Details of Drug Off-Target (DOT)

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

• DOT Name: Noelin (OLFM1)
• Synonyms: Neuronal olfactomedin-related ER localized protein; Olfactomedin-1
• Gene Name: OLFM1
• Related Disease:
  Periodontitis
  Alzheimer disease
  Amyloidosis
  Colorectal carcinoma
  Dementia
  Disorder of orbital region
  Hepatocellular carcinoma
  Nephrotic syndrome
  Obesity
  Prostate cancer
  Prostate neoplasm
  Tourette syndrome
  Ewing sarcoma
  Rhabdomyosarcoma
  Amyotrophic lateral sclerosis
  Phenylketonuria
• UniProt ID: NOE1_HUMAN
• PDB ID: 4XAT; 6QHJ
• Pfam ID: PF12308 ; PF02191
• Sequence:
  MSVPLLKIGVVLSTMAMITNWMSQTLPSLVGLNTTKLSAAGGGTLDRSTGVLPTNPEESW
  QVYSSAQDSEGRCICTVVAPQQTMCSRDARTKQLRQLLEKVQNMSQSIEVLDRRTQRDLQ
  YVEKMENQMKGLESKFKQVEESHKQHLARQFKAIKAKMDELRPLIPVLEEYKADAKLVLQ
  FKEEVQNLTSVLNELQEEIGAYDYDELQSRVSNLEERLRACMQKLACGKLTGISDPVTVK
  TSGSRFGSWMTDPLAPEGDNRVWYMDGYHNNRFVREYKSMVDFMNTDNFTSHRLPHPWSG
  TGQVVYNGSIYFNKFQSHIIIRFDLKTETILKTRSLDYAGYNNMYHYAWGGHSDIDLMVD
  ESGLWAVYATNQNAGNIVVSRLDPVSLQTLQTWNTSYPKRSAGEAFIICGTLYVTNGYSG
  GTKVHYAYQTNASTYEYIDIPFQNKYSHISMLDYNPKDRALYAWNNGHQILYNVTLFHVI
  RSDEL
• Function: Contributes to the regulation of axonal growth in the embryonic and adult central nervous system by inhibiting interactions between RTN4R and LINGO1. Inhibits RTN4R-mediated axon growth cone collapse. May play an important role in regulating the production of neural crest cells by the neural tube. May be required for normal responses to olfactory stimuli.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Periodontitis	DISI9JOI	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Amyloidosis	DISHTAI2	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Dementia	DISXL1WY	Strong	Biomarker	[3]
Disorder of orbital region	DISH0ECJ	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[7]
Obesity	DIS47Y1K	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[9]
Tourette syndrome	DISX9D54	Strong	Biomarker	[10]
Ewing sarcoma	DISQYLV3	moderate	Biomarker	[11]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[11]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[12]
Phenylketonuria	DISCU56J	Limited	Genetic Variation	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Noelin (OLFM1).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Noelin (OLFM1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Noelin (OLFM1).	[16]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Noelin (OLFM1).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Noelin (OLFM1).	[19]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Noelin (OLFM1).	[20]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Noelin (OLFM1).	[21]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Noelin (OLFM1).	[22]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Noelin (OLFM1).	[23]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Noelin (OLFM1).	[24]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Noelin (OLFM1).	[25]
Estrone	DM5T6US	Approved	Estrone increases the expression of Noelin (OLFM1).	[24]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Noelin (OLFM1).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Noelin (OLFM1).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Noelin (OLFM1).	[25]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Noelin (OLFM1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Noelin (OLFM1).	[28]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Noelin (OLFM1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Noelin (OLFM1).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Noelin (OLFM1).	[29]
Manganese	DMKT129	Investigative	Manganese increases the expression of Noelin (OLFM1).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Noelin (OLFM1).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Noelin (OLFM1).	[27]

References

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• [10] A t(3;9)(q25.1;q34.3) translocation leading to OLFM1 fusion transcripts in Gilles de la Tourette syndrome, OCD and ADHD.Psychiatry Res. 2015 Feb 28;225(3):268-75. doi: 10.1016/j.psychres.2014.12.028. Epub 2014 Dec 30.
• [11] Artificial neural network inference (ANNI): a study on gene-gene interaction for biomarkers in childhood sarcomas.PLoS One. 2014 Jul 15;9(7):e102483. doi: 10.1371/journal.pone.0102483. eCollection 2014.
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• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [22] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [23] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [24] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [25] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [26] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
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• [28] 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.
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• [30] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.