Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3SW5UC)

• DOT Name: Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1)
• Synonyms: Hydrolethalus syndrome protein 1
• Gene Name: HYLS1
• Related Disease:
  Hydrolethalus syndrome 1
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Cerebral palsy
  Joubert syndrome 1
  Pheochromocytoma
  Von hippel-lindau disease
  Breast cancer
  Breast carcinoma
  Hydrolethalus syndrome
  Joubert syndrome
  Age-related macular degeneration
  Diabetic macular edema
  High blood pressure
  Neoplasm
  Retinal vein occlusion
• UniProt ID: HYLS1_HUMAN
• Pfam ID: PF15311
• Sequence:
  MEELLPDGQIWANMDPEERMLAAATAFTHICAGQGEGDVRREAQSIQYDPYSKASVAPGK
  RPALPVQLQYPHVESNVPSETVSEASQRLRKPVMKRKVLRRKPDGEVLVTDESIISESES
  GTENDQDLWDLRQRLMNVQFQEDKESSFDVSQKFNLPHEYQGISQDQLICSLQREGMGSP
  AYEQDLIVASRPKSFILPKLDQLSRNRGKTDRVARYFEYKRDWDSIRLPGEDHRKELRWG
  VREQMLCRAEPQSKPQHIYVPNNYLVPTEKKRSALRWGVRCDLANGVIPRKLPFPLSPS
• Function: Plays a role in ciliogenesis.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hydrolethalus syndrome 1	DIS9GYP0	Definitive	Autosomal recessive	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[4]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[4]
Cerebral palsy	DIS82ODL	Strong	Biomarker	[5]
Joubert syndrome 1	DISC9Q82	Strong	GermlineCausalMutation	[6]
Pheochromocytoma	DIS56IFV	Strong	Biomarker	[7]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[8]
Hydrolethalus syndrome	DISX56R3	Supportive	Autosomal recessive	[1]
Joubert syndrome	DIS7P5CO	Supportive	Autosomal recessive	[6]
Age-related macular degeneration	DIS0XS2C	Limited	Biomarker	[9]
Diabetic macular edema	DIS162FN	Limited	Genetic Variation	[9]
High blood pressure	DISY2OHH	Limited	Biomarker	[10]
Neoplasm	DISZKGEW	Limited	Biomarker	[11]
Retinal vein occlusion	DISSVWOE	Limited	Genetic Variation	[9]

18 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 Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[16]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[17]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[19]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[20]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[21]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[22]
Lindane	DMB8CNL	Approved	Lindane decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[22]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[27]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[17]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[22]

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 Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1).	[24]

References

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• [4] Healthy Lifestyle During the Midlife Is Prospectively Associated With Less Subclinical Carotid Atherosclerosis: The Study of Women's Health Across the Nation.J Am Heart Assoc. 2018 Dec 4;7(23):e010405. doi: 10.1161/JAHA.118.010405.
• [5] Percutaneous Hamstring Lengthening Surgery is as Effective as Open Lengthening in Children With Cerebral Palsy.J Pediatr Orthop. 2019 Aug;39(7):366-371. doi: 10.1097/BPO.0000000000000924.
• [6] A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome. Clin Genet. 2016 Jun;89(6):739-43. doi: 10.1111/cge.12752. Epub 2016 Mar 4.
• [7] Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus.Lancet. 1991 May 4;337(8749):1052-4. doi: 10.1016/0140-6736(91)91705-y.
• [8] Validation of the European Health Literacy Survey Questionnaire in Women With Breast Cancer.Cancer Nurs. 2018 Mar/Apr;41(2):E40-E48. doi: 10.1097/NCC.0000000000000475.
• [9] Low health literacy levels in patients with chronic retinal disease.BMC Ophthalmol. 2019 Aug 8;19(1):174. doi: 10.1186/s12886-019-1191-1.
• [10] The role of lifestyle behaviour on the risk of hypertension in the SUN cohort: The hypertension preventive score.Prev Med. 2019 Jun;123:171-178. doi: 10.1016/j.ypmed.2019.03.026. Epub 2019 Mar 19.
• [11] Central nervous system lesions in von Hippel-Lindau syndrome.J Neurol Neurosurg Psychiatry. 1992 Oct;55(10):898-901. doi: 10.1136/jnnp.55.10.898.
• [12] 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.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [18] 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.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [22] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] 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.
• [25] 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.
• [26] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [27] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.