Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMDZ56K)

• DOT Name: Lipid transferase CIDEC (CIDEC)
• Synonyms: Cell death activator CIDE-3; Cell death-inducing DFFA-like effector protein C; Fat-specific protein FSP27 homolog
• Gene Name: CIDEC
• Related Disease:
  Allergic contact dermatitis
  Metabolic disorder
  Alcoholic hepatitis
  Arteriosclerosis
  Atherosclerosis
  Familial partial lipodystrophy
  Hepatitis B virus infection
  Lipodystrophy
  Lung adenocarcinoma
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Obesity
  Partial lipodystrophy
  CIDEC-related familial partial lipodystrophy
  Fatty liver disease
• UniProt ID: CIDEC_HUMAN
• Pfam ID: PF02017
• Sequence:
  MEYAMKSLSLLYPKSLSRHVSVRTSVVTQQLLSEPSPKAPRARPCRVSTADRSVRKGIMA
  YSLEDLLLKVRDTLMLADKPFFLVLEEDGTTVETEEYFQALAGDTVFMVLQKGQKWQPPS
  EQGTRHPLSLSHKPAKKIDVARVTFDLYKLNPQDFIGCLNVKATFYDTYSLSYDLHCCGA
  KRIMKEAFRWALFSMQATGHVLLGTSCYLQQLLDATEEGQPPKGKASSLIPTCLKILQ
• Function: Lipid transferase specifically expressed in white adipose tissue, which promotes unilocular lipid droplet formation by mediating lipid droplet fusion. Lipid droplet fusion promotes their enlargement, restricting lipolysis and favoring lipid storage. Localizes on the lipid droplet surface, at focal contact sites between lipid droplets, and mediates atypical lipid droplet fusion by undergoing liquid-liquid phase separation (LLPS) and promoting directional net neutral lipid transfer from the smaller to larger lipid droplets. The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair. Its role in neutral lipid transfer and lipid droplet enlargement is activated by the interaction with PLIN1. May also act as a CEBPB coactivator in the white adipose tissue to control the expression of a subset of CEBPB downstream target genes, including SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. When overexpressed in preadipocytes, induces apoptosis or increases cell susceptibility to apoptosis induced by serum deprivation or TGFB treatment.
• Tissue Specificity: Expressed mainly in adipose tissue, small intestine, heart, colon and stomach and, at lower levels, in brain, kidney and liver.
• KEGG Pathway: Regulation of lipolysis in adipocytes (hsa04923)
• Reactome Pathway: Lipid particle organization (R-HSA-8964572)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic contact dermatitis	DISFFVF9	Definitive	Biomarker	[1]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[2]
Alcoholic hepatitis	DISA7SH0	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Posttranslational Modification	[4]
Atherosclerosis	DISMN9J3	Strong	Posttranslational Modification	[4]
Familial partial lipodystrophy	DISFVL9J	Strong	Biomarker	[5]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[6]
Lipodystrophy	DIS3SGVD	Strong	Biomarker	[5]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[9]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[10]
Obesity	DIS47Y1K	Strong	Biomarker	[11]
Partial lipodystrophy	DIS2HKKW	Strong	Genetic Variation	[12]
CIDEC-related familial partial lipodystrophy	DISG7U2L	Supportive	Autosomal recessive	[12]
Fatty liver disease	DIS485QZ	Limited	Altered Expression	[13]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Lipid transferase CIDEC (CIDEC).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lipid transferase CIDEC (CIDEC).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lipid transferase CIDEC (CIDEC).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Lipid transferase CIDEC (CIDEC).	[17]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Lipid transferase CIDEC (CIDEC).	[18]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Lipid transferase CIDEC (CIDEC).	[19]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Lipid transferase CIDEC (CIDEC).	[20]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Lipid transferase CIDEC (CIDEC).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Lipid transferase CIDEC (CIDEC).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lipid transferase CIDEC (CIDEC).	[22]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Lipid transferase CIDEC (CIDEC).	[23]
EPI-001	DMYWV81	Investigative	EPI-001 increases the expression of Lipid transferase CIDEC (CIDEC).	[24]
T0070907	DMTKSVO	Investigative	T0070907 decreases the expression of Lipid transferase CIDEC (CIDEC).	[23]

References

• [1] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [2] A physiological role for fat specific protein 27/cell death-inducing DFF45-like effector C in adipose and liver.Biol Pharm Bull. 2010;33(3):346-50. doi: 10.1248/bpb.33.346.
• [3] Fat-Specific Protein 27/CIDEC Promotes Development of Alcoholic Steatohepatitis in Mice and Humans.Gastroenterology. 2015 Oct;149(4):1030-41.e6. doi: 10.1053/j.gastro.2015.06.009. Epub 2015 Jun 20.
• [4] Therapeutic silencing of FSP27 reduces the progression of atherosclerosis in Ldlr(-/-) mice.Atherosclerosis. 2018 Aug;275:43-49. doi: 10.1016/j.atherosclerosis.2018.05.045. Epub 2018 May 24.
• [5] Clinical review#: Lipodystrophies: genetic and acquired body fat disorders.J Clin Endocrinol Metab. 2011 Nov;96(11):3313-25. doi: 10.1210/jc.2011-1159. Epub 2011 Aug 24.
• [6] Hepatitis B virus prevents excessive viral production via reduction of cell death-inducing DFF45-like effectors.J Gen Virol. 2017 Jul;98(7):1762-1773. doi: 10.1099/jgv.0.000813.
• [7] Silencing of ARL14 Gene Induces Lung Adenocarcinoma Cells to a Dormant State.Front Cell Dev Biol. 2019 Oct 15;7:238. doi: 10.3389/fcell.2019.00238. eCollection 2019.
• [8] Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma.Oncotarget. 2017 Mar 21;8(12):19389-19402. doi: 10.18632/oncotarget.14288.
• [9] Amelioration of diet-induced steatohepatitis in mice following combined therapy with ASO-Fsp27 and fenofibrate.J Lipid Res. 2017 Nov;58(11):2127-2138. doi: 10.1194/jlr.M077941. Epub 2017 Sep 5.
• [10] Emerging Mechanisms of GH-Induced Lipolysis and Insulin Resistance.Pediatr Endocrinol Rev. 2019 Sep;17(1):4-16. doi: 10.17458/per.vol17.2019.s.ghlipolysisandinsulinresistance.
• [11] FSP27 and Links to Obesity and Diabetes Mellitus.Curr Obes Rep. 2019 Sep;8(3):255-261. doi: 10.1007/s13679-019-00343-3.
• [12] Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. EMBO Mol Med. 2009 Aug;1(5):280-7. doi: 10.1002/emmm.200900037.
• [13] Fat-specific protein 27b is regulated by hepatic peroxisome proliferator-activated receptor in hepatic steatosis.Endocr J. 2020 Jan 28;67(1):37-44. doi: 10.1507/endocrj.EJ19-0296. Epub 2019 Sep 27.
• [14] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [15] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [16] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [17] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [18] Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):292-8.
• [19] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [20] Effects of chronic rosiglitazone therapy on gene expression in human adipose tissue in vivo in patients with type 2 diabetes. J Clin Endocrinol Metab. 2007 Feb;92(2):720-4.
• [21] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [22] Microarray analysis of bisphenol A-induced changes in gene expression in human oral epithelial cells. Acta Biochim Biophys Sin (Shanghai). 2007 Nov;39(11):879-84. doi: 10.1111/j.1745-7270.2007.00351.x.
• [23] Effects of Perinatal Exposure to Dibutyltin Chloride on Fat and Glucose Metabolism in Mice, and Molecular Mechanisms, in Vitro. Environ Health Perspect. 2018 May 21;126(5):057006. doi: 10.1289/EHP3030. eCollection 2018 May.
• [24] EPI-001 is a selective peroxisome proliferator-activated receptor-gamma modulator with inhibitory effects on androgen receptor expression and activity in prostate cancer. Oncotarget. 2015 Feb 28;6(6):3811-24.