Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM86B04)

• DOT Name: Ankyrin repeat domain-containing protein 6 (ANKRD6)
• Synonyms: Diversin
• Gene Name: ANKRD6
• Related Disease:
  Neural tube defect
  Non-small-cell lung cancer
  Psoriatic arthritis
  Breast cancer
  Breast carcinoma
  Knee osteoarthritis
• UniProt ID: ANKR6_HUMAN
• Pfam ID: PF00023 ; PF12796
• Sequence:
  MSQQDAVAALSERLLVAAYKGQTENVVQLINKGARVAVTKHGRTPLHLAANKGHLPVVQI
  LLKAGCDLDVQDDGDQTALHRATVVGNTEIIAALIHEGCALDRQDKDGNTALHEASWHGF
  SQSAKLLIKAGANVLAKNKAGNTALHLACQNSHSQSTRVLLLAGSRADLKNNAGDTCLHV
  AARYNHLSIIRLLLTAFCSVHEKNQAGDTALHVAAALNHKKVAKILLEAGADTTIVNNAG
  QTPLETARYHNNPEVALLLTKAPQVLRFSRGRSLRKKRERLKEERRAQSVPRDEVAQSKG
  SVSAGDTPSSEQAVARKEEAREEFLSASPEPRAKDDRRRKSRPKVSAFSDPTPPADQQPG
  HQKNLHAHNHPKKRNRHRCSSPPPPHEFRAYQLYTLYRGKDGKVMQAPINGCRCEPLINK
  LENQLEATVEEIKAELGSVQDKMNTKLGQMENKTQHQMRVLDKLMVERLSAERTECLNRL
  QQHSDTEKHEGEKRQISLVDELKTWCMLKIQNLEQKLSGDSRACRAKSTPSTCESSTGVD
  QLVVTAGPAAASDSSPPVVRPKEKALNSTATQRLQQELSSSDCTGSRLRNVKVQTALLPM
  NEAARSDQQAGPCVNRGTQTKKSGKSGPTRHRAQQPAASSTCGQPPPATGSEQTGPHIRD
  TSQALELTQYFFEAVSTQMEKWYERKIEEARSQANQKAQQDKATLKEHIKSLEEELAKLR
  TRVQKEN
• Function: Recruits CKI-epsilon to the beta-catenin degradation complex that consists of AXN1 or AXN2 and GSK3-beta and allows efficient phosphorylation of beta-catenin, thereby inhibiting beta-catenin/Tcf signals.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neural tube defect	DIS5J95E	Definitive	Genetic Variation	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Psoriatic arthritis	DISLWTG2	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Limited	Biomarker	[4]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[4]
Knee osteoarthritis	DISLSNBJ	Limited	Genetic Variation	[5]

7 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 Ankyrin repeat domain-containing protein 6 (ANKRD6).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ankyrin repeat domain-containing protein 6 (ANKRD6).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Ankyrin repeat domain-containing protein 6 (ANKRD6).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ankyrin repeat domain-containing protein 6 (ANKRD6).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ankyrin repeat domain-containing protein 6 (ANKRD6).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ankyrin repeat domain-containing protein 6 (ANKRD6).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ankyrin repeat domain-containing protein 6 (ANKRD6).	[12]

References

• [1] Genetic studies of ANKRD6 as a molecular switch between Wnt signaling pathways in human neural tube defects.Birth Defects Res A Clin Mol Teratol. 2015 Jan;103(1):20-6. doi: 10.1002/bdra.23273. Epub 2014 Sep 8.
• [2] Diversin increases the proliferation and invasion ability of non-small-cell lung cancer cells via JNK pathway.Cancer Lett. 2014 Mar 28;344(2):232-8. doi: 10.1016/j.canlet.2013.10.033. Epub 2013 Nov 15.
• [3] Variants of the ankyrin repeat domain 6 gene (ANKRD6) and muscle and physical activity phenotypes among European-derived American adults.J Strength Cond Res. 2012 Jul;26(7):1740-8. doi: 10.1519/JSC.0b013e31825c2bef.
• [4] Diversin is overexpressed in breast cancer and accelerates cell proliferation and invasion.PLoS One. 2014 May 23;9(5):e98591. doi: 10.1371/journal.pone.0098591. eCollection 2014.
• [5] Genetic Determinants of Radiographic Knee Osteoarthritis in African Americans.J Rheumatol. 2017 Nov;44(11):1652-1658. doi: 10.3899/jrheum.161488. Epub 2017 Sep 15.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.