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SLC5A5 (solute carrier family 5 (sodium iodide symporter), member 5)

Written2009-07Julie Di Bernardo, Kerry J Rhoden
Medical Genetics Unit, Department of Gynaecologic, Obstetric, Pediatric Sciences, University of Bologna, Bologna, Italy

(Note : for Links provided by Atlas : click)


HGNC (Hugo) SLC5A5
HGNC Alias symbNIS
HGNC Previous name"solute carrier family 5 (sodium iodide symporter), member 5
 solute carrier family 5 (sodium/iodide cotransporter), member 5"
LocusID (NCBI) 6528
Atlas_Id 44476
Location 19p13.11  [Link to chromosome band 19p13]
Location_base_pair Starts at 17871945 and ends at 17895174 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping SLC5A5.png]
Local_order Telomeric to CCDC124, centromeric to JAK3.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
SYAP1 (Xp22.2) / SLC5A5 (19p13.11)


Note The SLC5A5 gene was first sequenced in 1996 from rat and subsequently human thyroid (Dai et al., 1996; Smanik et al., 1996) and the exon-intron organization characterized in 1997 (Smanik et al., 1997).
Description 15 exons, spanning 23202 bp.
Transcription Transcription starts at -375 relative to the ATG site. The minimal promoter is localized to a region of 144 bp that includes a 90-bp stretch (-478 and -389 bp) with 73% identity to the rat NIS proximal promoter and containing a TATA- and a GC-box. The region between -596 and -415 is essential for full promoter activity in human thyroid cells. A human NIS gene 5' far-upstream enhancer (hNUE) (-9847 to -8968) confers thyroid-specific and TSH-cAMP responsive transcription and contains an essential Pax-8 binding site and a cAMP response element (CRE)-like sequence activated by a CRE modulator (CREM) (Taki et al., 2002; Fenton et al., 2008).
RNA: 3576 bases, open reading frame: 1929 bp. No splice variants are reported.
Pseudogene No pseudogenes have been identified.


Note The protein encoded by the SLC5A5 gene is more commonly referred to in the scientific literature as the Sodium Iodide Symporter or NIS.
  The diagram has been drawn following UniProtKB/Swiss-Prot database prediction and maintaining approximate length proportions among extracellular and intracellular segments. Transmembrane segments are represented by green rectangles, N-glycosylation sites in yellow.
Description NIS is a glycoprotein with 643 aa and predicted molecular weight 69k Da. It is composed of 13 transmembrane domains, an extracellular N-terminal, a cytosolic C-terminal and three N-linked glycosylation sites at positions 225, 485 and 497. NIS is phosphorylated in vivo, mostly at the level of serines.
Expression NIS is highly expressed and is active in the thyroid, stomach, salivary glands and lactating mammary gland. Low levels of NIS have also been detected by immunohistochemistry and/or RT-PCR in other extrathyroidal tissues (small intestine, colon, rectum, pancreas, kidney, bile duct, lung, lacrimal gland, heart, placenta, testis, ovaries, prostate gland, adrenal gland, thymus and pituitary gland), but it is not clear to what extent it is active in these tissues.
Localisation Cell membrane. NIS is located on the basolateral membrane of thyroid follicular cells, lactating mammary gland alveolar cells, salivary gland ductal epithelial cells and gastric mucin-secreting cells. In contrast, NIS is located on the apical membrane of placental trophoblasts and enterocytes. In the kidney, NIS has a diffuse cytoplasmic distribution in distal tubular cells, but is more prominent in the basolateral aspect of proximal tubular cells.
Function NIS mediates the transport of iodide (I-) into cells; it cotransports Na+ and I- on a 2:1 basis, using the inwardly directed Na+ concentration gradient generated by the Na+-K+ ATPase to concentrate I- to 30-50 times the extracellular concentration.
The major function of NIS is to concentrate I- in the thyroid for the synthesis of thyroid hormones triiodothyronine (T3) and tetraiodothyronine (T4). Iodine, a trace element obtained with the diet, is organified into the thyroid hormone precursor thyroglobulin by thyroid peroxidase in the presence of hydrogen peroxide. Thyroidal NIS is regulated by thyroid stimulating hormone (TSH) under control of the hypothalamic-pituitary axis. Low circulating levels of T3 and T4 stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus, which in turn stimulates the secretion of TSH from the anterior pituitary gland. TSH increases NIS expression resulting in enhanced I- uptake and thyroid hormone synthesis. In contrast, high levels of circulating T3 and T4 inhibit TSH production through a negative feedback loop reducing iodide uptake and thyroid hormone production. TSH regulates NIS transcription via a cAMP-dependent pathway requiring binding of transcription factors Pax-8 and CREM to the hNUE enhancer element. TSH also regulates NIS trafficking, promoting NIS targeting to the plasma membrane.
Mammary gland NIS drives the secretion of I- into milk in fulfillment of the newborn's dietary requirement for iodine and is induced by lactogenic hormones (prolactin, oxytocin).
Placental NIS may provide the fetus with the necessary I- to synthesize thyroid hormones.
NIS function in other tissues is unclear. I- secretion may play a role in mucosal host defense through the formation of reactive metabolites of iodine with antimicrobial activity. A role for NIS in the transport of thiocyanate and nitrate across mucosal barriers has also been proposed, again resulting in the formation of antimicrobial molecules.
Homology NIS belongs to the SLC superfamily of solute carriers. The SLC5 family has 12 members to date (SLC5A1-SLC5A12) and includes Na+-coupled cotransporters that rely on the Na+ electrochemical gradient to drive solute transport into cells. NIS (SLC5A) has the highest homology with SLC5A12 (48% identity) and SLC5A8 (46% identity), both of which are thought to be sodium/monocarboxylate transporters and SLC5A6 (42% identity), a sodium/multivitamin transporter.


  Localisation of NIS mutations identified in iodide transport defect (ITD) (in red) and thyroid follicular adenoma (in blue).
Germinal Germinal NIS mutations cause Iodide Transport Defect (ITD), a rare form of dyshormogenic congenital hypothyroidism with autosomal recessive inheritance (OMIM 274400). Twelve loss-of-function mutations have been reported to date: V59E, G93R, R124H, ΔM143-Q323, Q267E, C272X, T354P, G395R, ΔA439-P443, frame-shift 515X, Y531X, G543E. Mutations reduce thyroidal iodide uptake as a result of impaired NIS expression, maturation, trafficking or transport activity.
Somatic A loss-of-function deletion of exon 6 was identified in a single case of follicular thyroid adenoma (Liang et al., 2005). No other somatic mutations have been reported in association with cancer.

Implicated in

Entity Thyroid cancer
Disease NIS-mediated uptake of radionuclides has long been exploited in diagnostic scintigraphic imaging (123I, 131I, 99mTcO4-) and radiotherapy (131I) of thyroid carcinoma of follicular cell origin. Compared to other cancers, the prevalence of thyroid cancer is relatively low and its prognosis after surgery and radioiodine therapy is mostly favorable. However, radioiodine uptake is frequently decreased in differentiated thyroid carcinoma (papillary and follicular) and is completely absent in 20% of differentiated carcinomas and most anaplastic thyroid carcinomas. Furthermore, the recurrence rate of thyroid cancer is high (10-30% for papillary thyroid carcinoma) and only one third of patients with distant metastases respond to 131I therapy with complete remission.
NIS expression in thyroid cancer is controversial with reports of under-expression as well as over-expression (Arturi et al., 1998; Saito et al., 1998; Venkataraman et al., 1999; Lazar et al., 1999; Castro et al., 2001; Dohan et al., 2001; Ward et al., 2003; Trouttet-Masson et al., 2004). Low NIS expression identifies aggressive thyroid tumors and correlates with reduced radioiodine uptake and tumor dedifferentiation. Loss of NIS expression may be associated with hypermethylation of the NIS gene promoter, or may be secondary to reduced expression of nuclear transcription factors. When over-expressed, NIS is mostly intracellular suggesting defective targeting of the protein to the plasma membrane in these cases. Hypofunctioning thyroid tumors express low levels of non-glycosylated NIS suggesting that protein maturation may also be impaired.
Several pharmacological approaches are being tested for their ability to promote cellular re-differentiation, increase endogenous NIS expression and restore iodide transport in thyroid carcinoma cell lines and in patients. Agents include retinoic acid, demethylating agents, histone deacetylase inhibitors and reverse transcriptase inhibitors (Schmutzler et al., 1997; Venkataraman et al., 1999; Zarnegar et al., 2002; Fortunati et al., 2004; Landriscina et al., 2005). The effectiveness of these agents, however, is variable and their clinical utility has yet to be proven.
Oncogenesis Although no somatic NIS mutations have been identified in thyroid carcinoma, alterations in other genes or gene products may be associated with NIS impairment.
BRAF: Papillary thyroid carcinomas (PTC) harboring the BRAF V600E mutation have reduced NIS expression and impaired targeting to the plasma membrane, which correlates with reduced radioiodine uptake and high risk of recurrence (Riesco-Eizagirre et al., 2006). BRAF V600E-positive PTC also have reduced expression of other thyroid-specific genes such as thyroperoxidase and thyroglobulin, suggesting that impaired NIS expression may be part of an early dedifferentiation process present at the molecular level in BRAF V600E-mutated PTC (Durante et al., 2007; Romei et al., 2008).
RET/PTC: Expression of RET/PTC rearrangements reduces radioiodide uptake and NIS expression in thyroid cells in vitro and transgenic mice (Cho et al., 1999; Knauf et al., 2003). No change in NIS expression, however, was detected in papillary thyroid carcinoma with RET/PTC rearrangements (Romei et al., 2008).
PTTG: Differentiated thyroid cancer over-expresses pituitary tumor transforming gene (PTTG), a proto-oncogene involved in the control of sister chromatid separation. PTTG overexpression correlates with reduced radioiodine uptake and is a prognostic factor for persistent disease (Saez et al., 2006). PTTG downregulates NIS expression and I- uptake in vitro, possibly by repressing the binding of transcriptional regulators to the hNUE upstream enhancer (Boelaert et al., 2007).
Entity Breast cancer
Disease NIS is up-regulated in breast cancer and attention has recently focused on the potential application of radioiodine in the diagnosis and therapy of breast cancer. Several studies have detected NIS immunohistochemically in 30-90% of primary and metastatic breast carcinomas, with variable degrees of intracellular and plasma membrane staining (Tazebay et al, 2000; Wapnir et al, 2003; Wapnir et al., 2004; Beyer et al., 2008; Renier et al., 2009). Estimates of NIS expression in breast cancer, however, may be overestimated due to non-specific binding of some anti-NIS antibodies resulting in a diffuse intracellular staining. One study failed to detect significant NIS immunostaining in 30 cases of primary breast cancer (Peyrottes et al., 2009). In vivo scintigraphic imaging detected 123I or 99mTcO4 uptake in up to 25% of NIS-expressing breast tumors, suggesting that the expression of functional NIS in breast cancer is low (Moon et al., 2001; Wapnir et al., 2004). Current research is aimed at identifying strategies that increase the expression and membrane targeting of NIS in breast cancer, in order to improve the efficiency of NIS-mediated radionuclide uptake.
Entity Cholangiocarcinoma (CCA)
Disease NIS is up-regulated in CCA and is localized to the plasma membrane and/or cytoplasm of bile duct epithelial cholangiocytes. In the diethylnitrosamine rat model of liver cancer, NIS is expressed at the preneoplastic stages of liver carcinogenesis and enables tumor suppression after 131I radiotherapy (Liu et al., 2007). Radioiodide therapy may therefore represent a novel strategy for the treatment of CCA.
Entity Gastric cancer
Disease NIS expression, normally present in the gastric mucosa, is markedly decreased or absent in gastric cancer (Altorjay et al., 2007) and distinguishes malignant from benign gastric lesions (Farnedi et al., 2009).
Entity Various carcinomas
Note Targeted NIS gene therapy is being evaluated as a potential diagnostic and therapeutic option for various cancers, enabling tumor cells to accumulate NIS-transported radionuclides. Preclinical studies demonstrate NIS expression, radioiodide uptake and tumor cell death in vitro and in vivo following targeted adenoviral NIS gene transfer to tumor cells. A phase I clinical trial is ongoing to study the efficacy and safety of NIS gene therapy and radioactive iodine for the treatment of prostate cancer (NCT00788307,
Disease Carcinomas of the prostate, cervix, breast, head and neck, lung, liver, thyroid, colon, ovaries and pancreas; myeloma; glioma.
Entity Thyroid adenoma
Disease Benign nonfunctioning thyroid adenomas are characterized by reduced radioiodine uptake due to reduced NIS expression or defective targeting of NIS to the plasma membrane (Tonacchera et al., 2002). A loss-of-function deletion of exon 6 of the NIS gene was identified in a single case of follicular thyroid adenoma (Liang et al., 2005). Hyperfunctioning toxic adenomas harbor activating mutations of the TSH receptor and are characterized by increased NIS expression with correct plasma membrane localization (Lazar et al., 1999).
Entity Congenital Hypothyroidism
Disease Germinal NIS mutations causing iodide transport defect (ITD) are a rare cause of dyshormogenic congenital hypothyroidism (OMIM 274400). To date, 12 mutations have been reported (V59E, G93R, R124H, ΔM143-Q323, Q267E, C272X, T354P, G395R, ΔA439-P443, frame-shift 515X, Y531X, G543E) leading to reduced or absent thyroidal radioiodine uptake, low iodide saliva: plasma ratios and a variable degree of hypothyroidism and goiter.
Prognosis Goitre, severe neuro-developmental impairment and infertility if not treated. Hypothyroidism treated with T4-replacement therapy and I- supplementation.


Expression of the Na+/I- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus.
Altorjay A, Dohan O, Szilagyi A, Paroder M, Wapnir IL, Carrasco N.
BMC Cancer. 2007 Jan 10;7:5.
PMID 17214887
Iodide symporter gene expression in human thyroid tumors.
Arturi F, Russo D, Schlumberger M, du Villard JA, Caillou B, Vigneri P, Wicker R, Chiefari E, Suarez HG, Filetti S.
J Clin Endocrinol Metab. 1998 Jul;83(7):2493-6.
PMID 9661633
Cloning of a functional promoter of the human sodium/iodide-symporter gene.
Behr M, Schmitt TL, Espinoza CR, Loos U.
Biochem J. 1998 Apr 15;331 ( Pt 2):359-63.
PMID 9531470
Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer?
Beyer SJ, Jimenez RE, Shapiro CL, Cho JY, Jhiang SM.
Breast Cancer Res Treat. 2009 May;115(1):205-12.
PMID 18500672
PTTG and PBF repress the human sodium iodide symporter.
Boelaert K, Smith VE, Stratford AL, Kogai T, Tannahill LA, Watkinson JC, Eggo MC, Franklyn JA, McCabe CJ.
Oncogene. 2007 Jun 28;26(30):4344-56.
PMID 17297475
Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake.
Castro MR, Bergert ER, Goellner JR, Hay ID, Morris JC.
J Clin Endocrinol Metab. 2001 Nov;86(11):5627-32.
PMID 11701745
Early cellular abnormalities induced by RET/PTC1 oncogene in thyroid-targeted transgenic mice.
Cho JY, Sagartz JE, Capen CC, Mazzaferri EL, Jhiang SM.
Oncogene. 1999 Jun 17;18(24):3659-65.
PMID 10380889
Cloning and characterization of the thyroid iodide transporter.
Dai G, Levy O, Carrasco N.
Nature. 1996 Feb 1;379(6564):458-60.
PMID 8559252
Predominant intracellular overexpression of the Na+/I- symporter (NIS) in a large sampling of thyroid cancer cases.
Dohan O, Baloch Z, Banrevi Z, Livolsi V, Carrasco N.
J Clin Endocrinol Metab. 2001 Jun;86(6):2697-700.
PMID 11397873
The sodium/iodide Symporter (NIS): characterization, regulation and medical significance.
Dohan O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, Ginter CS, Carrasco N.
Endocr Rev. 2003 Feb;24(1):48-77. (REVIEW)
PMID 12588808
BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism.
Durante C, Puxeddu E, Ferretti E, Morisi R, Moretti S, Bruno R, Barbi F, Avenia N, Scipioni A, Verrienti A, Tosi E, Cavaliere A, Gulino A, Filetti S, Russo D.
J Clin Endocrinol Metab. 2007 Jul;92(7):2840-3.
PMID 17488796
A preclinical large animal model of adenovirus-mediated expression of the sodium-iodide symporter for radioiodide imaging and therapy of locally recurrent prostate cancer.
Dwyer RM, Schatz SM, Bergert ER, Myers RM, Harvey ME, Classic KL, Blanco MC, Frisk CS, Marler RJ, Davis BJ, O'Connor MK, Russell SJ, Morris JC.
Mol Ther. 2005 Nov;12(5):835-41.
PMID 16054438
Immunohistochemical expression of the human sodium/iodide symporter distinguishes malignant from benign gastric lesions.
Farnedi A, Eusebi LH, Poli F, Foschini MP.
Int J Surg Pathol. 2009 Aug;17(4):327-34.
PMID 19124451
Identification of cyclic adenosine 3',5'-monophosphate response element modulator as an activator of the human sodium/iodide symporter upstream enhancer.
Fenton MS, Marion KM, Hershman JM.
Endocrinology. 2008 May;149(5):2592-606.
PMID 18202121
Valproic acid induces the expression of the Na+/I- symporter and iodine uptake in poorly differentiated thyroid cancer cells.
Fortunati N, Catalano MG, Arena K, Brignardello E, Piovesan A, Boccuzzi G.
J Clin Endocrinol Metab. 2004 Feb;89(2):1006-9.
PMID 14764827
RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase.
Knauf JA, Kuroda H, Basu S, Fagin JA.
Oncogene. 2003 Jul 10;22(28):4406-12.
PMID 12853977
Differential regulation of the human sodium/iodide symporter gene promoter in papillary thyroid carcinoma cell lines and normal thyroid cells.
Kogai T, Hershman JM, Motomura K, Endo T, Onaya T, Brent GA.
Endocrinology. 2001 Aug;142(8):3369-79.
PMID 11459780
Reverse transcriptase inhibitors down-regulate cell proliferation in vitro and in vivo and restore thyrotropin signaling and iodine uptake in human thyroid anaplastic carcinoma.
Landriscina M, Fabiano A, Altamura S, Bagala C, Piscazzi A, Cassano A, Spadafora C, Giorgino F, Barone C, Cignarelli M.
J Clin Endocrinol Metab. 2005 Oct;90(10):5663-71.
PMID 16030158
Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes.
Lazar V, Bidart JM, Caillou B, Mahe C, Lacroix L, Filetti S, Schlumberger M.
J Clin Endocrinol Metab. 1999 Sep;84(9):3228-34.
PMID 10487692
A novel loss-of-function deletion in sodium/iodide symporter gene in follicular thyroid adenoma.
Liang JA, Chen CP, Huang SJ, Ho TY, Hsiang CY, Ding HJ, Wu SL.
Cancer Lett. 2005 Dec 8;230(1):65-71.
PMID 16253762
Sodium iodide symporter is expressed at the preneoplastic stages of liver carcinogenesis and in human cholangiocarcinoma.
Liu B, Herve J, Bioulac-Sage P, Valogne Y, Roux J, Yilmaz F, Boisgard R, Guettier C, Cales P, Tavitian B, Samuel D, Clerc J, Brechot C, Faivre J.
Gastroenterology. 2007 Apr;132(4):1495-503.
PMID 17408651
Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours.
Luciani P, Buci L, Conforti B, Tonacchera M, Agretti P, Elisei R, Vivaldi A, Cioppi F, Biliotti G, Manca G, Vitti P, Serio M, Peri A.
Eur J Endocrinol. 2003 May;148(5):579-86.
PMID 12720543
Correlation between 99mTc-pertechnetate uptakes and expressions of human sodium iodide symporter gene in breast tumor tissues.
Moon DH, Lee SJ, Park KY, Park KK, Ahn SH, Pai MS, Chang H, Lee HK, Ahn IM.
Nucl Med Biol. 2001 Oct;28(7):829-34.
PMID 11578905
The paired-domain transcription factor Pax8 binds to the upstream enhancer of the rat sodium/iodide symporter gene and participates in both thyroid-specific and cyclic-AMP-dependent transcription.
Ohno M, Zannini M, Levy O, Carrasco N, di Lauro R.
Mol Cell Biol. 1999 Mar;19(3):2051-60.
PMID 10022892
Immunoanalysis indicates that the sodium iodide symporter is not overexpressed in intracellular compartments in thyroid and breast cancers.
Peyrottes I, Navarro V, Ondo-Mendez A, Marcellin D, Bellanger L, Marsault R, Lindenthal S, Ettore F, Darcourt J, Pourcher T.
Eur J Endocrinol. 2009 Feb;160(2):215-25.
PMID 19029227
Breast cancer brain metastases express the sodium iodide symporter.
Renier C, Vogel H, Offor O, Yao C, Wapnir I.
J Neurooncol. 2009 Jul 19.
PMID 19618116
Endogenous NIS expression in triple-negative breast cancers.
Renier C, Yao C, Goris M, Ghosh M, Katznelson L, Nowles K, Gambhir SS, Wapnir I.
Ann Surg Oncol. 2009 Apr;16(4):962-8.
PMID 19184238
A perspective view of sodium iodide symporter research and its clinical implications.
Riesco-Eizaguirre G, Santisteban P.
Eur J Endocrinol. 2006 Oct;155(4):495-512. (REVIEW)
PMID 16990649
BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer.
Romei C, Ciampi R, Faviana P, Agate L, Molinaro E, Bottici V, Basolo F, Miccoli P, Pacini F, Pinchera A, Elisei R.
Endocr Relat Cancer. 2008 Jun;15(2):511-20.
PMID 18509003
Promoter characterization of the human Na+/I- symporter.
Ryu KY, Tong Q, Jhiang SM.
J Clin Endocrinol Metab. 1998 Sep;83(9):3247-51.
PMID 9745437
Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer.
Saez C, Martinez-Brocca MA, Castilla C, Soto A, Navarro E, Tortolero M, Pintor-Toro JA, Japon MA.
J Clin Endocrinol Metab. 2006 Apr;91(4):1404-9. Epub 2006 Jan 17.
PMID 16418208
Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas.
Saito T, Endo T, Kawaguchi A, Ikeda M, Katoh R, Kawaoi A, Muramatsu A, Onaya T.
J Clin Invest. 1998 Apr 1;101(7):1296-300.
PMID 9525971
Retinoic acid increases sodium/iodide symporter mRNA levels in human thyroid cancer cell lines and suppresses expression of functional symporter in nontransformed FRTL-5 rat thyroid cells.
Schmutzler C, Winzer R, Meissner-Weigl J, Kohrle J.
Biochem Biophys Res Commun. 1997 Nov 26;240(3):832-8.
PMID 9398654
Cloning of the human sodium lodide symporter.
Smanik PA, Liu Q, Furminger TL, Ryu K, Xing S, Mazzaferri EL, Jhiang SM.
Biochem Biophys Res Commun. 1996 Sep 13;226(2):339-45.
PMID 8806637
Expression, exon-intron organization and chromosome mapping of the human sodium iodide symporter.
Smanik PA, Ryu KY, Theil KS, Mazzaferri EL, Jhiang SM.
Endocrinology. 1997 Aug;138(8):3555-8.
PMID 9231811
The sodium iodide symporter: its pathophysiological and therapeutic implications.
Spitzweg C, Morris JC.
Clin Endocrinol (Oxf). 2002 Nov;57(5):559-74. (REVIEW)
PMID 12390328
A thyroid-specific far-upstream enhancer in the human sodium/iodide symporter gene requires Pax-8 binding and cyclic adenosine 3',5'-monophosphate response element-like sequence binding proteins for full activity and is differentially regulated in normal and thyroid cancer cells.
Taki K, Kogai T, Kanamoto Y, Hershman JM, Brent GA.
Mol Endocrinol. 2002 Oct;16(10):2266-82.
PMID 12351692
The mammary gland iodide transporter is expressed during lactation and in breast cancer.
Tazebay UH, Wapnir IL, Levy O, Dohan O, Zuckier LS, Zhao QH, Deng HF, Amenta PS, Fineberg S, Pestell RG, Carrasco N.
Nat Med. 2000 Aug;6(8):871-8.
PMID 10932223
Benign nonfunctioning thyroid adenomas are characterized by a defective targeting to cell membrane or a reduced expression of the sodium iodide symporter protein.
Tonacchera M, Viacava P, Agretti P, de Marco G, Perri A, di Cosmo C, de Servi M, Miccoli P, Lippi F, Naccarato AG, Pinchera A, Chiovato L, Vitti P.
J Clin Endocrinol Metab. 2002 Jan;87(1):352-7.
PMID 11788674
Evidence for transcriptional and posttranscriptional alterations of the sodium/iodide symporter expression in hypofunctioning benign and malignant thyroid tumors.
Trouttet-Masson S, Selmi-Ruby S, Bernier-Valentin F, Porra V, Berger-Dutrieux N, Decaussin M, Peix JL, Perrin A, Bournaud C, Orgiazzi J, Borson-Chazot F, Franc B, Rousset B.
Am J Pathol. 2004 Jul;165(1):25-34.
PMID 15215159
Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to human Na+/I-symporter gene methylation status.
Venkataraman GM, Yatin M, Marcinek R, Ain KB.
J Clin Endocrinol Metab. 1999 Jul;84(7):2449-57.
PMID 10404820
The Na+/I- symporter mediates iodide uptake in breast cancer metastases and can be selectively down-regulated in the thyroid.
Wapnir IL, Goris M, Yudd A, Dohan O, Adelman D, Nowels K, Carrasco N.
Clin Cancer Res. 2004 Jul 1;10(13):4294-302.
PMID 15240514
Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast and other carcinomas using high density tissue microarrays and conventional sections.
Wapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, Greco RS, Dohan O, Carrasco N.
J Clin Endocrinol Metab. 2003 Apr;88(4):1880-8.
PMID 12679487
Low expression of sodium iodide symporter identifies aggressive thyroid tumors.
Ward LS, Santarosa PL, Granja F, da Assumpcao LV, Savoldi M, Goldman GH.
Cancer Lett. 2003 Oct 8;200(1):85-91.
PMID 14550956
Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor.
Zarnegar R, Brunaud L, Kanauchi H, Wong M, Fung M, Ginzinger D, Duh QY, Clark OH.
Surgery. 2002 Dec;132(6):984-90.
PMID 12490845


This paper should be referenced as such :
Di, Bernardo J ; Rhoden, KJ
SLC5A5 (solute carrier family 5 (sodium iodide symporter), member 5)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(6):581-587.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)SLC5A5   11040
Entrez_Gene (NCBI)SLC5A5    solute carrier family 5 member 5
AliasesNIS; TDH1
GeneCards (Weizmann)SLC5A5
Ensembl hg19 (Hinxton)ENSG00000105641 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000105641 [Gene_View]  ENSG00000105641 [Sequence]  chr19:17871945-17895174 [Contig_View]  SLC5A5 [Vega]
ICGC DataPortalENSG00000105641
TCGA cBioPortalSLC5A5
AceView (NCBI)SLC5A5
Genatlas (Paris)SLC5A5
SOURCE (Princeton)SLC5A5
Genetics Home Reference (NIH)SLC5A5
Genomic and cartography
GoldenPath hg38 (UCSC)SLC5A5  -     chr19:17871945-17895174 +  19p13.11   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SLC5A5  -     19p13.11   [Description]    (hg19-Feb_2009)
GoldenPathSLC5A5 - 19p13.11 [CytoView hg19]  SLC5A5 - 19p13.11 [CytoView hg38]
genome Data Viewer NCBISLC5A5 [Mapview hg19]  
OMIM274400   601843   
Gene and transcription
Genbank (Entrez)AF260700 BC105047 BC105049 BX648217 D87920
RefSeq transcript (Entrez)NM_000453
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SLC5A5
Alternative Splicing GalleryENSG00000105641
Gene ExpressionSLC5A5 [ NCBI-GEO ]   SLC5A5 [ EBI - ARRAY_EXPRESS ]   SLC5A5 [ SEEK ]   SLC5A5 [ MEM ]
Gene Expression Viewer (FireBrowse)SLC5A5 [ Firebrowse - Broad ]
GenevisibleExpression of SLC5A5 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6528
GTEX Portal (Tissue expression)SLC5A5
Human Protein AtlasENSG00000105641-SLC5A5 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ92911   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ92911  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ92911
Splice isoforms : SwissVarQ92911
Domaine pattern : Prosite (Expaxy)NA_SOLUT_SYMP_1 (PS00456)    NA_SOLUT_SYMP_3 (PS50283)   
Domains : Interpro (EBI)Na/Glc_symporter_sf    Na/solute_symporter    Na/solute_symporter_CS    SLC5A5   
Domain families : Pfam (Sanger)SSF (PF00474)   
Domain families : Pfam (NCBI)pfam00474   
Conserved Domain (NCBI)SLC5A5
Blocks (Seattle)SLC5A5
Human Protein Atlas [tissue]ENSG00000105641-SLC5A5 [tissue]
Peptide AtlasQ92911
Protein Interaction databases
IntAct (EBI)Q92911
Ontologies - Pathways
Ontology : AmiGOnucleus  plasma membrane  plasma membrane  plasma membrane  plasma membrane  thyroid hormone generation  ion transport  sodium ion transport  sodium:iodide symporter activity  sodium:iodide symporter activity  iodide transmembrane transporter activity  iodide transmembrane transporter activity  iodide transmembrane transporter activity  iodide transmembrane transporter activity  iodide transmembrane transporter activity  symporter activity  iodide transport  integral component of membrane  extracellular exosome  cellular response to cAMP  cellular response to gonadotropin stimulus  extracellular vesicle  iodide transmembrane transport  iodide transmembrane transport  iodide transmembrane transport  iodide transmembrane transport  
Ontology : EGO-EBInucleus  plasma membrane  plasma membrane  plasma membrane  plasma membrane  thyroid hormone generation  ion transport  sodium ion transport  sodium:iodide symporter activity  sodium:iodide symporter activity  iodide transmembrane transporter activity  iodide transmembrane transporter activity  iodide transmembrane transporter activity  iodide transmembrane transporter activity  iodide transmembrane transporter activity  symporter activity  iodide transport  integral component of membrane  extracellular exosome  cellular response to cAMP  cellular response to gonadotropin stimulus  extracellular vesicle  iodide transmembrane transport  iodide transmembrane transport  iodide transmembrane transport  iodide transmembrane transport  
Pathways : KEGGThyroid hormone synthesis   
REACTOMEQ92911 [protein]
REACTOME PathwaysR-HSA-5619096 [pathway]   
NDEx NetworkSLC5A5
Atlas of Cancer Signalling NetworkSLC5A5
Wikipedia pathwaysSLC5A5
Orthology - Evolution
GeneTree (enSembl)ENSG00000105641
Phylogenetic Trees/Animal Genes : TreeFamSLC5A5
Homologs : HomoloGeneSLC5A5
Homology/Alignments : Family Browser (UCSC)SLC5A5
Gene fusions - Rearrangements
Fusion : Fusion_HubSLC5A5--CENPL    SLC5A5--KIAA0319L    SLC5A5--SMR3B    SYAP1--SLC5A5   
Fusion : QuiverSLC5A5
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSLC5A5 [hg38]
Exome Variant ServerSLC5A5
GNOMAD BrowserENSG00000105641
Varsome BrowserSLC5A5
Genomic Variants (DGV)SLC5A5 [DGVbeta]
DECIPHERSLC5A5 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSLC5A5 
ICGC Data PortalSLC5A5 
TCGA Data PortalSLC5A5 
Broad Tumor PortalSLC5A5
OASIS PortalSLC5A5 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSLC5A5  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSLC5A5
Mutations and Diseases : HGMDSLC5A5
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SLC5A5
DgiDB (Drug Gene Interaction Database)SLC5A5
DoCM (Curated mutations)SLC5A5 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SLC5A5 (select a term)
NCG6 (London) select SLC5A5
Cancer3DSLC5A5(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM274400    601843   
Genetic Testing Registry SLC5A5
NextProtQ92911 [Medical]
Target ValidationSLC5A5
Huge Navigator SLC5A5 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA35905
Clinical trialSLC5A5
canSAR (ICR)SLC5A5 (select the gene name)
DataMed IndexSLC5A5
PubMed158 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Feb 19 18:00:25 CET 2021

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