SLC5A5 (Solute Carrier Family 5 Member 5) - Sodium/Iodide Symporter
A key transporter for iodide uptake, essential for thyroid hormone synthesis and linked to thyroid dysgenesis and cancer.
Gene Information Card
| Symbol | SLC5A5 |
|---|---|
| Full Name | Solute Carrier Family 5 Member 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.11 |
| NCBI Gene ID | 6528 ncbi.nlm.nih.gov/gene/6528 |
| Ensembl ID | ENSG00000105641 |
| UniProt ID | Q92911 |
| OMIM ID | 601843 |
| HGNC ID | 11040 |
| Aliases | NIS, NIS1, SMIT, TDH1 |
Description
The SLC5A5 gene encodes the sodium/iodide symporter (NIS), a transmembrane glycoprotein that mediates active iodide transport into thyroid follicular cells, a critical step in thyroid hormone biosynthesis. NIS is also expressed in other tissues such as salivary glands, gastric mucosa, and lactating mammary glands, where it facilitates iodide secretion. Mutations in SLC5A5 can lead to iodide transport defect, causing congenital hypothyroidism, while its expression is often dysregulated in thyroid cancer, making it a target for radioiodine therapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital hypothyroidism (iodide transport defect) | Loss-of-function mutations impair iodide uptake, reducing thyroid hormone synthesis. | OMIM #601843; ClinVar |
| Thyroid cancer (papillary and follicular) | Reduced NIS expression leads to poor radioiodine uptake, complicating treatment. | COSMIC; PubMed studies |
| Autoimmune thyroiditis | NIS may be an autoantigen; antibodies can inhibit iodide transport. | PubMed studies |
| Sialadenitis (radiation-induced) | NIS expression in salivary glands can lead to iodide accumulation and damage during radioiodine therapy. | PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thyroid | High (nTPM ~ 200) | High expression; primary site of iodide uptake. |
| Salivary gland | Moderate (nTPM ~ 50) | Iodide secretion into saliva. |
| Stomach | Low (nTPM ~ 10) | Gastric mucosa expression. |
| Mammary gland (lactating) | Low (nTPM ~ 5) | Iodide transport into milk. |
| Kidney | Low (nTPM ~ 3) | Renal iodide reabsorption. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Thyroid follicular cells | High | Primary site of NIS expression. |
| MCF7 (breast cancer) | Low | Expression induced by lactogenic hormones. |
| Caco-2 (colon cancer) | Low | Gastric-like expression. |
| HeLa (cervical cancer) | Not detected | No significant expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1143G>A (p.Trp381Ter) | Nonsense | Rare (found in few families) | Truncated protein, loss of function. |
| c.1940C>T (p.Pro647Leu) | Missense | Rare | Impaired trafficking to plasma membrane. |
| c.1197G>A (p.Gly395Arg) | Missense | Rare | Reduced iodide transport activity. |
| c.1540G>A (p.Gly514Ser) | Missense | Rare | Loss of function, associated with thyroid dyshormonogenesis. |
Mutation functional classification
Loss of Function (LOF)
Most SLC5A5 mutations are loss-of-function, leading to iodide transport defect and congenital hypothyroidism.
Gain of Function (GOF)
No gain-of-function mutations reported; overexpression in cancer is not due to activating mutations.
Dominant Negative (DN)
No dominant-negative effects reported; SLC5A5 mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • sodium:iodide symporter activity | • iodide transmembrane transporter activity |
| • sodium ion transmembrane transporter activity | • plasma membrane |
| • integral component of membrane | • iodide transport |
| • sodium ion transport | • thyroid hormone generation |
Pathways
• Thyroid hormone synthesis
• Iodide metabolism
• Solute carrier (SLC) transporter family
Protein Summary
The sodium/iodide symporter (NIS) is a 13-transmembrane domain glycoprotein of ~643 amino acids. It couples the inward translocation of sodium ions (down its electrochemical gradient) to the uptake of iodide, achieving intracellular iodide concentrations 20-40 times higher than plasma. NIS is primarily localized to the basolateral membrane of thyroid follicular cells. Its activity is stimulated by TSH via cAMP signaling. In addition to iodide, NIS can transport other anions like perchlorate and thiocyanate, which are competitive inhibitors. Post-translational modifications, including glycosylation, are essential for proper membrane trafficking and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC5A5 Knockout HEK293 Cell Line | EDJ-KQ5768 | Human | 6528 | Details Get a Quote |
| SLC5A5 Knockout HeLa Cell Line | EDJ-KQ54489 | Human | 6528 | Details Get a Quote |
| SLC5A5 Knockout A-549 Cell Line | EDJ-KQ62975 | Human | 6528 | Details Get a Quote |
| SLC5A5 Knockout HCT 116 Cell Line | EDJ-KQ71446 | Human | 6528 | Details Get a Quote |
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