Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTAJJ63)

• DOT Name: Cerberus (CER1)
• Synonyms: Cerberus-related protein; DAN domain family member 4
• Gene Name: CER1
• Related Disease:
  Fibrosarcoma
  Neoplasm
  Osteoporosis
  Severe combined immunodeficiency
  Autism spectrum disorder
  Intellectual disability
• UniProt ID: CER1_HUMAN
• Pfam ID: PF03045
• Sequence:
  MHLLLFQLLVLLPLGKTTRHQDGRQNQSSLSPVLLPRNQRELPTGNHEEAEEKPDLFVAV
  PHLVATSPAGEGQRQREKMLSRFGRFWKKPEREMHPSRDSDSEPFPPGTQSLIQPIDGMK
  MEKSPLREEAKKFWHHFMFRKTPASQGVILPIKSHEVHWETCRTVPFSQTITHEGCEKVV
  VQNNLCFGKCGSVHFPGAAQHSHTSCSHCLPAKFTTMHLPLNCTELSSVIKVVMLVEECQ
  CKVKTEHEDGHILHAGSQDSFIPGVSA
• Function: Cytokine that may play a role in anterior neural induction and somite formation during embryogenesis in part through a BMP-inhibitory mechanism. Can regulate Nodal signaling during gastrulation as well as the formation and patterning of the primitive streak.
• KEGG Pathway: Wnt sig.ling pathway (hsa04310)
• Reactome Pathway:
  Regulation of signaling by NODAL (R-HSA-1433617)
  Signaling by BMP (R-HSA-201451)
  Signaling by NODAL (R-HSA-1181150)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[3]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Disputed	Biomarker	[5]
Intellectual disability	DISMBNXP	Disputed	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Cerberus (CER1).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Cerberus (CER1).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Cerberus (CER1).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cerberus (CER1).	[10]

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 affects the methylation of Cerberus (CER1).	[9]

References

• [1] Similar regions of human chromosome 3 are eliminated from or retained in human/human and human/mouse microcell hybrids during tumor growth in severe combined immunodeficient (SCID) mice.Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1136-41. doi: 10.1073/pnas.98.3.1136.
• [2] Segmental duplications and evolutionary plasticity at tumor chromosome break-prone regions.Genome Res. 2008 Mar;18(3):370-9. doi: 10.1101/gr.7010208. Epub 2008 Jan 29.
• [3] CER1 gene variations associated with bone mineral density, bone markers, and early menopause in postmenopausal women.Hum Genomics. 2013 Oct 18;7(1):21. doi: 10.1186/1479-7364-7-21.
• [4] A 1-Mb PAC contig spanning the common eliminated region 1 (CER1) in microcell hybrid-derived SCID tumors.Genomics. 1999 Dec 1;62(2):147-55. doi: 10.1006/geno.1999.5952.
• [5] Cerberus, an Access Control Scheme for Enforcing Least Privilege in Patient Cohort Study Platforms : A Comprehensive Access Control Scheme Applied to the GENIDA Project - Study of Genetic Forms of Intellectual Disabilities and Autism Spectrum Disorders.J Med Syst. 2017 Nov 16;42(1):1. doi: 10.1007/s10916-017-0844-y.
• [6] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [7] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [8] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [9] 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.
• [10] BET bromodomain inhibitors suppress EWS-FLI1-dependent transcription and the IGF1 autocrine mechanism in Ewing sarcoma. Oncotarget. 2016 Jul 12;7(28):43504-43517. doi: 10.18632/oncotarget.9762.