Details of Drug Off-Target (DOT)

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

• DOT Name: DAN domain family member 5 (DAND5)
• Synonyms: Cerberus-like protein 2; Cerl-2; Cysteine knot superfamily 1, BMP antagonist 3; Gremlin-3
• Gene Name: DAND5
• Related Disease:
  Cardiac disease
  Colorectal carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Congenital heart disease
• UniProt ID: DAND5_HUMAN
• Pfam ID: PF03045
• Sequence:
  MLLGQLSTLLCLLSGALPTGSGRPEPQSPRPQSWAAANQTWALGPGALPPLVPASALGSW
  KAFLGLQKARQLGMGRLQRGQDEVAAVTLPLNPQEVIQGMCKAVPFVQVFSRPGCSAIRL
  RNHLCFGHCSSLYIPGSDPTPLVLCNSCMPARKRWAPVVLWCLTGSSASRRRVKISTMLI
  EGCHCSPKA
• Function: Seems to play a role in the correct specification of the left-right axis. May antagonize NODAL and BMP4 signaling. Cystine knot-containing proteins play important roles during development, organogenesis, tissue growth and differentiation.
• Reactome Pathway:
  Regulation of signaling by NODAL (R-HSA-1433617)
  Signaling by NODAL (R-HSA-1181150)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac disease	DISVO1I5	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[3]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Congenital heart disease	DISQBA23	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DAN domain family member 5 (DAND5).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DAN domain family member 5 (DAND5).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DAN domain family member 5 (DAND5).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DAN domain family member 5 (DAND5).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of DAN domain family member 5 (DAND5).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of DAN domain family member 5 (DAND5).	[10]

References

• [1] Generation and characterization of a human iPS cell line from a patient-related control to study disease mechanisms associated with DAND5 p.R152H alteration.Stem Cell Res. 2018 May;29:202-206. doi: 10.1016/j.scr.2018.04.015. Epub 2018 Apr 28.
• [2] Elevated serum DAND5 is associated with metastasis and predicts poor prognosis in colorectal cancer.United European Gastroenterol J. 2017 Aug;5(5):725-734. doi: 10.1177/2050640616674838. Epub 2016 Oct 12.
• [3] Cost-effectiveness of second-line diagnostic investigations in patients included in the DANTE trial: a randomized controlled trial of lung cancer screening with low-dose computed tomography.Nucl Med Commun. 2019 May;40(5):508-516. doi: 10.1097/MNM.0000000000000993.
• [4] Elevated SP-1 transcription factor expression and activity drives basal and hypoxia-induced vascular endothelial growth factor (VEGF) expression in non-small cell lung cancer.J Biol Chem. 2012 Nov 16;287(47):39967-81. doi: 10.1074/jbc.M112.397042. Epub 2012 Sep 18.
• [5] Generation of human iPSC line from a patient with laterality defects and associated congenital heart anomalies carrying a DAND5 missense alteration.Stem Cell Res. 2017 Dec;25:152-156. doi: 10.1016/j.scr.2017.10.019. Epub 2017 Oct 31.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
• [10] 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.
• [11] 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.