Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT91IAYT)

• DOT Name: Ceroid-lipofuscinosis neuronal protein 6 (CLN6)
• Synonyms: Protein CLN6
• Gene Name: CLN6
• Related Disease:
  Ceroid lipofuscinosis, neuronal, 6B (Kufs type)
  CLN6 disease
  Neuronal ceroid lipofuscinosis
• UniProt ID: CLN6_HUMAN
• Pfam ID: PF15156
• Sequence:
  MEATRRRQHLGATGGPGAQLGASFLQARHGSVSADEAARTAPFHLDLWFYFTLQNWVLDF
  GRPIAMLVFPLEWFPLNKPSVGDYFHMAYNVITPFLLLKLIERSPRTLPRSITYVSIIIF
  IMGASIHLVGDSVNHRLLFSGYQHHLSVRENPIIKNLKPETLIDSFELLYYYDEYLGHCM
  WYIPFFLILFMYFSGCFTASKAESLIPGPALLLVAPSGLYYWYLVTEGQIFILFIFTFFA
  MLALVLHQKRKRLFLDSNGLFLFSSFALTLLLVALWVAWLWNDPVLRKKYPGVIYVPEPW
  AFYTLHVSSRH

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ceroid lipofuscinosis, neuronal, 6B (Kufs type)	DISQDWLC	Definitive	Autosomal recessive	[1]
CLN6 disease	DIS8YLJJ	Definitive	Autosomal recessive	[2]
Neuronal ceroid lipofuscinosis	DIS9A4K4	Definitive	Autosomal recessive	[2]

6 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 Ceroid-lipofuscinosis neuronal protein 6 (CLN6).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ceroid-lipofuscinosis neuronal protein 6 (CLN6).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ceroid-lipofuscinosis neuronal protein 6 (CLN6).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ceroid-lipofuscinosis neuronal protein 6 (CLN6).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Ceroid-lipofuscinosis neuronal protein 6 (CLN6).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ceroid-lipofuscinosis neuronal protein 6 (CLN6).	[9]

2 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 Ceroid-lipofuscinosis neuronal protein 6 (CLN6).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Ceroid-lipofuscinosis neuronal protein 6 (CLN6).	[10]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] 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.
• [4] 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.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] 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.
• [9] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.