SLC5A5 Gene

HGNC Family Solute carriers (SLC)
Name solute carrier family 5 (sodium/iodide cotransporter), member 5
Description This gene encodes a member of the sodium glucose cotransporter family. The encoded protein is responsible for the uptake of iodine in tissues such as the thyroid and lactating breast tissue. The iodine taken up by the thyroid is incorporated into the metabolic regulators triiodothyronine (T3) and tetraiodothyronine (T4). Mutations in this gene are associated with thyroid dyshormonogenesis 1.[provided by RefSeq, Sep 2009]
Summary
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In addition to its central role in thyroid physiology, NIS is expressed in extrathyroidal tissues such as the salivary gland, gastric mucosa, and lactating mammary gland, where it contributes to iodide accumulation and is exploited for both diagnostic imaging and targeted radioiodine therapies in benign and malignant conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNumerous studies have elucidated the regulation of NIS expression and function. Hormonal regulators such as TSH can stimulate NIS gene transcription and enhance trafficking to the plasma membrane, while agents including retinoic acid and histone deacetylase inhibitors serve to “redifferentiate” thyroid tumors by modulating NIS expression. In thyroid and breast cancers, however, aberrant expression, intracellular mislocalization, defective glycosylation, and epigenetic modifications (for example, CpG island promoter hypermethylation) are frequently observed, correlating with reduced iodide uptake and diminished effectiveness of radioiodine treatment. In addition, microRNAs (e.g. miR-146b) and oncogenic signaling pathways (including those driven by BRAFV600E) have been implicated in the repression of NIS, suggesting that both transcriptional and posttranscriptional mechanisms influence its activity in cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "23"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its endogenous role in iodide metabolism, SLC5A5 has attracted considerable attention as a vehicle for therapeutic gene transfer and targeted radiotherapy—not only in differentiated thyroid cancer but also in extrathyroidal malignancies such as breast and hepatocellular carcinomas. Advances in our understanding of NIS’s structure–function relationships have revealed critical aspects of its plasma membrane targeting and intracellular trafficking, with regulatory partners including ARF4, VCP, and PBF influencing its cellular distribution and activity. Moreover, clinical strategies that aim to restore or enhance NIS expression through epigenetic modulation, manipulation of microRNA networks, or gene therapy approaches hold promise for overcoming radioiodine resistance in dedifferentiated tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Irene L Wapnir, Matt van de Rijn, Kent Nowels, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A novel peculiar mutation in the sodium/iodide symporter gene in spanish siblings with iodide transport defect."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jcem.87.8.8767"}], "href": "https://doi.org/10.1210/jcem.87.8.8767"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12161518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12161518"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Wenjing Li, Juan Pablo Nicola, L Mario Amzel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Asn441 plays a key role in folding and function of the Na+/I- symporter (NIS)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.13-229138"}], "href": "https://doi.org/10.1096/fj.13-229138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23650190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23650190"}]}]}]}
Synonyms NIS, TDH1
Proteins SC5A5_HUMAN
NCBI Gene ID 6528
API
Download Associations
Predicted Functions View SLC5A5's ARCHS4 Predicted Functions.
Co-expressed Genes View SLC5A5's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View SLC5A5's ARCHS4 Predicted Functions.

Functional Associations

SLC5A5 has 5,084 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 104 datasets.

Click the + buttons to view associations for SLC5A5 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of SLC5A5 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of SLC5A5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of SLC5A5 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of SLC5A5 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of SLC5A5 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of SLC5A5 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of SLC5A5 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of SLC5A5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with SLC5A5 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC5A5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of SLC5A5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of SLC5A5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
ClinVar Gene-Phenotype Associations phenotypes associated with SLC5A5 gene from the curated ClinVar Gene-Phenotype Associations dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of SLC5A5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing SLC5A5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing SLC5A5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with SLC5A5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with SLC5A5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of SLC5A5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with SLC5A5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with SLC5A5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with SLC5A5 gene/protein from the curated CTD Gene-Disease Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by SLC5A5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Curated Gene-Disease Association Evidence Scores diseases involving SLC5A5 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving SLC5A5 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with SLC5A5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with SLC5A5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with SLC5A5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with SLC5A5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at SLC5A5 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC5A5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of SLC5A5 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing SLC5A5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of SLC5A5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with SLC5A5 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing SLC5A5 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of SLC5A5 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of SLC5A5 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of SLC5A5 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of SLC5A5 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of SLC5A5 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of SLC5A5 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving SLC5A5 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving SLC5A5 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving SLC5A5 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing SLC5A5 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing SLC5A5 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing SLC5A5 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by SLC5A5 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by SLC5A5 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by SLC5A5 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of SLC5A5 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of SLC5A5 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of SLC5A5 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GWASdb SNP-Disease Associations diseases associated with SLC5A5 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with SLC5A5 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of SLC5A5 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HMDB Metabolites of Enzymes interacting metabolites for SLC5A5 protein from the curated HMDB Metabolites of Enzymes dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of SLC5A5 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of SLC5A5 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of SLC5A5 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of SLC5A5 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HPO Gene-Disease Associations phenotypes associated with SLC5A5 gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for SLC5A5 from the curated Hub Proteins Protein-Protein Interactions dataset.
HuBMAP ASCT+B Annotations cell types associated with SLC5A5 gene from the HuBMAP ASCT+B dataset.
HuBMAP ASCT+B Augmented with RNA-seq Coexpression cell types associated with SLC5A5 gene from the HuBMAP ASCT+B Augmented with RNA-seq Coexpression dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by SLC5A5 gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for SLC5A5 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of SLC5A5 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Kinase Library Serine Threonine Kinome Atlas kinases that phosphorylate SLC5A5 protein from the Kinase Library Serine Threonine Atlas dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of SLC5A5 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with SLC5A5 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of SLC5A5 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of SLC5A5 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain SLC5A5 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by SLC5A5 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting SLC5A5 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of SLC5A5 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of SLC5A5 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of SLC5A5 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing SLC5A5 protein recovered by IP-MS from the NURSA Protein Complexes dataset.
OMIM Gene-Disease Associations phenotypes associated with SLC5A5 gene from the curated OMIM Gene-Disease Associations dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for SLC5A5 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of SLC5A5 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of SLC5A5 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving SLC5A5 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving SLC5A5 protein from the Wikipathways PFOCR 2024 dataset.
Phosphosite Textmining Biological Term Annotations biological terms co-occuring with SLC5A5 protein in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset.
Reactome Pathways 2014 pathways involving SLC5A5 protein from the Reactome Pathways dataset.
Reactome Pathways 2024 pathways involving SLC5A5 protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of SLC5A5 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at SLC5A5 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of SLC5A5 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of SLC5A5 gene from the RummaGEO Gene Perturbation Signatures dataset.
SILAC Phosphoproteomics Signatures of Differentially Phosphorylated Proteins for Drugs drug perturbations changing phosphorylation of SLC5A5 protein from the SILAC Phosphoproteomics Signatures of Differentially Phosphorylated Proteins for Drugs dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of SLC5A5 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of SLC5A5 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of SLC5A5 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of SLC5A5 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of SLC5A5 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with SLC5A5 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with SLC5A5 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving SLC5A5 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving SLC5A5 protein from the WikiPathways Pathways 2024 dataset.