Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2ENKKV)

• DOT Name: Ankyrin repeat domain-containing protein 26 (ANKRD26)
• Gene Name: ANKRD26
• Related Disease:
  Thrombocytopenia 2
  Thyroid gland papillary carcinoma
  Acquired thrombocytopenia
  Acute leukaemia
  Acute myelogenous leukaemia
  Advanced cancer
  Childhood myelodysplastic syndrome
  Coagulation defect
  Gray platelet syndrome
  Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
  leukaemia
  Li-Fraumeni syndrome
  Myelodysplastic syndrome
  Neoplasm
  Obesity
  Thrombocytopenia
  Pituitary gigantism
  Type-1/2 diabetes
  Hereditary thrombocytopenia and hematologic cancer predisposition syndrome
  Obsolete autosomal thrombocytopenia with normal platelets
  Leukemia
• UniProt ID: ANR26_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF14915 ; PF12001
• Sequence:
  MKKIFSKKGESPLGSFARRQRSSAGGGGEPGEGAYSQPGYHVRDRDLGKIHKAASAGNVA
  KVQQILLLRKNGLNDRDKMNRTALHLACANGHPEVVTLLVDRKCQLNVCDNENRTALMKA
  VQCQEEKCATILLEHGADPNLADVHGNTALHYAVYNEDISVATKLLLYDANIEAKNKDDL
  TPLLLAVSGKKQQMVEFLIKKKANVNAVDKLESSHQLISEYKEERIPKHSSQNSNSVDES
  SEDSLSRLSGKPGVDDSWPTSDDEDLNFDTKNVPKPSLAKLMTASQQSRKNLEATYGTVR
  TGNRTLFEDRDSDSQDEVVVESLPTTSIKVQCFSHPTYQSPDLLPKPSHKSLANPGLMKE
  EPTKPGIAKKENGIDIIESAPLEQTNNDNLTYVDEVHKNNRSDMMSALGLGQEEDIESPW
  DSESISENFPQKYVDPLAGAADGKEKNIGNEQAEDVFYIPSCMSGSRNFKMAKLEDTRNV
  GMPVAHMESPERYLHLKPTIEMKDSVPNKAGGMKDVQTSKAAEHDLEVASEEEQEREGSE
  NNQPQVEEERKKHRNNEMEVSANIHDGATDDAEDDDDDDGLIQKRKSGETDHQQFPRKEN
  KEYASSGPALQMKEVKSTEKEKRTSKESVNSPVFGKASLLTGGLLQVDDDSSLSEIDEDE
  GRPTKKTSNEKNKVKNQIQSMDDVDDLTQSSETASEDCELPHSSYKNFMLLIEQLGMECK
  DSVSLLKIQDAALSCERLLELKKNHCELLTVKIKKMEDKVNVLQRELSETKEIKSQLEHQ
  KVEWERELCSLRFSLNQEEEKRRNADTLYEKIREQLRRKEEQYRKEVEVKQQLELSLQTL
  EMELRTVKSNLNQVVQERNDAQRQLSREQNARMLQDGILTNHLSKQKEIEMAQKKMNSEN
  SHSHEEEKDLSHKNSMLQEEIAMLRLEIDTIKNQNQEKEKKCFEDLKIVKEKNEDLQKTI
  KQNEETLTQTISQYNGRLSVLTAENAMLNSKLENEKQSKERLEAEVESYHSRLAAAIHDR
  DQSETSKRELELAFQRARDECSRLQDKMNFDVSNLKDNNEILSQQLFKTESKLNSLEIEF
  HHTRDALREKTLGLERVQKDLSQTQCQMKEMEQKYQNEQVKVNKYIGKQESVEERLSQLQ
  SENMLLRQQLDDAHNKADNKEKTVINIQDQFHAIVQKLQAESEKQSLLLEERNKELISEC
  NHLKERQYQYENEKAEREVVVRQLQQELADTLKKQSMSEASLEVTSRYRINLEDETQDLK
  KKLGQIRNQLQEAQDRHTEAVRCAEKMQDHKQKLEKDNAKLKVTVKKQMDKIEELQKNLL
  NANLSEDEKEQLKKLMELKQSLECNLDQEMKKNVELEREITGFKNLLKMTRKKLNEYENG
  EFSFHGDLKTSQFEMDIQINKLKHKIDDLTAELETAGSKCLHLDTKNQILQEELLSMKTV
  QKKCEKLQKNKKKLEQEVINLRSHIERNMVELGQVKQYKQEIEERARQEIAEKLKEVNLF
  LQAQAASQENLEQFRENNFASMKSQMELRIKDLESELSKIKTSQEDFNKTELEKYKQLYL
  EELKVRKSLSSKLTKTNERLAEVNTKLLVEKQQSRSLFTTLTTRPVMEPPCVGNLNNSLD
  LNRKLIPRENLVISTSNPRASNNSMENYLSKMQQELEKNITRELKEAAAELESGSIASPL
  GSTDESNLNQDLVWKASREYVQVLKKNYMI
• Function: Acts as a regulator of adipogenesis. Involved in the regulation of the feeding behavior.
• Reactome Pathway:
  RND2 GTPase cycle (R-HSA-9696270)
  RND1 GTPase cycle (R-HSA-9696273)
  RND3 GTPase cycle (R-HSA-9696264)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thrombocytopenia 2	DISBLVLV	Definitive	Autosomal dominant	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[2]
Acquired thrombocytopenia	DISXH01C	Strong	Genetic Variation	[3]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Autosomal dominant	[5]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[6]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Genetic Variation	[7]
Coagulation defect	DIS9X3H6	Strong	Genetic Variation	[8]
Gray platelet syndrome	DISLOTCW	Strong	Genetic Variation	[9]
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	DIS7XO1W	Strong	GermlineCausalMutation	[10]
leukaemia	DISS7D1V	Strong	Genetic Variation	[11]
Li-Fraumeni syndrome	DISR64XA	Strong	Genetic Variation	[6]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Posttranslational Modification	[12]
Thrombocytopenia	DISU61YW	Strong	Genetic Variation	[13]
Pituitary gigantism	DISIUHNT	moderate	Genetic Variation	[14]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[12]
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	DIS1HP20	Supportive	Autosomal dominant	[10]
Obsolete autosomal thrombocytopenia with normal platelets	DISHFIE8	Supportive	Autosomal dominant	[15]
Leukemia	DISNAKFL	Limited	Genetic Variation	[11]

10 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 Ankyrin repeat domain-containing protein 26 (ANKRD26).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[21]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[26]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the expression of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Ankyrin repeat domain-containing protein 26 (ANKRD26).	[22]

References

• [1] 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.
• [2] ANKRD26-RET - A novel gene fusion involving RET in papillary thyroid carcinoma.Cancer Genet. 2019 Oct;238:10-17. doi: 10.1016/j.cancergen.2019.07.002. Epub 2019 Jul 5.
• [3] Clinical and laboratory characteristics in congenital ANKRD26 mutation-associated thrombocytopenia: A detailed phenotypic study of a family.Platelets. 2016 Nov;27(7):712-715. doi: 10.3109/09537104.2016.1171305. Epub 2016 Apr 28.
• [4] Inherited thrombocytopenias frequently diagnosed in adults.J Thromb Haemost. 2013 Jun;11(6):1006-19. doi: 10.1111/jth.12196.
• [5] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [6] Hereditary myeloid malignancies.Best Pract Res Clin Haematol. 2019 Jun;32(2):163-176. doi: 10.1016/j.beha.2019.05.001. Epub 2019 May 3.
• [7] Inherited thrombocytopenia caused by ANKRD26 mutations misdiagnosed and treated as myelodysplastic syndrome: report on two cases.J Thromb Haemost. 2017 Dec;15(12):2388-2392. doi: 10.1111/jth.13855. Epub 2017 Oct 28.
• [8] Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families.Blood. 2011 Jun 16;117(24):6673-80. doi: 10.1182/blood-2011-02-336537. Epub 2011 Apr 5.
• [9] Thrombocytopenias due to gray platelet syndrome or THC2 mutations.Semin Thromb Hemost. 2011 Sep;37(6):690-7. doi: 10.1055/s-0031-1291379. Epub 2011 Nov 18.
• [10] A novel ANKRD26 gene variant causing inherited thrombocytopenia in a family of Finnish origin: Another brick in the wall?. Thromb Res. 2017 Mar;151:41-43. doi: 10.1016/j.thromres.2017.01.001. Epub 2017 Jan 10.
• [11] Thrombocytopenia-associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation.J Clin Invest. 2014 Feb;124(2):580-91. doi: 10.1172/JCI71861. Epub 2014 Jan 16.
• [12] Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity.Clin Epigenetics. 2019 Dec 4;11(1):181. doi: 10.1186/s13148-019-0768-0.
• [13] Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.
• [14] A model for obesity and gigantism due to disruption of the Ankrd26 gene.Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):270-5. doi: 10.1073/pnas.0710978105. Epub 2007 Dec 27.
• [15] Analyses of Genetic and Clinical Parameters for Screening Patients With Inherited Thrombocytopenia with Small or Normal-Sized Platelets. Pediatr Blood Cancer. 2015 Dec;62(12):2082-8. doi: 10.1002/pbc.25668. Epub 2015 Jul 14.
• [16] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [17] 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.
• [18] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [19] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [20] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [21] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] Immunoselection and characterization of a human genomic PPAR binding fragment located within POTE genes. Biochimie. 2007 Mar;89(3):329-36. doi: 10.1016/j.biochi.2006.09.017. Epub 2006 Oct 18.