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SCD (stearoyl-CoA desaturase (delta-9-desaturase))

Written2015-01Amir Mehdizadeh, Shabnam Fayezi, Masoud Darabi
Liver, Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, (AM, MD); Students Research Committee, Department of Anatomy, Cell Biology, Shahid Beheshti University of Medical Sciences School of Medicine, Tehran (SF), Iran;;;

Abstract Despite the presence of monounsaturated fatty acids (MUFA) in the usual diet, these fatty acids may also be synthesized de novo from saturated fatty acids (SFA) through enzymatic desaturase activity (Arregui et al., 2012). Stearoyl-CoA desaturase (SCD)1 and SCD5 isozymes have been identified in human. SCD1 or ?9 desaturase is predominantly expressed in adipose tissue, meibomian, harderian and preputial glands. This enzyme is highly induced in response to high carbohydrate diet (Mauvoisin & Mounier, 2011). It has been proven that the elevated levels of SCD1 are associated with obesity, metabolic disorders and malignancies. Altogether, these findings propose SCD1 as a new therapeutic target.

Keywords Stearoyl-CoA desaturase 1, monounsaturated fatty acids, saturated fatty acids

(Note : for Links provided by Atlas : click)


Alias (NCBI)PRO1933
HGNC Alias symbFADS5
HGNC Alias nameacyl-CoA desaturase
 fatty acid desaturase
HGNC Previous nameSCDOS
HGNC Previous namestearoyl-CoA desaturase opposite strand
 stearoyl-CoA desaturase (delta-9-desaturase)
LocusID (NCBI) 6319
Atlas_Id 43887
Location 10q24.31  [Link to chromosome band 10q24]
Location_base_pair Starts at 100347233 and ends at 100364826 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping SCD.png]
Local_order Locus tag (NCBI), PRO1933. 5'- 100347015 - 100364831 -3'; strand: (-). The human SCD1 gene is centromeric to LINC00263 (long intergenic non-protein coding RNA 263) and telomeric to PKD2L1 (polycystic kidney disease 2-like 1).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
GABRG2 (5q34)::SCD (10q24.31)MGA (15q15.1)::SCD (10q24.31)NAA20 (20p11.23)::SCD (10q24.31)
SCD (10q24.31)::GPR19 (12p13.1)SCD (10q24.31)::SCD (10q24.31)SCD (10q24.31)::SLC25A26 (3p14.1)
TUBB (6p21.33)::SCD (10q24.31)


Note SCD1 gene encodes an enzyme that serves as a fatty acid synthesizing enzyme and mostly produces oleic acid from stearic acid. Transcripts with alternative polyadenlyation and sizes 3.9 and 5.2 kb has been detected for this gene.
  Schematic representation of the genomic organization of exons of the SCD1 gene (17817 bp).
Description SCD1 gene is located on chromosome 10q24.31, spans approximately 24 kb and has 6 exons and is mostly expressed in white adipose tissue and the liver (Arregui et al., 2012). The exon 1 is only 324bp while the exon 6 encodes for around 2 kb 3'-untranslated region (Mauvoisin & Mounier, 2011).
Transcription The critical region for promoter activity is located between nucleotides 496-609 upstream of the translation start site. CCAAT box is identified as an important cis-element binding site in this region (Zhang, Ge, Tran, Stenn, & Prouty, 2001). Different transcription factors such as SREBP-1c, LXR, PPAR-a, C/EBP-a, NF-1, NF-Y, AP-1, Sp1, TR and PGC1-a bind to SCD1 promoter controlling the expression level of SCD1 (Mauvoisin & Mounier, 2011).
Pseudogene Pseudogene of this gene is located on chromosome 17 at 17p11.2. The SCD1 pseudogene has two premature in-frame stop codons and is transcriptionally inactive (Zhang, Ge, Parimoo, Stenn, & Prouty, 1999).


Note SCD1 is an iron containing enzyme which catalyses the oxidation of palmitoyl-CoA and stearoyl-CoA in ?9 position to produce corresponding derivatives palmitoleoyl-CoA and oleoyl-CoA, respectively. Formation of cis double bond is mediated by electeron-transfer proteins sequentially NADH-cytochrome b5 reductase, cytochrome b5 and SCD. Electrons flow from NADPH source to cytochrome b5 reductase and to the cytochrome b5 as the direct electron donor to SCD1 and finally to O2 which is reduced to H2O. The rate-limiting step in this reaction is desaturase (Zhang et al., 1999).
  A schematic representation of the domain structure of SCD1 protein (359 amino acids total), which consists of cytoplasmic, transmembrane, and lumenal domains.
Description SCD1 contains four transmembrane domain which two NH2 and COOH terminals are located in cytoplasmic side. The single cytoplasmic loop and COOH terminus collectively contain eight Histidine residues forming His box and bind to iron at the center of catalytic site of desaturase. Two ER luminal loops are relatively smaller than cytosolic loop which contain two of the three conserved His motifs. Purified SCD1 remains in 37kDa band on SDS-PAGE and His segments located in 119, 156 and 296 provide ligands for nonheme iron within the catalytic site of the SCD1 (Paton & Ntambi, 2009).
Expression SCD1 promoter contains several transcription factor binding sites that are involved in positive or negative regulation of SCD1 gene. Sterol regulatory element-binding proteins (SREBP) are a group of transcriptional factors belonging to helix-loop-helix leucine zipper family and are responsible for regulating cholesterol, fatty acids and triglyceride synthesis enzymes (Miyazaki et al., 2004). SREBP-1a is the dominant isoform of SREBP in human cultured cells and induces SCD1 gene expression (Shimomura, Shimano, Horton, Goldstein, & Brown, 1997). Furthermore, Liver X Receptors (LXR) including LXR-? and LXR-? serve as positive inducers of SCD1 gene (Peter et al., 2008). Therefore, PPAR? in combination with LXR causes elevation in the levels of SCD1 gene expression (Hebbachi, Knight, Wiggins, Patel, & Gibbons, 2008). The involvement of PPAR? in transcriptional regulation of SCD1 has also been reported in human pancreatic cells. Specifically, MEK/ERK1/2- and EGFR-dependent pathways exerted inhibitory effect on the expression and activity of SCD1 in these cells, possibly via PPAR? activation (Byagowi et al. 2015).
Localisation SCD1 is anchored to reticulum endoplasmic membrane (Liu, Strable, & Ntambi, 2011).
Function SCD1 is a rate-limiting enzyme which converts SFA to MUFA mainly oleate and palmitate causing high contents of MUFA in membrane phospholipids, triclycerides and cholesterol esters (Matsui et al., 2012).
Homology Two SCD isoforms, SCD1 and SCD5 have been identified in human. SCD1 has a high degree of homology with SCD5 in human genome. Four SCD isoforms, SCD1 to SCD4 have also been identified in mouse. SCD1 shares about 85% amino acid identity with all 4 mouse SCD isoforms, as well as with rat SCD1 and SCD2. In contrast, SCD5 shares limited homology with the rodent SCDs and appears to be unique to primates (Wang et al., 2005). [supplied by OMIM, Mar 2008]. (Leung & Kim, 2013).


Note SCD1 gene is located on 10q24.31 position and shows different sequence polymorphisms (SNPs). Among these polymorphisms, rs3071, rs1502593 and rs10883463 SNPs have a higher degree of mean allele frequency (MAF) and are more studied. These SNPs has been implicated in multiple aspects of lipid metabolism. Also, rare alleles of rs10883463, rs7849, rs2167444, and rs508384 are associated with decreased BMI and improved insulin sensitivity (Abdelmagid et al., 2013; Arregui et al., 2012; Gong et al., 2011).

Implicated in

Entity Breast cancer
Note Over-expression of SCD1 is associated with enhanced growth rate of breast cancer cell lines and shorter overall survival and relapse-free survival (RFS) in breast cancer patients (Holder et al., 2013). Furthermore, it is demonstrated that high desaturation index has a negative correlation with the risk of breast cancer (Chajs et al., 1999). Down-regulation of SCD1 by specific siRNA also leads to reduction of proliferation rate, cell cycles' gene expression and phosphorylation state of ERK1/2 (Mauvoisin, Charfi, Lounis, Rassart, & Mounier, 2013). On the other hand, Mohammadzadeh et al. study revealed that inhibition of SCD1 by a selective inhibitor causes significant alteration in fatty acid composition of tissue cultured breast carcinoma in comparison to normal-appearing breast tissues and this has been attributed to the different level of SCD1 activity (Mohammadzadeh et al., 2014).
Entity Hepatocellular carcinoma
Note Bansal et al. study indicated that SCD1 was significantly over-expressed in hepatocellular carcinoma (HCC) tissues in comparison to adjacent normal tissues and in HCC cell lines including HepG2, Hep3B and PLC/PLF/5. Furthermore, the level of SCD1 was negatively associated with tumour differentiation grade. Treatment of liver cancer cell lines with different panel of chemotherapeutic agents also caused over expression of SCD1 in a time dependent manner and the consequent resistance to drug induced apoptosis. It is also demonstrated that inhibition of SCD1 by genetic manipulation or chemical inhibitors leads to elevated sensitivity to chemotherapeutic agents (Bansal et al., 2013).
Entity Colorectal cancer
Note Recent studies have revealed that cell death is induced in colorectal cancer cells following SCD1 inhibition. This effect is most possibly mediated through caspase 3 activity and PPAR-cleavage (Minville-Walz et al., 2010). Other studies have also reported that HTC116 colon cancer cell lines are susceptible to SCD1 depletion and subsequent decreased cell viability (Mason et al., 2012).
Entity Esophageal cancer
Note Shuai Guo et al. study has shown SCD1 up-regulation in esophageal cancerous tissues in comparison to adjacent normal tissues. Furthermore, tissue lipid distribution analysis revealed that MUFA/PUFA ratio is elevated in cancerous microenvironment due to over activation of SCD1 (Guo, Wang, Zhou, & Li, 2014).
Entity Gastric cancer
Note Roongta et al. reported SCD1 inhibition causes tumour growth delay in a xenograft model in nude mice (Roongta et al., 2011).
Entity Obesity
Note Obesity and type 2 diabetes are highly associated with abnormal lipid metabolism and intramyocellular accumulation of triglycerides. Hulver et al reported that SCD1 is up-regulated in skeletal myocytes of obese individuals. Overexpression and overactivity of SCD1 is linked to lower fatty acid ?-oxidation rate and elevation of triglyceride and MUFA synthesis in extremely obese population (Hulver et al., 2005).
Entity Lipotoxicity and inflammation
Note Lipotoxicity is a common characteristic of diabetes and metabolic syndrome. It is defined by the elevation of intracellular fatty acid metabolites including diacylglycerol and ceramides leading to endoplasmic reticulum (ER) stress. This cellular stress triggers phosphorylation of insulin receptor substrates in serine/threonine residues and activation of the nuclear factor (NF)-?B pathway (Eizirik, Cardozo, & Cnop, 2008). Such signalling pathways induce an acute inflammatory response with cytokines secretion and diminished down-stream events of insulin receptor signalling cascade resulting in low-grade inflammatory state (Peter et al., 2009). Among SFA, stearate and palmitate have a high lipotoxicity potential to induce inflammation, ER stress and insulin resistance (Staiger et al., 2006). SCD1 enzyme desaturases stearate and palmitate to less toxic monounsaturated forms oleate and palmitoleate (Peter et al., 2008). Overexpression of SCD1 is also associated with increased triglyceride storage and decreased palmitate-induced apoptosis, ceramide and diacylglycerol synthesis, as well as insulin resistance (Pinnamaneni, Southgate, Febbraio, & Watt, 2006).

To be noted

Acknowledgments and support. This research was supported by a grant to Masoud Darabi (research project number, 115/175) from the Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.


Plasma concentration of cis9trans11 CLA in males and females is influenced by SCD1 genetic variations and hormonal contraceptives: a cross-sectional study
Abdelmagid SA, Clarke SE, Wong J, Roke K, Nielsen D, Badawi A, El-Sohemy A, Mutch DM, Ma DW
Nutr Metab (Lond) 2013 Jul 18;10:50
PMID 23866021
Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) gene and metabolic risk factors in the EPIC-Potsdam study
Arregui M, Buijsse B, Stefan N, Corella D, Fisher E, di Giuseppe R, Coltell O, Knüppel S, Aleksandrova K, Joost HG, Boeing H, Weikert C
PLoS One 2012;7(11):e48338
PMID 23139775
Stearoyl-CoA desaturase plays an important role in proliferation and chemoresistance in human hepatocellular carcinoma
Bansal S, Berk M, Alkhouri N, Partrick DA, Fung JJ, Feldstein A
J Surg Res 2014 Jan;186(1):29-38
PMID 24135379
Effect of PPAR Agonist on Stearoyl-CoA Desaturase 1 in Human Pancreatic Cancer Cells: Role of MEK/ERK1/2 Pathway
Byagowi S, Naserpour Farivar T, Najafipour R, Sahmani M, Darabi M, Fayezi S, Mirshahvaladi S, Darabi M
Can J Diabetes 2015 Apr;39(2):123-7
PMID 25575964
Fatty-acid composition in serum phospholipids and risk of breast cancer: an incident case-control study in Sweden
Chajès V, Hultén K, Van Kappel AL, Winkvist A, Kaaks R, Hallmans G, Lenner P, Riboli E
Int J Cancer 1999 Nov 26;83(5):585-90
PMID 10521790
The role for endoplasmic reticulum stress in diabetes mellitus
Eizirik DL, Cardozo AK, Cnop M
Endocr Rev 2008 Feb;29(1):42-61
PMID 18048764
Genetic variation in stearoyl-CoA desaturase 1 is associated with metabolic syndrome prevalence in Costa Rican adults
Gong J, Campos H, McGarvey S, Wu Z, Goldberg R, Baylin A
J Nutr 2011 Dec;141(12):2211-8
PMID 22049297
Significantly increased monounsaturated lipids relative to polyunsaturated lipids in six types of cancer microenvironment are observed by mass spectrometry imaging
Guo S, Wang Y, Zhou D, Li Z
Sci Rep 2014 Aug 5;4:5959
PMID 25091112
Peroxisome proliferator-activated receptor alpha deficiency abolishes the response of lipogenic gene expression to re-feeding: restoration of the normal response by activation of liver X receptor alpha
Hebbachi AM, Knight BL, Wiggins D, Patel DD, Gibbons GF
J Biol Chem 2008 Feb 22;283(8):4866-76
PMID 18079124
High stearoyl-CoA desaturase 1 expression is associated with shorter survival in breast cancer patients
Holder AM, Gonzalez-Angulo AM, Chen H, Akcakanat A, Do KA, Fraser Symmans W, Pusztai L, Hortobagyi GN, Mills GB, Meric-Bernstam F
Breast Cancer Res Treat 2013 Jan;137(1):319-27
PMID 23208590
Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans
Hulver MW, Berggren JR, Carper MJ, Miyazaki M, Ntambi JM, Hoffman EP, Thyfault JP, Stevens R, Dohm GL, Houmard JA, Muoio DM
Cell Metab 2005 Oct;2(4):251-61
PMID 16213227
Stearoyl co-A desaturase 1 as a ccRCC therapeutic target: death by stress
Leung JY, Kim WY
Clin Cancer Res 2013 Jun 15;19(12):3111-3
PMID 23709675
Stearoyl CoA desaturase 1: role in cellular inflammation and stress
Liu X, Strable MS, Ntambi JM
Adv Nutr 2011 Jan;2(1):15-22
PMID 22211186
SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids
Mason P, Liang B, Li L, Fremgen T, Murphy E, Quinn A, Madden SL, Biemann HP, Wang B, Cohen A, Komarnitsky S, Jancsics K, Hirth B, Cooper CG, Lee E, Wilson S, Krumbholz R, Schmid S, Xiang Y, Booker M, Lillie J, Carter K
PLoS One 2012;7(3):e33823
PMID 22457791
Stearoyl-CoA desaturase-1 (SCD1) augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes
Matsui H, Yokoyama T, Sekiguchi K, Iijima D, Sunaga H, Maniwa M, Ueno M, Iso T, Arai M, Kurabayashi M
PLoS One 2012;7(3):e33283
PMID 22413010
Decreasing stearoyl-CoA desaturase-1 expression inhibits -catenin signaling in breast cancer cells
Mauvoisin D, Charfi C, Lounis AM, Rassart E, Mounier C
Cancer Sci 2013 Jan;104(1):36-42
PMID 23013158
Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells
Minville-Walz M, Pierre AS, Pichon L, Bellenger S, Fèvre C, Bellenger J, Tessier C, Narce M, Rialland M
PLoS One 2010 Dec 16;5(12):e14363
PMID 21179554
Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms
Miyazaki M, Dobrzyn A, Man WC, Chu K, Sampath H, Kim HJ, Ntambi JM
J Biol Chem 2004 Jun 11;279(24):25164-71
PMID 15066988
Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition
Mohammadzadeh F, Mosayebi G, Montazeri V, Darabi M, Fayezi S, Shaaker M, Rahmati M, Baradaran B, Mehdizadeh A, Darabi M
J Breast Cancer 2014 Jun;17(2):136-42
PMID 25013434
Biochemical and physiological function of stearoyl-CoA desaturase
Paton CM, Ntambi JM
Am J Physiol Endocrinol Metab 2009 Jul;297(1):E28-37
PMID 19066317
Individual stearoyl-coa desaturase 1 expression modulates endoplasmic reticulum stress and inflammation in human myotubes and is associated with skeletal muscle lipid storage and insulin sensitivity in vivo
Peter A, Weigert C, Staiger H, Machicao F, Schick F, Machann J, Stefan N, Thamer C, Häring HU, Schleicher E
Diabetes 2009 Aug;58(8):1757-65
PMID 19478146
Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro
Pinnamaneni SK, Southgate RJ, Febbraio MA, Watt MJ
Diabetologia 2006 Dec;49(12):3027-37
PMID 17033839
Cancer cell dependence on unsaturated fatty acids implicates stearoyl-CoA desaturase as a target for cancer therapy
Roongta UV, Pabalan JG, Wang X, Ryseck RP, Fargnoli J, Henley BJ, Yang WP, Zhu J, Madireddi MT, Lawrence RM, Wong TW, Rupnow BA
Mol Cancer Res 2011 Nov;9(11):1551-61
PMID 21954435
Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells
Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS
J Clin Invest 1997 Mar 1;99(5):838-45
PMID 9062340
Saturated, but not unsaturated, fatty acids induce apoptosis of human coronary artery endothelial cells via nuclear factor-kappaB activation
Staiger K, Staiger H, Weigert C, Haas C, Häring HU, Kellerer M
Diabetes 2006 Nov;55(11):3121-6
PMID 17065351
Isolation and characterization of the human stearoyl-CoA desaturase gene promoter: requirement of a conserved CCAAT cis-element
Zhang L, Ge L, Tran T, Stenn K, Prouty SM
Biochem J 2001 Jul 1;357(Pt 1):183-93
PMID 11415448


This paper should be referenced as such :
Amir Mehdizadeh, Shabnam Fayezi, Masoud Darabi
SCD (stearoyl-CoA desaturase (delta-9-desaturase))
Atlas Genet Cytogenet Oncol Haematol. 2016;20(2):77-80.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)SCD   10571
Entrez_Gene (NCBI)SCD    stearoyl-CoA desaturase
AliasesFADS5; MSTP008; SCD1; SCDOS; 
GeneCards (Weizmann)SCD
Ensembl hg19 (Hinxton)ENSG00000099194 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000099194 [Gene_View]  ENSG00000099194 [Sequence]  chr10:100347233-100364826 [Contig_View]  SCD [Vega]
ICGC DataPortalENSG00000099194
TCGA cBioPortalSCD
Genatlas (Paris)SCD
SOURCE (Princeton)SCD
Genetics Home Reference (NIH)SCD
Genomic and cartography
GoldenPath hg38 (UCSC)SCD  -     chr10:100347233-100364826 +  10q24.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SCD  -     10q24.31   [Description]    (hg19-Feb_2009)
GoldenPathSCD - 10q24.31 [CytoView hg19]  SCD - 10q24.31 [CytoView hg38]
Genome Data Viewer NCBISCD [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB032261 AB208982 AF097514 AF109362 AI740935
RefSeq transcript (Entrez)NM_005063
Consensus coding sequences : CCDS (NCBI)SCD
Gene ExpressionSCD [ NCBI-GEO ]   SCD [ EBI - ARRAY_EXPRESS ]   SCD [ SEEK ]   SCD [ MEM ]
Gene Expression Viewer (FireBrowse)SCD [ Firebrowse - Broad ]
GenevisibleExpression of SCD in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6319
GTEX Portal (Tissue expression)SCD
Human Protein AtlasENSG00000099194-SCD [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)SCD
Human Protein Atlas [tissue]ENSG00000099194-SCD [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed173 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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