Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY9IAKW)

• DOT Name: StAR-related lipid transfer protein 8 (STARD8)
• Synonyms: Deleted in liver cancer 3 protein; DLC-3; START domain-containing protein 8; StARD8; START-GAP3
• Gene Name: STARD8
• Related Disease:
  Colorectal carcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Congenital diaphragmatic hernia
  Disorder of sexual differentiation
  Gastric cancer
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Colorectal neoplasm
• UniProt ID: STAR8_HUMAN
• Pfam ID: PF00620 ; PF01852
• Sequence:
  MTLNNCASMKLEVHFQSKQNEDSEEEEQCTISSHWAFQQESKCWSPMGSSDLLAPPSPGL
  PATSSCESVLTELSATSLPVITVSLPPEPADLPLPGRAPSSSDRPLLSPTQGQEGPQDKA
  KKRHRNRSFLKHLESLRRKEKSGSQQAEPKHSPATSEKVSKASSFRSCRGFLSAGFYRAK
  NWAATSAGGSGANTRKAWEAWPVASFRHPQWTHRGDCLVHVPGDHKPGTFPRSLSIESLC
  PEDGHRLADWQPGRRWGCEGRRGSCGSTGSHASTYDNLPELYPAEPVMVGAEAEDEDDEE
  SGGSYAHLDDILQHVWGLQQRVELWSRAMYPDLGPGDEEEEEATSSVEIATVEVKCQAEA
  LSQMEVPAHGESPAWAQAEVQPAVLAPAQAPAEAEPVAQEEAEAPAPAPAPAPAQDSEQE
  AHSGGEPTFASSLSVEEGHSISDTVASSSELDSSGNSMNEAEAAGPLAGLQASMPRERRD
  SGVGASLTRPCRKLRWHSFQNSHRPSLNSESLEINRQFAGQINLLHKGSLLRLTAFMEKY
  TVPHKQGWVWSMPKFMRRNKTPDYRGQHVFGVPPLIHVQRTGQPLPQSIQQAMRYLRSQC
  LDQVGIFRKSGVKSRIQNLRQMNETSPDNVCYEGQSAYDVADLLKQYFRDLPEPIFTSKL
  TTTFLQIYQLLPKDQWLAAAQAATLLLPDENREVLQTLLYFLSDIASAEENQMTAGNLAV
  CLAPSIFHLNVSKKDSPSPRIKSKRSLIGRPGPRDLSDNMAATQGLSHMISDCKKLFQVP
  QDMVLQLCSSYSAAELSPPGPALAELRQAQAAGVSLSLYMEENIQDLLRDAAERFKGWMS
  VPGPQHTELACRKAPDGHPLRLWKASTEVAAPPAVVLHRVLRERALWDEDLLRAQVLEAL
  MPGVELYHYVTDSMAPHPCRDFVVLRMWRSDLPRGGCLLVSQSLDPEQPVPESGVRALML
  TSQYLMEPCGLGRSRLTHICRADLRGRSPDWYNKVFGHLCAMEVAKIRDSFPTLQAAGPE
  TKL
• Function: Accelerates GTPase activity of RHOA and CDC42, but not RAC1. Stimulates the hydrolysis of phosphatidylinositol 4,5-bisphosphate by PLCD1.
• Tissue Specificity: Widely expressed with highest levels in kidney, lung and placenta.
• Reactome Pathway:
  RHOB GTPase cycle (R-HSA-9013026)
  CDC42 GTPase cycle (R-HSA-9013148)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Congenital diaphragmatic hernia	DIS0IPVU	Strong	Biomarker	[5]
Disorder of sexual differentiation	DISRMAEZ	Strong	Biomarker	[6]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Altered Expression	[4]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[4]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[2]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of StAR-related lipid transfer protein 8 (STARD8).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of StAR-related lipid transfer protein 8 (STARD8).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of StAR-related lipid transfer protein 8 (STARD8).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of StAR-related lipid transfer protein 8 (STARD8).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of StAR-related lipid transfer protein 8 (STARD8).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of StAR-related lipid transfer protein 8 (STARD8).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of StAR-related lipid transfer protein 8 (STARD8).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of StAR-related lipid transfer protein 8 (STARD8).	[15]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of StAR-related lipid transfer protein 8 (STARD8).	[16]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of StAR-related lipid transfer protein 8 (STARD8).	[13]

References

• [1] Genomic and epigenomic integration identifies a prognostic signature in colon cancer.Clin Cancer Res. 2011 Mar 15;17(6):1535-45. doi: 10.1158/1078-0432.CCR-10-2509. Epub 2011 Jan 28.
• [2] Gastric cancer cells escape metabolic stress via the DLC3/MACC1 axis.Theranostics. 2019 Apr 6;9(7):2100-2114. doi: 10.7150/thno.29538. eCollection 2019.
• [3] Convergence of mutation and epigenetic alterations identifies common genes in cancer that predict for poor prognosis.PLoS Med. 2008 May 27;5(5):e114. doi: 10.1371/journal.pmed.0050114.
• [4] Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth.Oncogene. 2007 Jul 5;26(31):4580-9. doi: 10.1038/sj.onc.1210244. Epub 2007 Feb 5.
• [5] Xq12q13.1 microduplication encompassing the EFNB1 gene in a boy with congenital diaphragmatic hernia.Eur J Med Genet. 2011 Sep-Oct;54(5):e525-7. doi: 10.1016/j.ejmg.2011.06.011. Epub 2011 Jul 14.
• [6] A Case of Two Sisters Suffering from 46,XY Gonadal Dysgenesis and Carrying a Mutation of a Novel Candidate Sex-Determining Gene STARD8 on the X Chromosome.Sex Dev. 2018;12(4):191-195. doi: 10.1159/000489692. Epub 2018 Jun 8.
• [7] Downregulation of STARD8 in gastric cancer and its involvement in gastric cancer progression.Onco Targets Ther. 2018 May 21;11:2955-2961. doi: 10.2147/OTT.S154524. eCollection 2018.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] 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.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [16] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.