Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2H5BNX)

• DOT Name: Kelch domain-containing protein 7B (KLHDC7B)
• Gene Name: KLHDC7B
• Related Disease:
  Breast cancer
  Breast carcinoma
  Laryngeal carcinoma
  Advanced cancer
  Breast neoplasm
  Neoplasm
• UniProt ID: KLD7B_HUMAN
• Pfam ID: PF01344
• Sequence:
  MVLRSHPFPRQDRPQGSVPRAVPGSPVGPSTSTHSEDRHGPSSSVGTVIGTGTGGLVEAG
  GQPQPRSSETNGSPSPDPPPGLRGEGTREKSLDPLPQAAMPRGPAQPPAQRPPGPAASSS
  ARRSQPVPQLRKRSRCEIAPSSEQEVRPAASGDPQGEAPGEGGSPAGRSGALTEKQEEAR
  KLMVFLQRPGGWGVVEGPRKPSSRALEPATAAALRRRLDLGSCLDVLAFAQQHGEPGLAQ
  ETYALMSDNLLRVLGDPCLYRRLSAADRERILSLRTGRGRAVLGVLVLPSLYQGGRSGLP
  RGPRGEEPPAAAPVSLPLPAHLHVFNPRENTWRPLTQVPEEAPLRGCGLCTMHNYLFLAG
  GIRGSGAKAVCSNEVFCYNPLTNIWSQVRPMQQARAQLKLVALDGLLYAIGGECLYSMEC
  YDPRTDAWTPRAPLPAGTFPVAHEAVACRGDIYVTGGHLFYRLLRYSPVKDAWDECPYSA
  SHRRSSDIVALGGFLYRFDLLRGVGAAVMRYNTVTGSWSRAASLPLPAPAPLHCTTLGNT
  IYCLNPQVTATFTVSGGTAQFQAKELQPFPLGSTGVLSPFILTLPPEDRLQTSL

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Laryngeal carcinoma	DISNHCIV	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[3]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Kelch domain-containing protein 7B (KLHDC7B).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Kelch domain-containing protein 7B (KLHDC7B).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Kelch domain-containing protein 7B (KLHDC7B).	[14]

References

• [1] Expression of long non-coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple-negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death.Mol Oncol. 2019 Apr;13(4):909-927. doi: 10.1002/1878-0261.12446. Epub 2019 Feb 9.
• [2] Five genes as a novel signature for predicting the prognosis of patients with laryngeal cancer.J Cell Biochem. 2020 Aug;121(8-9):3804-3813. doi: 10.1002/jcb.29535. Epub 2019 Oct 31.
• [3] Characterization of Kelch domain-containing protein 7B in breast tumours and breast cancer cell lines.Oncol Lett. 2019 Sep;18(3):2853-2860. doi: 10.3892/ol.2019.10672. Epub 2019 Jul 26.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [14] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.