Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1MREUS)

• DOT Name: Ankyrin repeat and SAM domain-containing protein 4B (ANKS4B)
• Synonyms: Harmonin-interacting ankyrin repeat-containing protein; Harp
• Gene Name: ANKS4B
• Related Disease:
  Schimke immuno-osseous dysplasia
  Adult glioblastoma
  Adult respiratory distress syndrome
  Benign prostatic hyperplasia
  Cervical Intraepithelial neoplasia
  Glioblastoma multiforme
  Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration
  Neoplasm
  Pantothenate kinase-associated neurodegeneration
  Prostate cancer
  Prostate carcinoma
• UniProt ID: ANS4B_HUMAN
• Pfam ID: PF12796 ; PF00536
• Sequence:
  MSTRYHQAASDSYLELLKEATKRDLNLSDEDGMTPTLLAAYHGNLEALEIICSRGGDPDR
  CDIWGNTPLHFAASNGHAHCVSFLVNFGANIFALDNDLQTPLDAAASREQNECVALLDKA
  ATAQNIMNPKKVTRLKEQAQKNARRQIKECERLQEKHQNKMAHTYSKEESGTLSSSKGTF
  SRSSPSNASAPGTFGSLSKGIKDTFKIKFKKNKDTAEQVGKEGRSGQRNVMEVFREEEED
  SFSGDFKEKLQLSAEEDGSVHHESILNRPGLGSIVFRRNRISSPEDISDSKREFGFKLPS
  ELLQRQGASEADEGAADEEGEENGLKDDLPWDDDEVEWEEDVVDATPLEVFLLSQHLEEF
  LPIFKREQIDLEALLLCSDEDLQSIQMQLGPRKKVLNAINRRKQVLQQPGQLVDTSL
• Function: As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length. Plays a role in assembly of the complex. May play a role in cellular response to endoplasmic reticulum stress.
• Tissue Specificity: Expressed in kidney and small intestine.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schimke immuno-osseous dysplasia	DISGEL3Z	Definitive	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[3]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[4]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Genetic Variation	[5]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration	DISBN8XM	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Pantothenate kinase-associated neurodegeneration	DIS50V55	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]

7 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 and SAM domain-containing protein 4B (ANKS4B).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ankyrin repeat and SAM domain-containing protein 4B (ANKS4B).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ankyrin repeat and SAM domain-containing protein 4B (ANKS4B).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ankyrin repeat and SAM domain-containing protein 4B (ANKS4B).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ankyrin repeat and SAM domain-containing protein 4B (ANKS4B).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ankyrin repeat and SAM domain-containing protein 4B (ANKS4B).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Ankyrin repeat and SAM domain-containing protein 4B (ANKS4B).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ankyrin repeat and SAM domain-containing protein 4B (ANKS4B).	[12]

References

• [1] Annealing helicase HARP closes RPA-stabilized DNA bubbles non-processively.Nucleic Acids Res. 2017 May 5;45(8):4687-4695. doi: 10.1093/nar/gkx147.
• [2] HARP111-136 enhances radiation-induced apoptosis of U87MG glioblastoma by induction of the proapoptotic protein CHOP.Int J Oncol. 2011 Jan;38(1):179-88.
• [3] Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial.Lancet Respir Med. 2018 Sep;6(9):691-698. doi: 10.1016/S2213-2600(18)30177-2. Epub 2018 Aug 2.
• [4] Involvement of heparin affin regulatory peptide in human prostate cancer.Prostate. 1999 Feb 1;38(2):126-36. doi: 10.1002/(sici)1097-0045(19990201)38:2<126::aid-pros6>3.0.co;2-c.
• [5] Cervical intraepithelial neoplasia (CIN) in African women living with HIV: role and effect of rigorous histopathological review by a panel of pathologists in the HARP study endpoint determination.J Clin Pathol. 2018 Jan;71(1):40-45. doi: 10.1136/jclinpath-2017-204512. Epub 2017 Jun 9.
• [6] HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. Neurology. 2002 Jun 11;58(11):1673-4. doi: 10.1212/wnl.58.11.1673.
• [7] 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.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.