Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBT9GZ8)

• DOT Name: Armadillo repeat-containing protein 12 (ARMC12)
• Gene Name: ARMC12
• Related Disease:
  Neoplasm
  Neuroblastoma
• UniProt ID: ARM12_HUMAN
• Pfam ID: PF04826
• Sequence:
  MGKSIPQYLGQLDIRKSVVSLATGAGAIYLLYKAIKAGIKCKPPLCSNSPICIARLAVER
  ERHGRDSGELRRLLNSLECKQDEYAKSMILHSITRCVYLLEAEASACTTDDIVLLGYMLD
  DKDNSVKTQALNTLKAFSGIRKFRLKIQEHSIKVLELISTIWDTELHIAGLRLLNNLPLP
  DYVHPQLRRVMPALMEILQSDYILAQVQAVRLLSYLAQKNDLLYDILNCQVHSNFLNLFQ
  PTQSGSLLYEVLVFAERLSEGRNAPHYHVVKWHYNEQSLHESLFGEESRLADRLLALVIH
  PEEDVQIQACKVIVSLQYPQDLRARPSSCQPSRSYFKNTE
• Function: Essential for male fertility and sperm mitochondrial sheath formation. Required for proper mitochondrial elongation and coiling along the flagellum during the formation of the mitochondrial sheath. Facilitates the growth and aggressiveness of neuroblastoma cells. Increases the EZH2 activity and H3K27me3 levels in a RBBP4-dependent manner, and facilitates the enrichment of polycomb repressive complex 2 and H3K27me3 on gene promoters, resulting in transcriptional repression of tumor suppressors affecting the proliferation, invasion, and metastasis of tumor cells.
• Tissue Specificity: Testis-specific . Expressed at higher levels in neuroblastoma tissues and cell lines, than those of normal dorsal ganglia (at protein level) . Expressed in breast cancer, colon cancer, hepatocellular carcinoma, lung cancer, pancreas cancer, prostate cancer, renal cancer and gastric cancer, but not in their normal counterparts .

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Limited	Altered Expression	[1]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Armadillo repeat-containing protein 12 (ARMC12).	[2]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Armadillo repeat-containing protein 12 (ARMC12).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Armadillo repeat-containing protein 12 (ARMC12).	[4]

References

• [1] Armadillo repeat containing 12 promotes neuroblastoma progression through interaction with retinoblastoma binding protein 4.Nat Commun. 2018 Jul 19;9(1):2829. doi: 10.1038/s41467-018-05286-2.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [4] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.