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THRSP (thyroid hormone responsive)

Written2010-09Nancy B Kuemmerle, William B Kinlaw
Dept of Physiology, Dartmouth Medical School - Lebanon, New Hampshire, USA (NBK); Norris Cotton Cancer Center at Dartmouth Medical School - Lebanon, New Hampshire, USA (NBK, WBK); Dept of Medicine, Section of Endocrinology, Metabolism, Dartmouth Medical School - Lebanon, New Hampshire, USA (WBK)

(Note : for Links provided by Atlas : click)


HGNC Alias symbSPOT14
HGNC Alias nameSPOT14 homolog (rat)
HGNC Previous nameLPGP1
HGNC Previous namethyroid hormone responsive SPOT14 (rat) homolog
 lipogenic protein 1
LocusID (NCBI) 7069
Atlas_Id 42555
Location 11q14.1  [Link to chromosome band 11q14]
Location_base_pair Starts at 78063861 and ends at 78068351 bp from pter ( according to hg19-Feb_2009)  [Mapping THRSP.png]
Local_order According to NCBI Map Viewer, genes flanking THRSP in centromere to telomere direction on 11q13 are:
PHCA (11q13.5), phytoceramidase, alkaline;
GDPD4 (11q13.5), glycerophosphate phosphodiesterase domain containing 4;
PAK1 (11q13-14), p21/cdc42/Rac1-activated kinase1 (STE20 homolog, yeast);
DFKZp434E1119 (11q14.1), hypothetical protein DFKZp434e1119;
AQP11 (11q14.1), aquaporin 11;
LOC646195 (11q14.1), ribosomal protein S28 pseudogene;
LOC143543 (11q14.1), RNA binding motif protein X-linked pseudogene;
RAB30 (11q12-q14), RAB30, member RAS oncogene family;
PCF11 (11q13), PCF11, cleavage and polyadenylation factor subunit, homolog (S. cerevisiae).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ACER3 (11q13.5) / THRSP (11q14.1)CACNA2D2 (3p21.31) / THRSP (11q14.1)GAB2 (11q14.1) / THRSP (11q14.1)
PC (11q13.2) / THRSP (11q14.1)THRSP (11q14.1) / KCTD14 (11q14.1)


  An intron (thin line) connects the two exons of THRSP. Most of the 5' exon (thickest line) is translated.
Description According to Entrez-Gene, THRSP maps to NC_000011.9 in the region between 77774907 and 77779307 on the plus strand and spans 5.6 kilobases. According to Spidey (mRNA to genomic sequence alignment tool), THRSP has two exons, the sizes being 481 and 603 bp. Only the smaller of these is translated.
Transcription THRSP mRNA NM_003251.2 has 1084 nt. The coding region of human mRNA for THRSP has 438 nt. Transcription is regulated via thyroid hormone and the SREBP-1c binding sites. Expression can be induced by progestin, glucose, thyroid hormone, and insulin. Antisense RNA knocks down S14 expression in hepatocytes, and this abrogates the induction of genes concerned with fatty acid synthesis by triiodothyronine and glucose.
Pseudogene The ancestral S14-related protein, also known as Strait 11499 and Mig12, may duplicate the function of S14 in hepatic, but not mammary, tissue.


Note THRSP is primarily a nuclear protein which is important in the regulation of lipid metabolism. It is induced by thyroid hormone, carbohydrate intake, adipose tissue differentiation, and lactation, and is inhibited by glucagon and conjugated linoleic acid. Expression of THRSP (Spot14) parallels that of fatty acid synthase in adipose, liver, and mammary tissue in bovine and murine species. Elevated expression of THRSP in human breast tumors is correlated with poor prognosis, whereas absence of expression is associated with longer survival.
Description A driver of de novo saturated fatty acid synthesis in normal and malignant tissues, Spot14 (S14, THRSP) was named for its position on two-dimensional gels of in vitro translation products. The gene is rapidly induced by thyroid hormone in rat liver, and it is strongly activated by glucose metabolism. An acidic protein of approximately 16 kD, it is localized primarily in the nucleus; three domains are conserved from its ancestral protein, Strait1499, also known as Mig12 and S14-related protein.
From immunohistochemical studies, the temporal and spatial expression patterns of murine Spot14 and fatty acid synthase (FASN) were regulated in parallel in mammary epithelium during pregnancy, lactation, and involution. In cattle, milk fat depression is associated with production of conjugated linoleic acid (CLA) isomers as intermediates of fatty acid synthesis by rumen bacteria. Ingestion of a low forage, high oil diet leads to increased production of CLA, and this results in low milk fat content, and decreased expression of S14, FASN, sterol response element binding protein (SREBP), and responsive genes INSIG1 and INSIG2 in a coordinate manner. Breast epithelium does not express detectable levels of Spot14 or FASN in the resting state; however, during pregnancy and lactation, Spot14 and enzymes of lipid biosynthesis are expressed at high levels. Spot14 and FASN are expressed in most breast cancers, and high levels of Spot14 expression portend an aggressive course and high risk of recurrence, regardless of nodal status at diagnosis. Thus Spot14 represents a potential target for therapeutic intervention in cancer.
Expression Spot14 protein is expressed primarily in tissues which synthesize fatty acids. These tissues include white and brown adipose tissue, breast tissue, and liver. Expression is observed in a variety of malignancies, and it is a component of the lipogenic tumor phenotype, e.g., in human breast cancer.
Localisation By immunohistochemistry, Spot14 is localized primarily in the nucleus of rat liver, human mammary gland, and breast cancer cells.
Function Spot14 is involved in the regulation of lipid biosynthesis. Its precise function is not known. It exists as a heterodimer in human cells which are actively synthesizing lipids. Triggers for the induction of Spot14, such as hormones or refeeding after fasting, also trigger FASN activity. Furthermore, siRNAs and anti-sense RNAs directed against Spot14 inhibit expression of genes coding the lipid-synthesizing enzymes.
Homology Homologous proteins are found in cow, rat, mouse, chicken, dog, and chimpanzee, as well as other species. An acidic protein of approximately 16.4 kDa, human THRSP bears 99% homology to its counterpart in Pan troglodytes, 91% to that in Macaca mulatta, 82% to that in Mus musculus, and 80% to that in Rattus norvegicus (data from NCBI BLAST). Three domains are conserved from the ancestral S14-related peptide (Strait 11499, Mig12, S14-related protein).


Note Mutations have been characterized in the chicken. Single-nucleotide polymorphisms (SNPs) have been noted in cow, rat, mouse, and chimpanzee. The SNP database in NCBI lists 63 human SNPs for THRSP.

Implicated in

Entity Breast tumors
Note Along with cyclin D1, which shares the same amplicon at 11q13, S14 is amplified in about 20% of human breast cancers. Although cyclin D1 is a human and murine mammary oncogene, it was the concomitant overexpression of S14 and lipogenic enzymes in aggressive breast tumors that prompted investigation of the role of fatty acid metabolism in metastasis and recurrence of breast tumors. In an immunohistochemical study of invasive breast tumors, high levels of S14 expression correlated with reduced disease-free survival, irrespective of nodal status at diagnosis; there were no recurrences among those whose tumors expressed low levels of S14, even after prolonged follow-up. S14 expression levels did not segregate with cyclin D1, Her-2/neu amplification status, or hormone receptor status. Thus it appears that S14 promotes a virulent, lipogenic phenotype in breast tumors.
Entity Aberrant hepatic lipogenesis and hepatic steatosis
Note The relationship between lipid metabolism and disease is further corroborated by the finding in human hepatocytes that the pregnane X receptor (PXR), which is a nuclear receptor regulating xenobiotic and drug metabolism, upregulates lipogenesis via S14. Stimulation of PXR also enhances expression of the cd36 gene, which permits the uptake of exogenous fatty acids by cells, and also stimulates de novo lipogenesis as well as upregulation of the enzymes involved in lipid synthesis. Knockdown by short interfering RNAs to PXR, S14, or FASN abrogates lipid synthesis. S14-directed fatty acid synthesis has also been implicated in aberrant hepatic lipogenesis and hepatic steatosis.
Entity Obesity
Note It is possible that Spot14 plays a role in the regulation of lipid storage in humans. Whereas nonobese humans downregulate the level of Spot14 in response to fasting, obese subjects do not. Postfasting levels of glucose, insulin, and ketones did not differ between the two groups. The abnormal downregulation of Spot14 in adipose tissue of obese subjects implies that Spot14 may be important to the acquisition or maintenance of obesity in humans.


"Spot 14" protein functions at the pretranslational level in the regulation of hepatic metabolism by thyroid hormone and glucose.
Brown SB, Maloney M, Kinlaw WB.
J Biol Chem. 1997 Jan 24;272(4):2163-6.
PMID 8999918
Spot 14 protein interacts and co-operates with chicken ovalbumin upstream promoter-transcription factor 1 in the transcription of the L-type pyruvate kinase gene through a specificity protein 1 (Sp1) binding site.
Compe E, de Sousa G, Francois K, Roche R, Rahmani R, Torresani J, Raymondjean M, Planells R.
Biochem J. 2001 Aug 15;358(Pt 1):175-83.
PMID 11485565
Amplification of chromosome band 11q13 and a role for cyclin D1 in human breast cancer.
Dickson C, Fantl V, Gillett C, Brookes S, Bartek J, Smith R, Fisher C, Barnes D, Peters G.
Cancer Lett. 1995 Mar 23;90(1):43-50. (REVIEW)
PMID 7720042
SREBP1 and thyroid hormone responsive spot 14 (S14) are involved in the regulation of bovine mammary lipid synthesis during diet-induced milk fat depression and treatment with CLA.
Harvatine KJ, Bauman DE.
J Nutr. 2006 Oct;136(10):2468-74.
PMID 16988111
Direct evidence for a role of the "spot 14" protein in the regulation of lipid synthesis.
Kinlaw WB, Church JL, Harmon J, Mariash CN.
J Biol Chem. 1995 Jul 14;270(28):16615-8.
PMID 7622469
Spot 14: A marker of aggressive breast cancer and a potential therapeutic target.
Kinlaw WB, Quinn JL, Wells WA, Roser-Jones C, Moncur JT.
Endocrinology. 2006 Sep;147(9):4048-55. Epub 2006 Jun 29. (REVIEW)
PMID 16809441
Thyroid hormone and dietary carbohydrate induce different hepatic zonation of both "spot 14" and acetyl-coenzyme-A carboxylase: a novel mechanism of coregulation.
Kinlaw WB, Tron P, Witters LA.
Endocrinology. 1993 Aug;133(2):645-50.
PMID 8102096
Adipose S14 mRNA is abnormally regulated in obese subjects.
Kirschner LS, Mariash CN.
Thyroid. 1999 Feb;9(2):143-8.
PMID 10090313
S14 protein in breast cancer cells: direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth.
Martel PM, Bingham CM, McGraw CJ, Baker CL, Morganelli PM, Meng ML, Armstrong JM, Moncur JT, Kinlaw WB.
Exp Cell Res. 2006 Feb 1;312(3):278-88. Epub 2005 Nov 21.
PMID 16300755
Sterol response element-binding protein 1c (SREBP1c) is involved in the polyunsaturated fatty acid suppression of hepatic S14 gene transcription.
Mater MK, Thelen AP, Pan DA, Jump DB.
J Biol Chem. 1999 Nov 12;274(46):32725-32.
PMID 10551830
Assignment of the "spot 14" gene (THRSP) to human chromosome band 11q13.5 by in situ hybridization.
Moncur JT, Park JP, Maloney M, Mohandas TK, Kinlaw WB.
Cytogenet Cell Genet. 1997;78(2):131-2.
PMID 9371405
A novel pregnane X receptor and S14-mediated lipogenic pathway in human hepatocyte.
Moreau A, Teruel C, Beylot M, Albalea V, Tamasi V, Umbdenstock T, Parmentier Y, Sa-Cunha A, Suc B, Fabre JM, Navarro F, Ramos J, Meyer U, Maurel P, Vilarem MJ, Pascussi JM.
Hepatology. 2009 Jun;49(6):2068-79.
PMID 19437491
Thyroid hormone attenuates and augments hepatic gene expression at a pretranslational level.
Seelig S, Liaw C, Towle HC, Oppenheimer JH.
Proc Natl Acad Sci U S A. 1981 Aug;78(8):4733-7.
PMID 6946422
Hepatic expression of the SPOT 14 (S14) paralog S14-related (Mid1 interacting protein) is regulated by dietary carbohydrate.
Tsatsos NG, Augustin LB, Anderson GW, Towle HC, Mariash CN.
Endocrinology. 2008 Oct;149(10):5155-61. Epub 2008 Jun 12.
PMID 18556348
Duplicated Spot 14 genes in the chicken: characterization and identification of polymorphisms associated with abdominal fat traits.
Wang X, Carre W, Zhou H, Lamont SJ, Cogburn LA.
Gene. 2004 May 12;332:79-88.
PMID 15145057
Expression of "Spot 14" (THRSP) predicts disease free survival in invasive breast cancer: immunohistochemical analysis of a new molecular marker.
Wells WA, Schwartz GN, Morganelli PM, Cole BF, Gibson JJ, Kinlaw WB.
Breast Cancer Res Treat. 2006 Jul;98(2):231-40. Epub 2006 Mar 22.
PMID 16552628
Activation of fatty acid synthesis during neoplastic transformation: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase.
Yang YA, Han WF, Morin PJ, Chrest FJ, Pizer ES.
Exp Cell Res. 2002 Sep 10;279(1):80-90.
PMID 12213216


This paper should be referenced as such :
Kuemmerle, NB ; Kinlaw, WB
THRSP (thyroid hormone responsive)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(6):480-482.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 5 ]
  t(3;11)(p21;q14) CACNA2D2/THRSP
t(11;11)(q13;q14) ACER3/THRSP
t(11;11)(q13;q14) PC/THRSP
GAB2/THRSP (11q14)
THRSP/KCTD14 (11q14)

External links

HGNC (Hugo)THRSP   11800
Entrez_Gene (NCBI)THRSP  7069  thyroid hormone responsive
AliasesLPGP1; Lpgp; S14; SPOT14; 
GeneCards (Weizmann)THRSP
Ensembl hg19 (Hinxton)ENSG00000151365 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000151365 [Gene_View]  ENSG00000151365 [Sequence]  chr11:78063861-78068351 [Contig_View]  THRSP [Vega]
ICGC DataPortalENSG00000151365
Genatlas (Paris)THRSP
Genetics Home Reference (NIH)THRSP
Genomic and cartography
GoldenPath hg38 (UCSC)THRSP  -     chr11:78063861-78068351 +  11q14.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)THRSP  -     11q14.1   [Description]    (hg19-Feb_2009)
GoldenPathTHRSP - 11q14.1 [CytoView hg19]  THRSP - 11q14.1 [CytoView hg38]
genome Data Viewer NCBITHRSP [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AI480357 AI749106 AK311975 BC031989 BG674197
RefSeq transcript (Entrez)NM_003251
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)THRSP
Alternative Splicing GalleryENSG00000151365
Gene Expression Viewer (FireBrowse)THRSP [ Firebrowse - Broad ]
GenevisibleExpression of THRSP in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7069
GTEX Portal (Tissue expression)THRSP
Human Protein AtlasENSG00000151365-THRSP [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ92748   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ92748  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ92748
Splice isoforms : SwissVarQ92748
Domains : Interpro (EBI)Spot_14   
Domain families : Pfam (Sanger)Spot_14 (PF07084)   
Domain families : Pfam (NCBI)pfam07084   
Conserved Domain (NCBI)THRSP
DMDM Disease mutations7069
Blocks (Seattle)THRSP
Human Protein Atlas [tissue]ENSG00000151365-THRSP [tissue]
Peptide AtlasQ92748
Protein Interaction databases
IntAct (EBI)Q92748
Ontologies - Pathways
Ontology : AmiGOnucleoplasm  cytosol  cytosol  cytosol  lipid metabolic process  carnitine shuttle  response to bacterium  regulation of triglyceride biosynthetic process  identical protein binding  protein homodimerization activity  regulation of lipid biosynthetic process  regulation of lipid biosynthetic process  
Ontology : EGO-EBInucleoplasm  cytosol  cytosol  cytosol  lipid metabolic process  carnitine shuttle  response to bacterium  regulation of triglyceride biosynthetic process  identical protein binding  protein homodimerization activity  regulation of lipid biosynthetic process  regulation of lipid biosynthetic process  
REACTOMEQ92748 [protein]
REACTOME PathwaysR-HSA-200425 [pathway]   
Atlas of Cancer Signalling NetworkTHRSP
Wikipedia pathwaysTHRSP
Orthology - Evolution
GeneTree (enSembl)ENSG00000151365
Phylogenetic Trees/Animal Genes : TreeFamTHRSP
Homologs : HomoloGeneTHRSP
Homology/Alignments : Family Browser (UCSC)THRSP
Gene fusions - Rearrangements
Fusion : MitelmanACER3/THRSP [11q13.5/11q14.1]  
Fusion : MitelmanCACNA2D2/THRSP [3p21.31/11q14.1]  
Fusion : MitelmanGAB2/THRSP [11q14.1/11q14.1]  
Fusion : MitelmanPC/THRSP [11q13.2/11q14.1]  
Fusion : MitelmanTHRSP/KCTD14 [11q14.1/11q14.1]  
Fusion PortalACER3 11q13.5 THRSP 11q14.1 BRCA
Fusion PortalCACNA2D2 3p21.31 THRSP 11q14.1 SKCM
Fusion PortalGAB2 11q14.1 THRSP 11q14.1 BRCA
Fusion PortalPC 11q13.2 THRSP 11q14.1 BRCA
Fusion PortalTHRSP 11q14.1 KCTD14 11q14.1 BRCA
Fusion : QuiverTHRSP
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTHRSP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)THRSP
Exome Variant ServerTHRSP
GNOMAD BrowserENSG00000151365
Varsome BrowserTHRSP
Genetic variants : HAPMAP7069
Genomic Variants (DGV)THRSP [DGVbeta]
DECIPHERTHRSP [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTHRSP 
ICGC Data PortalTHRSP 
TCGA Data PortalTHRSP 
Broad Tumor PortalTHRSP
OASIS PortalTHRSP [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTHRSP  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DTHRSP
Mutations and Diseases : HGMDTHRSP
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 THRSP
DgiDB (Drug Gene Interaction Database)THRSP
DoCM (Curated mutations)THRSP (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)THRSP (select a term)
NCG6 (London) select THRSP
Cancer3DTHRSP(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry THRSP
NextProtQ92748 [Medical]
Target ValidationTHRSP
Huge Navigator THRSP [HugePedia]
snp3D : Map Gene to Disease7069
Clinical trials, drugs, therapy
Protein Interactions : CTD7069
Pharm GKB GenePA36509
Clinical trialTHRSP
canSAR (ICR)THRSP (select the gene name)
DataMed IndexTHRSP
PubMed27 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 : Thu Jul 16 16:54:47 CEST 2020

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