Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJXYAE5)

• DOT Name: Ankyrin repeat domain-containing protein 30A (ANKRD30A)
• Synonyms: Serologically defined breast cancer antigen NY-BR-1
• Gene Name: ANKRD30A
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Prostate neoplasm
  Ankylosing spondylitis
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Autoimmune thyroid disease
  Coeliac disease
  Common variable immunodeficiency
  Crohn disease
  Juvenile idiopathic arthritis
  Psoriasis
  STAT3-related early-onset multisystem autoimmune disease
  Systemic lupus erythematosus
  Type-1 diabetes
  Ulcerative colitis
  Epithelial ovarian cancer
  Breast neoplasm
  Invasive breast carcinoma
  Male breast carcinoma
• UniProt ID: AN30A_HUMAN
• PDB ID: 6R2L
• Pfam ID: PF12796 ; PF14915
• Sequence:
  MEEISAAAVKVVPGPERPSPFSQLVYTSNDSYIVHSGDLRKIHKAASRGQVRKLEKMTKR
  KKTINLNIQDAQKRTALHWACVNGHEEVVTFLVDRKCQLDVLDGEHRTPLMKALQCHQEA
  CANILIDSGADINLVDVYGNTALHYAVYSEILSVVAKLLSHGAVIEVHNKASLTPLLLSI
  TKRSEQIVEFLLIKNANANAVNKYKCTALMLAVCHGSSEIVGMLLQQNVDVFAADICGVT
  AEHYAVTCGFHHIHEQIMEYIRKLSKNHQNTNPEGTSAGTPDEAAPLAERTPDTAESLVE
  KTPDEAAPLVERTPDTAESLVEKTPDEAASLVEGTSDKIQCLEKATSGKFEQSAEETPRE
  ITSPAKETSEKFTWPAKGRPRKIAWEKKEDTPREIMSPAKETSEKFTWAAKGRPRKIAWE
  KKETPVKTGCVARVTSNKTKVLEKGRSKMIACPTKESSTKASANDQRFPSESKQEEDEEY
  SCDSRSLFESSAKIQVCIPESIYQKVMEINREVEEPPKKPSAFKPAIEMQNSVPNKAFEL
  KNEQTLRADPMFPPESKQKDYEENSWDSESLCETVSQKDVCLPKATHQKEIDKINGKLEE
  SPNKDGLLKATCGMKVSIPTKALELKDMQTFKAEPPGKPSAFEPATEMQKSVPNKALELK
  NEQTLRADEILPSESKQKDYEENSWDTESLCETVSQKDVCLPKAAHQKEIDKINGKLEGS
  PVKDGLLKANCGMKVSIPTKALELMDMQTFKAEPPEKPSAFEPAIEMQKSVPNKALELKN
  EQTLRADEILPSESKQKDYEESSWDSESLCETVSQKDVCLPKATHQKEIDKINGKLEESP
  DNDGFLKAPCRMKVSIPTKALELMDMQTFKAEPPEKPSAFEPAIEMQKSVPNKALELKNE
  QTLRADQMFPSESKQKKVEENSWDSESLRETVSQKDVCVPKATHQKEMDKISGKLEDSTS
  LSKILDTVHSCERARELQKDHCEQRTGKMEQMKKKFCVLKKKLSEAKEIKSQLENQKVKW
  EQELCSVRLTLNQEEEKRRNADILNEKIREELGRIEEQHRKELEVKQQLEQALRIQDIEL
  KSVESNLNQVSHTHENENYLLHENCMLKKEIAMLKLEIATLKHQYQEKENKYFEDIKILK
  EKNAELQMTLKLKEESLTKRASQYSGQLKVLIAENTMLTSKLKEKQDKEILEAEIESHHP
  RLASAVQDHDQIVTSRKSQEPAFHIAGDACLQRKMNVDVSSTIYNNEVLHQPLSEAQRKS
  KSLKINLNYAGDALRENTLVSEHAQRDQRETQCQMKEAEHMYQNEQDNVNKHTEQQESLD
  QKLFQLQSKNMWLQQQLVHAHKKADNKSKITIDIHFLERKMQHHLLKEKNEEIFNYNNHL
  KNRIYQYEKEKAETENS
• Tissue Specificity: Mainly expressed in breast and testis. A very faint signal is detected in placenta. Also expressed in many breast cancer cells.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Biomarker	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[5]
Ankylosing spondylitis	DISRC6IR	moderate	Genetic Variation	[6]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[6]
Autoimmune disease, susceptibility to, 6	DISHNUXI	moderate	Genetic Variation	[6]
Autoimmune thyroid disease	DISIHC6A	moderate	Genetic Variation	[6]
Coeliac disease	DISIY60C	moderate	Genetic Variation	[6]
Common variable immunodeficiency	DISHE7JQ	moderate	Genetic Variation	[6]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[6]
Juvenile idiopathic arthritis	DISQZGBV	moderate	Genetic Variation	[6]
Psoriasis	DIS59VMN	moderate	Genetic Variation	[6]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	moderate	Genetic Variation	[6]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[6]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[6]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[6]
Epithelial ovarian cancer	DIS56MH2	Disputed	Genetic Variation	[7]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[8]
Invasive breast carcinoma	DISANYTW	Limited	Biomarker	[9]
Male breast carcinoma	DISUNQ2Q	Limited	Biomarker	[4]

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 Ankyrin repeat domain-containing protein 30A (ANKRD30A).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ankyrin repeat domain-containing protein 30A (ANKRD30A).	[13]

4 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 30A (ANKRD30A).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Ankyrin repeat domain-containing protein 30A (ANKRD30A).	[12]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the expression of Ankyrin repeat domain-containing protein 30A (ANKRD30A).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ankyrin repeat domain-containing protein 30A (ANKRD30A).	[12]

References

• [1] Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1 in normal breast, testis and their malignant counterparts.Int J Cancer. 2008 Apr 1;122(7):1585-91. doi: 10.1002/ijc.23241.
• [2] A transplantable tumor model allowing investigation of NY-BR-1-specific T cell responses in HLA-DRB1*0401 transgenic mice.BMC Cancer. 2019 Sep 13;19(1):914. doi: 10.1186/s12885-019-6102-6.
• [3] Immunohistochemical Analysis of the Expression of Breast Markers in Basal-like Breast Carcinomas Defined as Triple Negative Cancers Expressing Keratin 5.Pathol Oncol Res. 2018 Apr;24(2):259-267. doi: 10.1007/s12253-017-0246-y. Epub 2017 May 3.
• [4] Preferential expression of NY-BR-1 and GATA-3 in male breast cancer.J Cancer Res Clin Oncol. 2018 Feb;144(2):199-204. doi: 10.1007/s00432-017-2542-z. Epub 2017 Nov 7.
• [5] Humoral and cellular immune responses against the breast cancer antigen NY-BR-1: definition of two HLA-A2 restricted peptide epitopes.Cancer Immun. 2005 Dec 12;5:11.
• [6] Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.Nat Med. 2015 Sep;21(9):1018-27. doi: 10.1038/nm.3933. Epub 2015 Aug 24.
• [7] Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women.Nat Commun. 2014 Aug 19;5:4682. doi: 10.1038/ncomms5682.
• [8] In silico SNP analysis of the breast cancer antigen NY-BR-1.BMC Cancer. 2016 Nov 18;16(1):901. doi: 10.1186/s12885-016-2924-7.
• [9] Preferential nuclear and cytoplasmic NY-BR-1 protein expression in primary breast cancer and lymph node metastases.Clin Cancer Res. 2006 May 1;12(9):2745-51. doi: 10.1158/1078-0432.CCR-05-2192.
• [10] 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.
• [11] 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.
• [12] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [13] 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.
• [14] 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.