Details of Drug Off-Target (DOT)

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

DOT Name Ankyrin repeat and SAM domain-containing protein 3 (ANKS3)
Gene Name ANKS3
Related Disease
Episodic kinesigenic dyskinesia 1 ( )
Nephronophthisis ( )
Normal pressure hydrocephalus ( )
Situs inversus ( )
Laterality defects, autosomal dominant ( )
UniProt ID
ANKS3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4NJ8; 4NL9
Pfam ID
PF12796 ; PF13637 ; PF00536
Sequence
MSELSDEASEPELLNRSLSMWHGLGTQVSGEELDVPLDLHTAASIGQYEVVKECVQRREL
DLNKKNGGGWTPLMYASYIGHDTIVHLLLEAGVSVNVPTPEGQTPLMLASSCGNESIAYF
LLQQGAELEMKDIQGWTALFHCTSAGHQHMVRFLLDSGANANVREPICGFTPLMEAAAAG
HEIIVQYFLNHGVKVDARDHSGATARMLAKQYGHMKIVALMDTYSPSLPKSLYRSPEKYE
DLSSSDESCPAPQRQRPCRKKGVSIHEGPRALARITGIGLGGRAPRPRYEQAPPRGYVTF
NSSGENPLEEEGLCCRDVTSPINERDVESSSSSSSREEHAFCANLGPVQSSSSSEGLARA
QGLSSEASVESNEDSDHACKSSARKQAKSYMKTKNPDSQWPPRAATDREGFLAESSPQTQ
RAPYSGPQDLAALLEQIGCLKYLQVFEEQDVDLRIFLTLTESDLKEIGITLFGPKRKMTS
AIARWHSSARPPGDALELAYADRLEAEMQELAIQLHKRCEEVEATRGQVCQEQELRAVVE
SCLLEQDRAREDLQARLRETWALARDAALVLDQLRACQAELSSRVRQDQPPGAATLGLAV
PPADSKGWQASLQAMSLPELSGALEDRVREMGQALCLVTQSLEKLQVLNGKKWRET
Function May be involved in vasopressin signaling in the kidney.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Episodic kinesigenic dyskinesia 1 DISGVQMP Strong Genetic Variation [1]
Nephronophthisis DISXU4HY Strong Biomarker [2]
Normal pressure hydrocephalus DISOEFO9 Strong Genetic Variation [3]
Situs inversus DISFA7AJ Supportive Autosomal dominant [4]
Laterality defects, autosomal dominant DISFIR5T Limited Autosomal recessive [5]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 and SAM domain-containing protein 3 (ANKS3). [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Ankyrin repeat and SAM domain-containing protein 3 (ANKS3). [7]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Ankyrin repeat and SAM domain-containing protein 3 (ANKS3). [9]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Ankyrin repeat and SAM domain-containing protein 3 (ANKS3). [8]
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References

1 The SAM domain of ANKS6 has different interacting partners and mutations can induce different cystic phenotypes.Kidney Int. 2015 Aug;88(2):299-310. doi: 10.1038/ki.2015.122. Epub 2015 Jun 3.
2 Metabolic Phenotyping of Anks3 Depletion in mIMCD-3 cells - a Putative Nephronophthisis Candidate.Sci Rep. 2018 Jun 13;8(1):9022. doi: 10.1038/s41598-018-27389-y.
3 Anks3 interacts with nephronophthisis proteins and is required for normal renal development.Kidney Int. 2015 Jun;87(6):1191-200. doi: 10.1038/ki.2015.17. Epub 2015 Feb 11.
4 ANKS3 is mutated in a family with autosomal recessive laterality defect. Hum Genet. 2016 Nov;135(11):1233-1239. doi: 10.1007/s00439-016-1712-4. Epub 2016 Jul 14.
5 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
6 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.
7 Locus-Specific Differential DNA Methylation and Urinary Arsenic: An Epigenome-Wide Association Study in Blood among Adults with Low-to-Moderate Arsenic Exposure. Environ Health Perspect. 2020 Jun;128(6):67015. doi: 10.1289/EHP6263. Epub 2020 Jun 30.
8 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
9 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.