Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT62KZII)

• DOT Name: Ankyrin repeat domain-containing protein 55 (ANKRD55)
• Gene Name: ANKRD55
• Related Disease:
  Alzheimer disease
  Autoimmune disease
  Dermatomyositis
  Multiple sclerosis
  Non-insulin dependent diabetes
  Post-traumatic stress disorder
  Psoriasis
  Acute myelogenous leukaemia
  Autoimmune disease, susceptibility to, 6
  Autoimmune thyroid disease
  Coeliac disease
  Common variable immunodeficiency
  Immune system disorder
  Inflammatory bowel disease
  STAT3-related early-onset multisystem autoimmune disease
  Systemic lupus erythematosus
  Type-1 diabetes
  Ankylosing spondylitis
  Crohn disease
  Juvenile idiopathic arthritis
  Nervous system inflammation
  Rheumatoid arthritis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: ANR55_HUMAN
• Pfam ID: PF00023 ; PF12796
• Sequence:
  MMRQATMDFSTPSVFDQQRGDSSEEVDLTMVYQAASNGDVNALTAVIREDPSILECCDSE
  GCTPLMHAVSGRQADTVKLLLKMGANINMQDAYGRTSLCLATYLGWLEGCVSLLRNGAKH
  NIPDKNGRLPLHAATAEPDMRLLTVLLQQSNISEINHQDNEGMTPLHWAAFHNQPQHTQM
  LLKKGADPTLVDKDFKTALHWAVQSGNRILCSIILSHHQGPSIINYDDESGKTCVHIAAA
  AGFSDIIHELARVPECNLQALDVDDRTPLHWAAAAGKAECVQSLLELGMDSNLRDINEST
  PLAYALYCGHTACVKLLSQESRTEPTRPPPSQSSRPQKKERRFNVLNQIFCKNKKEEQRA
  HQKDPSRDRYREEDTSEVNDIITTFDSIVGTNCQEQPGDQVAMVEFKKKTSDNSKYLLPE
  KKPLARKGLPPIRTQSLPPITLGNNFLTASHRATSHAGLSSAPHHMAQRSQKSRSEQDLL
  NNRTGCQMLLDNPWKSDSNQVFSYKVWTVSSSDKLLDRLLSVRPGHQEVSVPPHLRHLHN
  PSSGQNFQHLSPNRHKIRDLPFTRNNLAPLPDQKFLSGEPLRTNRVLPAIPSQRRHSTAA
  EESEHSANPTSDEN

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[2]
Dermatomyositis	DIS50C5O	Strong	Altered Expression	[3]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[4]
Post-traumatic stress disorder	DISHL1EY	Strong	Genetic Variation	[5]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[6]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[7]
Autoimmune disease, susceptibility to, 6	DISHNUXI	moderate	Genetic Variation	[8]
Autoimmune thyroid disease	DISIHC6A	moderate	Genetic Variation	[8]
Coeliac disease	DISIY60C	moderate	Genetic Variation	[8]
Common variable immunodeficiency	DISHE7JQ	moderate	Genetic Variation	[8]
Immune system disorder	DISAEGPH	moderate	Genetic Variation	[9]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[10]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	moderate	Genetic Variation	[8]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[8]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[8]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[6]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[6]
Juvenile idiopathic arthritis	DISQZGBV	Limited	Biomarker	[11]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[13]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[6]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[14]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ankyrin repeat domain-containing protein 55 (ANKRD55).	[21]

References

• [1] Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
• [2] Interactome of the Autoimmune Risk Protein ANKRD55.Front Immunol. 2019 Sep 18;10:2067. doi: 10.3389/fimmu.2019.02067. eCollection 2019.
• [3] T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients.Arthritis Res Ther. 2018 Aug 29;20(1):188. doi: 10.1186/s13075-018-1688-7.
• [4] Replication Study in a Japanese Population to Evaluate the Association between 10 SNP Loci, Identified in European Genome-Wide Association Studies, and Type 2 Diabetes.PLoS One. 2015 May 7;10(5):e0126363. doi: 10.1371/journal.pone.0126363. eCollection 2015.
• [5] Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers.JAMA Psychiatry. 2016 Jul 1;73(7):695-704. doi: 10.1001/jamapsychiatry.2016.0350.
• [6] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [7] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [8] 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.
• [9] Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.PLoS Genet. 2011 Feb;7(2):e1002004. doi: 10.1371/journal.pgen.1002004. Epub 2011 Feb 24.
• [10] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [11] CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic arthritis.Ann Rheum Dis. 2015 Dec;74(12):2193-8. doi: 10.1136/annrheumdis-2013-205138. Epub 2014 Jul 23.
• [12] Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55.J Immunol. 2016 Jun 1;196(11):4553-65. doi: 10.4049/jimmunol.1501205. Epub 2016 May 4.
• [13] Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
• [14] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] 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.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] 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.
• [19] 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.
• [20] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [21] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [22] 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.