 10.1089/thy.2019.0034

PubMed ID: 32084174

Title: Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS).

PubMed ID: 32084174

DOI: 10.1371/journal.pone.0229085

PubMed ID: 9171822

Title: Congenital hypothyroidism caused by a mutation in the Na(+)/I(-) symporter.

PubMed ID: 9171822

DOI: 10.1038/ng0697-124

PubMed ID: 9745458

Title: Novel, missense and loss-of-function mutations in the sodium/iodide symporter gene causing iodide transport defect in three Japanese patients.

PubMed ID: 9745458

DOI: 10.1210/jcem.83.9.5245

PubMed ID: 9486973

Title: Congenital hypothyroidism due to mutations in the sodium/iodide symporter: identification of a nonsense mutation producing a downstream cryptic 3' splice site.

PubMed ID: 9486973

DOI: 10.1172/jci1504

PubMed ID: 10487695

Title: A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect.

PubMed ID: 10487695

DOI: 10.1210/jcem.84.9.5971

Sequence Information:

  • Length: 643
  • Mass: 68666
  • Checksum: 02D361A27B2FDA43
  • Sequence:
    • MEAVETGERP TFGAWDYGVF ALMLLVSTGI GLWVGLARGG QRSAEDFFTG GRRLAALPVG 
LSLSASFMSA VQVLGVPSEA YRYGLKFLWM CLGQLLNSVL TALLFMPVFY RLGLTSTYEY 
LEMRFSRAVR LCGTLQYIVA TMLYTGIVIY APALILNQVT GLDIWASLLS TGIICTFYTA 
VGGMKAVVWT DVFQVVVMLS GFWVVLARGV MLVGGPRQVL TLAQNHSRIN LMDFNPDPRS 
RYTFWTFVVG GTLVWLSMYG VNQAQVQRYV ACRTEKQAKL ALLINQVGLF LIVSSAACCG 
IVMFVFYTDC DPLLLGRISA PDQYMPLLVL DIFEDLPGVP GLFLACAYSG TLSTASTSIN 
AMAAVTVEDL IKPRLRSLAP RKLVIISKGL SLIYGSACLT VAALSSLLGG GVLQGSFTVM 
GVISGPLLGA FILGMFLPAC NTPGVLAGLG AGLALSLWVA LGATLYPPSE QTMRVLPSSA 
ARCVALSVNA SGLLDPALLP ANDSSRAPSS GMDASRPALA DSFYAISYLY YGALGTLTTV 
LCGALISCLT GPTKRSTLAP GLLWWDLARQ TASVAPKEEV AILDDNLVKG PEELPTGNKK 
PPGFLPTNED RLFFLGQKEL EGAGSWTPCV GHDGGRDQQE TNL