Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNQOJ6S)

• DOT Name: Coiled-coil domain-containing protein 170 (CCDC170)
• Gene Name: CCDC170
• Related Disease:
  Bipolar disorder
  Cardiovascular disease
  Estrogen-receptor positive breast cancer
  Major depressive disorder
  Neoplasm
  Schizophrenia
  Endometriosis
  Nasopharyngeal carcinoma
  Breast cancer
  Breast carcinoma
  Osteoporosis
• UniProt ID: CC170_HUMAN
• Sequence:
  MSLDCTSHIALGAASPAPEETYDHLSEVPVTREQLNHYRNVAQNARSELAATLVKFECAQ
  SELQDLRSKMLSKEVSCQELKAEMESYKENNARKSSLLTSLRDRVQELEEESAALSTSKI
  RTEITAHAAIKENQELKKKVVELNEKLQKCSKENEENKKQVSKNCRKHEEFLTQLRDCLD
  PDERNDKASDEDLILKLRDLRKENEFVKGQIVILEETINVHEMEAKASRETIMRLASEVN
  REQKKAASCTEEKEKLNQDLLSAVEAKEALEREVKIFQERLLAGQQVWDASKQEVSLLKK
  SSSELEKSLKASQDAVTTSQSQYFSFREKIAALLRGRLSMTGSTEDTILEKIREMDSREE
  SRDRMVSQLEAQISELVEQLGKESGFHQKALQRAQKAENMLETLQGQLTHLEAELVSGGV
  LRDNLNFEKQKYLKFLDQLSQKMKLDQMAAELGFDMRLDVVLARTEQLVRLESNAVIENK
  TIAHNLQRKLKTQKERLESKELHMSLLRQKIAQLEEEKQARTALVVERDNAHLTIRNLQK
  KVERLQKELNTCRDLHTELKAKLADTNELKIKTLEQTKAIEDLNKSRDQLEKMKEKAEKK
  LMSVKSELDTTEHEAKENKERARNMIEVVTSEMKTLKKSLEEAEKREKQLADFREVVSQM
  LGLNVTSLALPDYEIIKCLERLVHSHQHHFVTCACLKDVTTGQERHPQGHLQLLH
• Function: Plays a role in Golgi-associated microtubules organization and stabilization.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[3]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
Endometriosis	DISX1AG8	moderate	Genetic Variation	[4]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Limited	Biomarker	[6]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[7]
Osteoporosis	DISF2JE0	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coiled-coil domain-containing protein 170 (CCDC170).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Coiled-coil domain-containing protein 170 (CCDC170).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Coiled-coil domain-containing protein 170 (CCDC170).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Coiled-coil domain-containing protein 170 (CCDC170).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coiled-coil domain-containing protein 170 (CCDC170).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Coiled-coil domain-containing protein 170 (CCDC170).	[12]

References

• [1] GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.Am J Psychiatry. 2019 Aug 1;176(8):651-660. doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.
• [2] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [3] Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers.Nat Commun. 2014 Aug 7;5:4577. doi: 10.1038/ncomms5577.
• [4] Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism.Nat Commun. 2017 May 24;8:15539. doi: 10.1038/ncomms15539.
• [5] Multigene pathway-based analyses identify nasopharyngeal carcinoma risk associations for cumulative adverse effects of TERT-CLPTM1L and DNA double-strand breaks repair.Int J Cancer. 2014 Oct 1;135(7):1634-45. doi: 10.1002/ijc.28802. Epub 2014 Mar 4.
• [6] Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer.Calcif Tissue Int. 2017 Nov;101(5):489-500. doi: 10.1007/s00223-017-0308-x. Epub 2017 Jul 31.
• [7] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [8] Association of RMND1/CCDC170-ESR1 single nucleotide polymorphisms with hip fracture and osteoporosis in postmenopausal women.Climacteric. 2019 Feb;22(1):97-104. doi: 10.1080/13697137.2018.1538339. Epub 2019 Jan 2.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.