1. Gene Aliases

SCD, FADS5, SCD1, Fatty Acid Desaturase, Acyl-CoA Desaturase, SCDOS, Stearoyl-CoA Desaturase (Delta-9-Desaturase), Stearoyl-CoA Desaturase Opposite Strand, Delta(9)-Desaturase, EC 1.14.19.1, HSCD1, Predicted Protein Of HQ0998, Delta-9-Desaturase, Delta-9 Desaturase, MSTP008

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=SCD&keywords=scd]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

brown fat cell differentiation [The process in which a relatively unspecialized cell acquires specialized features of a brown adipocyte, an animal connective tissue cell involved in adaptive thermogenesis. Brown adipocytes contain multiple small droplets of triglycerides and a high number of mitochondria. GO:0050873]

defense response to Gram-positive bacterium [Reactions triggered in response to the presence of a Gram-positive bacterium that act to protect the cell or organism. GO:0050830]

fatty acid biosynthetic process [The chemical reactions and pathways resulting in the formation of a fatty acid, any of the aliphatic monocarboxylic acids that can be liberated by hydrolysis from naturally occurring fats and oils. Fatty acids are predominantly straight-chain acids of 4 to 24 carbon atoms, which may be saturated or unsaturated; branched fatty acids and hydroxy fatty acids also occur, and very long chain acids of over 30 carbons are found in waxes. GO:0006633]

lipid biosynthetic process [The chemical reactions and pathways resulting in the formation of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. GO:0008610]

lipid homeostasis [Any process involved in the maintenance of an internal steady state of lipid within an organism or cell. GO:0055088]

monounsaturated fatty acid biosynthetic process [The chemical reactions and pathways resulting in the formation of monounsaturated fatty acid.|For example, stearoyl-coenzyme A desaturase (Scd) catalyzes the desaturation of saturated fatty acids to monounsaturated fatty acids in mammals and yeast. GO:1903966]

positive regulation of cold-induced thermogenesis [Any process that activates or increases the frequency, rate or extent of cold-induced thermogenesis. GO:0120162]

response to bacterium [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a bacterium. GO:0009617]

response to fatty acid [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a fatty acid stimulus. GO:0070542]

response to nutrient [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nutrient stimulus. GO:0007584]

sebaceous gland development [The process whose specific outcome is the progression of the sebaceous gland over time, from its formation to the mature structure. GO:0048733]

sterol homeostasis [Any process involved in the maintenance of an internal steady state of sterol within an organism or cell. GO:0055092]

tarsal gland development [The process whose specific outcome is the progression of a tarsal gland over time, from its formation to the mature structure. GO:1903699]

triglyceride metabolic process [The chemical reactions and pathways involving triglyceride, any triester of glycerol. The three fatty acid residues may all be the same or differ in any permutation. Triglycerides are important components of plant oils, animal fats and animal plasma lipoproteins. GO:0006641]

unsaturated fatty acid biosynthetic process [The chemical reactions and pathways resulting in the formation of an unsaturated fatty acid, any fatty acid containing one or more double bonds between carbon atoms. GO:0006636]

white fat cell differentiation [The process in which a relatively unspecialized cell acquires specialized features of a white adipocyte, an animal connective tissue cell involved in energy storage. White adipocytes have cytoplasmic lipids arranged in a unique vacuole. GO:0050872]

MSigDB Signatures:

WP_LIVER_X_RECEPTOR_PATHWAY: Liver X receptor pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_LIVER_X_RECEPTOR_PATHWAY.html]

WP_CHOLESTEROL_BIOSYNTHESIS_PATHWAY_IN_HEPATOCYTES: Cholesterol biosynthesis pathway in hepatocytes [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CHOLESTEROL_BIOSYNTHESIS_PATHWAY_IN_HEPATOCYTES.html]

REACTOME_METABOLISM_OF_LIPIDS: Metabolism of lipids [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_LIPIDS.html]

REACTOME_FATTY_ACID_METABOLISM: Fatty acid metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_FATTY_ACID_METABOLISM.html]

WP_STEROL_REGULATORY_ELEMENT_BINDING_PROTEINS_SREBP_SIGNALING: Sterol regulatory element binding proteins SREBP signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_STEROL_REGULATORY_ELEMENT_BINDING_PROTEINS_SREBP_SIGNALING.html]

WP_CHOLESTEROL_METABOLISM_WITH_BLOCH_AND_KANDUTSCH_RUSSELL_PATHWAYS: Cholesterol metabolism with Bloch and Kandutsch Russell pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CHOLESTEROL_METABOLISM_WITH_BLOCH_AND_KANDUTSCH_RUSSELL_PATHWAYS.html]

WP_NUCLEAR_RECEPTORS_META_PATHWAY: Nuclear receptors meta pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_NUCLEAR_RECEPTORS_META_PATHWAY.html]

WP_OMEGA_9_FATTY_ACID_SYNTHESIS: Omega 9 fatty acid synthesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_OMEGA_9_FATTY_ACID_SYNTHESIS.html]

REACTOME_METABOLISM_OF_STEROIDS: Metabolism of steroids [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METABOLISM_OF_STEROIDS.html]

KEGG_PPAR_SIGNALING_PATHWAY: PPAR signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PPAR_SIGNALING_PATHWAY.html]

WP_PPAR_SIGNALING_PATHWAY: PPAR signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PPAR_SIGNALING_PATHWAY.html]

REACTOME_REGULATION_OF_CHOLESTEROL_BIOSYNTHESIS_BY_SREBP_SREBF: Regulation of cholesterol biosynthesis by SREBP (SREBF) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_REGULATION_OF_CHOLESTEROL_BIOSYNTHESIS_BY_SREBP_SREBF.html]

KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS: Biosynthesis of unsaturated fatty acids [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS.html]

WP_FATTY_ACID_BIOSYNTHESIS: Fatty acid biosynthesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FATTY_ACID_BIOSYNTHESIS.html]

WP_ADIPOGENESIS: Adipogenesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ADIPOGENESIS.html]

REACTOME_FATTY_ACYL_COA_BIOSYNTHESIS: Fatty acyl-CoA biosynthesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_FATTY_ACYL_COA_BIOSYNTHESIS.html]

REACTOME_NR1H2_NR1H3_REGULATE_GENE_EXPRESSION_LINKED_TO_LIPOGENESIS: NR1H2 & NR1H3 regulate gene expression linked to lipogenesis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NR1H2_NR1H3_REGULATE_GENE_EXPRESSION_LINKED_TO_LIPOGENESIS.html]

REACTOME_ACTIVATION_OF_GENE_EXPRESSION_BY_SREBF_SREBP: Activation of gene expression by SREBF (SREBP) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ACTIVATION_OF_GENE_EXPRESSION_BY_SREBF_SREBP.html]

WP_SREBF_AND_MIR33_IN_CHOLESTEROL_AND_LIPID_HOMEOSTASIS: SREBF and miR33 in cholesterol and lipid homeostasis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_SREBF_AND_MIR33_IN_CHOLESTEROL_AND_LIPID_HOMEOSTASIS.html]

REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS: Signaling by Nuclear Receptors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS.html]

WP_ANGIOPOIETIN_LIKE_PROTEIN_8_REGULATORY_PATHWAY: Angiopoietin like protein 8 regulatory pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ANGIOPOIETIN_LIKE_PROTEIN_8_REGULATORY_PATHWAY.html]

REACTOME_NR1H2_AND_NR1H3_MEDIATED_SIGNALING: NR1H2 and NR1H3-mediated signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NR1H2_AND_NR1H3_MEDIATED_SIGNALING.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes an enzyme involved in fatty acid biosynthesis, primarily the synthesis of oleic acid. The protein belongs to the fatty acid desaturase family and is an integral membrane protein located in the endoplasmic reticulum. Transcripts of approximately 3.9 and 5.2 kb, differing only by alternative polyadenlyation signals, have been detected. A gene encoding a similar enzyme is located on chromosome 4 and a pseudogene of this gene is located on chromosome 17. [provided by RefSeq, Sep 2015]

GeneCards Summary: SCD (Stearoyl-CoA Desaturase) is a Protein Coding gene. Diseases associated with SCD include Non-Alcoholic Fatty Liver Disease and Homocystinuria. Among its related pathways are Metabolism of steroids and NR1H2 and NR1H3-mediated signaling. Gene Ontology (GO) annotations related to this gene include iron ion binding and stearoyl-CoA 9-desaturase activity. An important paralog of this gene is SCD5.

UniProtKB/Swiss-Prot Summary: Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates [PMID: 15907797, PMID: 18765284]. Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA [PMID: 15907797, PMID: 18765284]. Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids [PMID: 15610069]. Plays an important role in lipid biosynthesis. Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation. Plays an important role in body energy homeostasis. Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides.

8. Cellular Location of Gene Product

General cytoplasmic expression. Mainly localized to the endoplasmic reticulum. Predicted location: Membrane [https://www.proteinatlas.org/ENSG00000099194/subcellular]

9. Mechanistic Information

Summary

The Stearoyl-CoA Desaturase (SCD) gene, encoding an enzyme crucial for lipid biosynthesis, particularly in the synthesis of oleic acid, becomes dysregulated in liver diseases due to its key role in lipid metabolism and energy homeostasis [CS: 8]. In conditions like hepatocellular carcinoma (HCC) and non-alcoholic steatohepatitis (NASH), there's a notable upregulation of SCD [CS: 8]. This upregulation can be linked to the liver's response to the altered metabolic demands of the disease state [CS: 7]. The enzyme produced by SCD introduces a double bond into saturated fatty acyl-CoA substrates, leading to the production of unsaturated fatty acids which are vital for maintaining the fluidity and integrity of cell membranes [CS: 10]. In disease states, this function becomes critical as the liver cells undergo stress and damage, requiring enhanced membrane repair and synthesis [CS: 7].

Furthermore, SCD plays a role in regulating gene expression involved in lipogenesis and mitochondrial fatty acid oxidation, key in managing energy resources during liver toxicity [CS: 7]. When the liver faces toxic events, such as those caused by high fat diets or alcohol-induced damage, the demand for energy and lipid synthesis escalates to repair and maintain cellular functions [CS: 7]. SCD's activity helps in these processes by contributing to the biosynthesis of crucial components like membrane phospholipids, cholesterol esters, and triglycerides [CS: 8]. This upregulation, therefore, acts as a compensatory mechanism to counteract the stress and damage inflicted on the liver cells, helping in maintaining cellular integrity and energy balance during the disease states [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: adipose tissue, brain, liver (tissue enhanced) [https://www.proteinatlas.org/ENSG00000099194/tissue]

Cell type enchanced: alveolar cells type 2, hepatocytes, kupffer cells, oligodendrocytes (group enriched) [https://www.proteinatlas.org/ENSG00000099194/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest